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Studies address ibrutinib bleeding risk in patients with CLL receiving Mohs surgery
Patients receiving , new research shows.
“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.
“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).
With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.
While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.
In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.
However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.
The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.
The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).
Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.
In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.
“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.
In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).
Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).
There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).
In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”
Holding treatment
To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”
“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.
Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.
The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.
The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.
“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.
“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.
She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.
“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”
Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients receiving , new research shows.
“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.
“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).
With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.
While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.
In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.
However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.
The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.
The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).
Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.
In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.
“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.
In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).
Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).
There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).
In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”
Holding treatment
To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”
“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.
Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.
The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.
The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.
“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.
“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.
She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.
“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”
Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients receiving , new research shows.
“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.
“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).
With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.
While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.
In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.
However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.
The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.
The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).
Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.
In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.
“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.
In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).
Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).
There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).
In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”
Holding treatment
To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”
“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.
Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.
The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.
The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.
“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.
“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.
She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.
“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”
Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE ACMS ANNUAL MEETING
Dodging potholes from cancer care to hospice transitions
I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.
Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.
Transitioning from active therapy to symptom management
Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.
The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones.
When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.
In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.
A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
‘Don’t just put in the hospice order and walk away’
Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.
First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.
Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.
If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.
These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.
As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.
Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.
Transitioning from active therapy to symptom management
Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.
The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones.
When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.
In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.
A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
‘Don’t just put in the hospice order and walk away’
Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.
First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.
Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.
If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.
These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.
As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.
Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.
Transitioning from active therapy to symptom management
Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.
The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones.
When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.
In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.
A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
‘Don’t just put in the hospice order and walk away’
Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.
First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.
Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.
If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.
These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.
As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.
Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.
Novel COVID-19 vaccine could fill the void for patients with blood cancers
according to study results presented at the annual meeting of the American Association for Cancer Research.
The phase 1/2 trial included 54 patients with a B-cell deficiency (mean age, 63 years; 28% female): 4 had congenital B-cell deficiency and 50 had a blood cancer (lymphocytic leukemia or lymphoma). T-cell immune responses were observed in 86% of patients 28 days after vaccination with a single CoVac-1 dose. The potency of CoVac-1–induced T-cell responses exceeded those seen typically with B cell–deficient patient responses after mRNA vaccine treatment and were comparable with those seen among nonimmunocompromised COVID-19 patients.
In the majority of individuals, currently approved SARS-CoV-2 vaccines induce a robust immune response, however, their efficacy, has been shown to be decreased among individuals who are immunocompromised. Patients treated for hematologic cancers, in particular, receive treatment regimens that damage healthy immune cells, particularly B cells, said Juliane Walz, MD, the study’s senior author and professor of medicine at University Hospital Tübingen (Germany).
“In the clinic, we see many cancer patients who do not mount sufficient humoral immune responses after vaccination with available SARS-CoV-2 vaccines,” Dr. Walz said. “These patients are at a high risk for a severe course of COVID-19.”
B-cell deficiency, she stated, can be compensated for by enhancing T-cell responses against SARS-CoV-2, which can then combat infections in the absence of neutralizing antibodies.
In a prior study of CoVac-1 among 36 adults without immune deficiency, the vaccine elicited T-cell responses that were still robust 3 months post vaccination, and that included responses against omicron and other key SARS-CoV-2 variants.
While mRNA-based or adenoviral vector-based vaccines are limited to the spike protein and are thus prone to loss of activity because of viral mutations, CoVac-1–induced T-cell immunity is far more intense and broader, Dr. Walz said.
CoVac-1 is a peptide vaccine that is injected directly rather than being encoded via mRNA and targets different viral components. It would not be given, however, to healthy, immunocompetent adults because it is important for them to have both B-cell antibody and T-cell response.
The patients with B-cell deficiency recruited for the study were given a single dose of CoVac-1 and assessed for safety and immunogenicity until day 56. Prior vaccinations with an approved SARS-CoV-2 vaccine had failed to elicit a humoral response in 87% of the subjects.
“Our vaccine does not induce antibody responses,” Dr. Walz said. “However, it could be used to induce broad T-cell responses as a complementary or additive vaccine for elderly adults. In the elderly, antibody responses decline very, very fast after vaccination.”
Dr. Walz said that CoVac-1 could find application in various syndromes associated with congenital B-cell deficiencies, in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, or diseases treated with rituximab or other B cell–depleting therapies (for example, ofatumumab, blinatumomab, or chimeric antigen receptor T cells), and in transplant patients.
A phase 3 study of CoVac-1 versus placebo is under discussion and would require about 300-500 subjects, Dr. Walz said.
“CoVac-1 is designed to induce broad and long-lasting SARS-CoV-2 T-cell immunity, even in individuals who have impaired ability to mount sufficient immunity from a currently approved vaccine, and thus protect these high-risk patients from a severe course of COVID-19,” Dr. Walz said.
“Having an option for these patients is just critical – so this is significant work,” said Ana Maria Lopez, MD, MPH, of the Sidney Kimmel Cancer Center–Jefferson Health, Philadelphia.
Limitations of this study included the small sample size with low racial and ethnic diversity, Dr. Walz stated.
Funding was provided by the Ministry of Science, Research and the Arts of the state of Baden-Württemberg; the Federal Ministry of Research and Education in Germany; the German Research Foundation under Germany’s Excellence Strategy; and the Clinical Cooperation Unit Translational Immunology at University Hospital Tübingen. Dr. Walz holds the CoVac-1 patent.
according to study results presented at the annual meeting of the American Association for Cancer Research.
The phase 1/2 trial included 54 patients with a B-cell deficiency (mean age, 63 years; 28% female): 4 had congenital B-cell deficiency and 50 had a blood cancer (lymphocytic leukemia or lymphoma). T-cell immune responses were observed in 86% of patients 28 days after vaccination with a single CoVac-1 dose. The potency of CoVac-1–induced T-cell responses exceeded those seen typically with B cell–deficient patient responses after mRNA vaccine treatment and were comparable with those seen among nonimmunocompromised COVID-19 patients.
In the majority of individuals, currently approved SARS-CoV-2 vaccines induce a robust immune response, however, their efficacy, has been shown to be decreased among individuals who are immunocompromised. Patients treated for hematologic cancers, in particular, receive treatment regimens that damage healthy immune cells, particularly B cells, said Juliane Walz, MD, the study’s senior author and professor of medicine at University Hospital Tübingen (Germany).
“In the clinic, we see many cancer patients who do not mount sufficient humoral immune responses after vaccination with available SARS-CoV-2 vaccines,” Dr. Walz said. “These patients are at a high risk for a severe course of COVID-19.”
B-cell deficiency, she stated, can be compensated for by enhancing T-cell responses against SARS-CoV-2, which can then combat infections in the absence of neutralizing antibodies.
In a prior study of CoVac-1 among 36 adults without immune deficiency, the vaccine elicited T-cell responses that were still robust 3 months post vaccination, and that included responses against omicron and other key SARS-CoV-2 variants.
While mRNA-based or adenoviral vector-based vaccines are limited to the spike protein and are thus prone to loss of activity because of viral mutations, CoVac-1–induced T-cell immunity is far more intense and broader, Dr. Walz said.
CoVac-1 is a peptide vaccine that is injected directly rather than being encoded via mRNA and targets different viral components. It would not be given, however, to healthy, immunocompetent adults because it is important for them to have both B-cell antibody and T-cell response.
The patients with B-cell deficiency recruited for the study were given a single dose of CoVac-1 and assessed for safety and immunogenicity until day 56. Prior vaccinations with an approved SARS-CoV-2 vaccine had failed to elicit a humoral response in 87% of the subjects.
“Our vaccine does not induce antibody responses,” Dr. Walz said. “However, it could be used to induce broad T-cell responses as a complementary or additive vaccine for elderly adults. In the elderly, antibody responses decline very, very fast after vaccination.”
Dr. Walz said that CoVac-1 could find application in various syndromes associated with congenital B-cell deficiencies, in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, or diseases treated with rituximab or other B cell–depleting therapies (for example, ofatumumab, blinatumomab, or chimeric antigen receptor T cells), and in transplant patients.
A phase 3 study of CoVac-1 versus placebo is under discussion and would require about 300-500 subjects, Dr. Walz said.
“CoVac-1 is designed to induce broad and long-lasting SARS-CoV-2 T-cell immunity, even in individuals who have impaired ability to mount sufficient immunity from a currently approved vaccine, and thus protect these high-risk patients from a severe course of COVID-19,” Dr. Walz said.
“Having an option for these patients is just critical – so this is significant work,” said Ana Maria Lopez, MD, MPH, of the Sidney Kimmel Cancer Center–Jefferson Health, Philadelphia.
Limitations of this study included the small sample size with low racial and ethnic diversity, Dr. Walz stated.
Funding was provided by the Ministry of Science, Research and the Arts of the state of Baden-Württemberg; the Federal Ministry of Research and Education in Germany; the German Research Foundation under Germany’s Excellence Strategy; and the Clinical Cooperation Unit Translational Immunology at University Hospital Tübingen. Dr. Walz holds the CoVac-1 patent.
according to study results presented at the annual meeting of the American Association for Cancer Research.
The phase 1/2 trial included 54 patients with a B-cell deficiency (mean age, 63 years; 28% female): 4 had congenital B-cell deficiency and 50 had a blood cancer (lymphocytic leukemia or lymphoma). T-cell immune responses were observed in 86% of patients 28 days after vaccination with a single CoVac-1 dose. The potency of CoVac-1–induced T-cell responses exceeded those seen typically with B cell–deficient patient responses after mRNA vaccine treatment and were comparable with those seen among nonimmunocompromised COVID-19 patients.
In the majority of individuals, currently approved SARS-CoV-2 vaccines induce a robust immune response, however, their efficacy, has been shown to be decreased among individuals who are immunocompromised. Patients treated for hematologic cancers, in particular, receive treatment regimens that damage healthy immune cells, particularly B cells, said Juliane Walz, MD, the study’s senior author and professor of medicine at University Hospital Tübingen (Germany).
“In the clinic, we see many cancer patients who do not mount sufficient humoral immune responses after vaccination with available SARS-CoV-2 vaccines,” Dr. Walz said. “These patients are at a high risk for a severe course of COVID-19.”
B-cell deficiency, she stated, can be compensated for by enhancing T-cell responses against SARS-CoV-2, which can then combat infections in the absence of neutralizing antibodies.
In a prior study of CoVac-1 among 36 adults without immune deficiency, the vaccine elicited T-cell responses that were still robust 3 months post vaccination, and that included responses against omicron and other key SARS-CoV-2 variants.
While mRNA-based or adenoviral vector-based vaccines are limited to the spike protein and are thus prone to loss of activity because of viral mutations, CoVac-1–induced T-cell immunity is far more intense and broader, Dr. Walz said.
CoVac-1 is a peptide vaccine that is injected directly rather than being encoded via mRNA and targets different viral components. It would not be given, however, to healthy, immunocompetent adults because it is important for them to have both B-cell antibody and T-cell response.
The patients with B-cell deficiency recruited for the study were given a single dose of CoVac-1 and assessed for safety and immunogenicity until day 56. Prior vaccinations with an approved SARS-CoV-2 vaccine had failed to elicit a humoral response in 87% of the subjects.
“Our vaccine does not induce antibody responses,” Dr. Walz said. “However, it could be used to induce broad T-cell responses as a complementary or additive vaccine for elderly adults. In the elderly, antibody responses decline very, very fast after vaccination.”
Dr. Walz said that CoVac-1 could find application in various syndromes associated with congenital B-cell deficiencies, in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, or diseases treated with rituximab or other B cell–depleting therapies (for example, ofatumumab, blinatumomab, or chimeric antigen receptor T cells), and in transplant patients.
A phase 3 study of CoVac-1 versus placebo is under discussion and would require about 300-500 subjects, Dr. Walz said.
“CoVac-1 is designed to induce broad and long-lasting SARS-CoV-2 T-cell immunity, even in individuals who have impaired ability to mount sufficient immunity from a currently approved vaccine, and thus protect these high-risk patients from a severe course of COVID-19,” Dr. Walz said.
“Having an option for these patients is just critical – so this is significant work,” said Ana Maria Lopez, MD, MPH, of the Sidney Kimmel Cancer Center–Jefferson Health, Philadelphia.
Limitations of this study included the small sample size with low racial and ethnic diversity, Dr. Walz stated.
Funding was provided by the Ministry of Science, Research and the Arts of the state of Baden-Württemberg; the Federal Ministry of Research and Education in Germany; the German Research Foundation under Germany’s Excellence Strategy; and the Clinical Cooperation Unit Translational Immunology at University Hospital Tübingen. Dr. Walz holds the CoVac-1 patent.
FROM AACR 2022
Few new cancer drugs replace current standards of care
, a new analysis shows.
Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.
“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”
The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.
To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.
The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.
Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.
A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.
Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.
A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.
Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.
The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).
The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”
The study was funded by a grant from Arnold Ventures.
A version of this article first appeared on Medscape.com.
, a new analysis shows.
Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.
“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”
The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.
To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.
The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.
Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.
A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.
Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.
A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.
Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.
The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).
The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”
The study was funded by a grant from Arnold Ventures.
A version of this article first appeared on Medscape.com.
, a new analysis shows.
Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.
“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”
The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.
To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.
The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.
Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.
A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.
Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.
A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.
Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.
The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).
The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”
The study was funded by a grant from Arnold Ventures.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Eating olive oil may slow CLL disease progression
Olive oil is a major component of the Mediterranean diet, and olive phenols have been shown to convey antioxidant, anti-inflammatory, anticancer, neuroprotective, and antidiabetic effects by modulating various molecular pathways, Andrea Paola Rojas Gil, PhD, of the University of Peloponnese, Tripoli, Greece, and colleagues wrote.
In most patients, CLL is incurable, but those at the early stages do not need immediate therapy and may benefit from an intervention to prevent disease progression, the authors wrote. Previous research suggested that dietary intervention exerts a salutary effect on early CLL, and in vitro studies suggested that oleocanthal, a component of extra virgin olive oil, induced anticancer activity.
In a study published in Frontiers in Oncology, the researchers enrolled adults with early stage CLL who had not undergone chemotherapy or other treatment. All patients adhered to a Mediterranean-style diet.
After a washout period of 9-12 months, the researchers randomized 22 patients to extra virgin olive oil high in oleocanthal and oleacein (high OC/OL-EVOO). Patients in the intervention group consumed 40 mL/day of high OC/OL-EVOO before meals. Their average age was 71 years; 10 were women and 12 were men.
The primary outcomes included changes in hematological, biochemical, and apoptotic markers. After 6 months, patients in the intervention group showed a statistically significant reduction in white blood cells and lymphocyte count, compared with measurements taken 3 months before the intervention. The WBC decrease was greatest among patients with the highest WBC levels at baseline.
As for biochemical markers, the researchers observed a significant decrease in glucose levels during the intervention, but no significant effects on metabolic indexes or renal function.
After 3 months and also after 6 months of the olive oil intervention, patients showed a significant increase in the apoptotic markers ccK18 and Apo1-Fas (P ≤ .05 for both), as well as an increase in the cell cycle negative regulator p21. The dietary intervention also was associated with significant decreases in expression of the antiapoptotic protein survivin and in cyclin D, a positive cell cycle regulator protein.
Further, patients who had a high ccK18 level at baseline showed a significantly greater increase in ccK18 after the intervention, compared with those with lower ccK18 at baseline (P = .001).
Notably, “a negative correlation of the WBC at the end of the dietary intervention with the fluctuation of the protein expression of the apoptotic marker ccK18 (final – initial) was observed,” the researchers wrote in their discussion.
The study findings were limited by several factors including the small sample size, short intervention time, and pilot design, the researchers said. Other limitations include the possible effect of other unmeasured properties of olive oil.
However, the results reflect previous studies showing the benefits of a Mediterranean-type diet, and they represent the first clinical trial to indicate possible beneficial effects from oleocanthal and oleacein on the progression of CLL. Therefore, the authors concluded, the study is worthy of a large, multicenter trial.
Pilot data merit more research
In an interview, corresponding author Prokopios Magiatis, PhD, noted that CLL is “the most commonly diagnosed adult leukemia in Western countries and is responsible for about one in four cases of all leukemias.” CLL remains incurable in most patients, and ways to delay disease progression are needed.
“Oleocanthal is the active ingredient of early harvest olive oil with proven anticancer activities in vitro and in vivo,” Dr. Magiatis explained. “For this reason, it was a unique challenge to investigate the anticancer activity of this compound for the first time in humans through the dietary consumption of specifically selected olive oil.” He expressed surprise at the beneficial effects of high-oleocanthal olive oil, not only to the white blood cells, but also to glucose levels.
“It seems that oleocanthal can activate mechanisms related to the apoptosis of cancer cells, and also mechanisms related to blood glucose regulation without affecting any normal cells of the body,” he said. “All anticancer drugs usually have severe side effects, however the administration of 25 mg of oleocanthal through the dietary consumption of olive oil did not present any harmful effects for at least 6 months of everyday use.
“The addition of naturally produced high-oleocanthal olive oil in the diet of early-stage CLL patients at a dose of three tablespoons per day [40 mL] is a practice that may lower the cancerous white blood cells of the patients without any risk,” said Dr. Magiatis. “High-oleocanthal early-harvest olive oil has been consumed for centuries, and may be the key of longevity of several Mediterranean populations.
“In our study, the number of the white blood cells returned back to the number it was one year before the initiation of the study; this clearly shows that it could be a significant factor for the delay of the progress of the disease,” he said.
The current trial was a pilot study in one hospital with only 22 patients for 6 months, said Dr. Magiatis. “We are currently preparing the expansion of the study to other hospitals and other countries, and we aim to include at least 100 patients for at least 1 year, to validate the already-obtained beneficial results.”
The clinical trial is supported by the nonprofit organization World Olive Center for Health, he added.
The current study received no outside funding. The researchers had no financial conflicts to disclose.
Olive oil is a major component of the Mediterranean diet, and olive phenols have been shown to convey antioxidant, anti-inflammatory, anticancer, neuroprotective, and antidiabetic effects by modulating various molecular pathways, Andrea Paola Rojas Gil, PhD, of the University of Peloponnese, Tripoli, Greece, and colleagues wrote.
In most patients, CLL is incurable, but those at the early stages do not need immediate therapy and may benefit from an intervention to prevent disease progression, the authors wrote. Previous research suggested that dietary intervention exerts a salutary effect on early CLL, and in vitro studies suggested that oleocanthal, a component of extra virgin olive oil, induced anticancer activity.
In a study published in Frontiers in Oncology, the researchers enrolled adults with early stage CLL who had not undergone chemotherapy or other treatment. All patients adhered to a Mediterranean-style diet.
After a washout period of 9-12 months, the researchers randomized 22 patients to extra virgin olive oil high in oleocanthal and oleacein (high OC/OL-EVOO). Patients in the intervention group consumed 40 mL/day of high OC/OL-EVOO before meals. Their average age was 71 years; 10 were women and 12 were men.
The primary outcomes included changes in hematological, biochemical, and apoptotic markers. After 6 months, patients in the intervention group showed a statistically significant reduction in white blood cells and lymphocyte count, compared with measurements taken 3 months before the intervention. The WBC decrease was greatest among patients with the highest WBC levels at baseline.
As for biochemical markers, the researchers observed a significant decrease in glucose levels during the intervention, but no significant effects on metabolic indexes or renal function.
After 3 months and also after 6 months of the olive oil intervention, patients showed a significant increase in the apoptotic markers ccK18 and Apo1-Fas (P ≤ .05 for both), as well as an increase in the cell cycle negative regulator p21. The dietary intervention also was associated with significant decreases in expression of the antiapoptotic protein survivin and in cyclin D, a positive cell cycle regulator protein.
Further, patients who had a high ccK18 level at baseline showed a significantly greater increase in ccK18 after the intervention, compared with those with lower ccK18 at baseline (P = .001).
Notably, “a negative correlation of the WBC at the end of the dietary intervention with the fluctuation of the protein expression of the apoptotic marker ccK18 (final – initial) was observed,” the researchers wrote in their discussion.
The study findings were limited by several factors including the small sample size, short intervention time, and pilot design, the researchers said. Other limitations include the possible effect of other unmeasured properties of olive oil.
However, the results reflect previous studies showing the benefits of a Mediterranean-type diet, and they represent the first clinical trial to indicate possible beneficial effects from oleocanthal and oleacein on the progression of CLL. Therefore, the authors concluded, the study is worthy of a large, multicenter trial.
Pilot data merit more research
In an interview, corresponding author Prokopios Magiatis, PhD, noted that CLL is “the most commonly diagnosed adult leukemia in Western countries and is responsible for about one in four cases of all leukemias.” CLL remains incurable in most patients, and ways to delay disease progression are needed.
“Oleocanthal is the active ingredient of early harvest olive oil with proven anticancer activities in vitro and in vivo,” Dr. Magiatis explained. “For this reason, it was a unique challenge to investigate the anticancer activity of this compound for the first time in humans through the dietary consumption of specifically selected olive oil.” He expressed surprise at the beneficial effects of high-oleocanthal olive oil, not only to the white blood cells, but also to glucose levels.
“It seems that oleocanthal can activate mechanisms related to the apoptosis of cancer cells, and also mechanisms related to blood glucose regulation without affecting any normal cells of the body,” he said. “All anticancer drugs usually have severe side effects, however the administration of 25 mg of oleocanthal through the dietary consumption of olive oil did not present any harmful effects for at least 6 months of everyday use.
“The addition of naturally produced high-oleocanthal olive oil in the diet of early-stage CLL patients at a dose of three tablespoons per day [40 mL] is a practice that may lower the cancerous white blood cells of the patients without any risk,” said Dr. Magiatis. “High-oleocanthal early-harvest olive oil has been consumed for centuries, and may be the key of longevity of several Mediterranean populations.
“In our study, the number of the white blood cells returned back to the number it was one year before the initiation of the study; this clearly shows that it could be a significant factor for the delay of the progress of the disease,” he said.
The current trial was a pilot study in one hospital with only 22 patients for 6 months, said Dr. Magiatis. “We are currently preparing the expansion of the study to other hospitals and other countries, and we aim to include at least 100 patients for at least 1 year, to validate the already-obtained beneficial results.”
The clinical trial is supported by the nonprofit organization World Olive Center for Health, he added.
The current study received no outside funding. The researchers had no financial conflicts to disclose.
Olive oil is a major component of the Mediterranean diet, and olive phenols have been shown to convey antioxidant, anti-inflammatory, anticancer, neuroprotective, and antidiabetic effects by modulating various molecular pathways, Andrea Paola Rojas Gil, PhD, of the University of Peloponnese, Tripoli, Greece, and colleagues wrote.
In most patients, CLL is incurable, but those at the early stages do not need immediate therapy and may benefit from an intervention to prevent disease progression, the authors wrote. Previous research suggested that dietary intervention exerts a salutary effect on early CLL, and in vitro studies suggested that oleocanthal, a component of extra virgin olive oil, induced anticancer activity.
In a study published in Frontiers in Oncology, the researchers enrolled adults with early stage CLL who had not undergone chemotherapy or other treatment. All patients adhered to a Mediterranean-style diet.
After a washout period of 9-12 months, the researchers randomized 22 patients to extra virgin olive oil high in oleocanthal and oleacein (high OC/OL-EVOO). Patients in the intervention group consumed 40 mL/day of high OC/OL-EVOO before meals. Their average age was 71 years; 10 were women and 12 were men.
The primary outcomes included changes in hematological, biochemical, and apoptotic markers. After 6 months, patients in the intervention group showed a statistically significant reduction in white blood cells and lymphocyte count, compared with measurements taken 3 months before the intervention. The WBC decrease was greatest among patients with the highest WBC levels at baseline.
As for biochemical markers, the researchers observed a significant decrease in glucose levels during the intervention, but no significant effects on metabolic indexes or renal function.
After 3 months and also after 6 months of the olive oil intervention, patients showed a significant increase in the apoptotic markers ccK18 and Apo1-Fas (P ≤ .05 for both), as well as an increase in the cell cycle negative regulator p21. The dietary intervention also was associated with significant decreases in expression of the antiapoptotic protein survivin and in cyclin D, a positive cell cycle regulator protein.
Further, patients who had a high ccK18 level at baseline showed a significantly greater increase in ccK18 after the intervention, compared with those with lower ccK18 at baseline (P = .001).
Notably, “a negative correlation of the WBC at the end of the dietary intervention with the fluctuation of the protein expression of the apoptotic marker ccK18 (final – initial) was observed,” the researchers wrote in their discussion.
The study findings were limited by several factors including the small sample size, short intervention time, and pilot design, the researchers said. Other limitations include the possible effect of other unmeasured properties of olive oil.
However, the results reflect previous studies showing the benefits of a Mediterranean-type diet, and they represent the first clinical trial to indicate possible beneficial effects from oleocanthal and oleacein on the progression of CLL. Therefore, the authors concluded, the study is worthy of a large, multicenter trial.
Pilot data merit more research
In an interview, corresponding author Prokopios Magiatis, PhD, noted that CLL is “the most commonly diagnosed adult leukemia in Western countries and is responsible for about one in four cases of all leukemias.” CLL remains incurable in most patients, and ways to delay disease progression are needed.
“Oleocanthal is the active ingredient of early harvest olive oil with proven anticancer activities in vitro and in vivo,” Dr. Magiatis explained. “For this reason, it was a unique challenge to investigate the anticancer activity of this compound for the first time in humans through the dietary consumption of specifically selected olive oil.” He expressed surprise at the beneficial effects of high-oleocanthal olive oil, not only to the white blood cells, but also to glucose levels.
“It seems that oleocanthal can activate mechanisms related to the apoptosis of cancer cells, and also mechanisms related to blood glucose regulation without affecting any normal cells of the body,” he said. “All anticancer drugs usually have severe side effects, however the administration of 25 mg of oleocanthal through the dietary consumption of olive oil did not present any harmful effects for at least 6 months of everyday use.
“The addition of naturally produced high-oleocanthal olive oil in the diet of early-stage CLL patients at a dose of three tablespoons per day [40 mL] is a practice that may lower the cancerous white blood cells of the patients without any risk,” said Dr. Magiatis. “High-oleocanthal early-harvest olive oil has been consumed for centuries, and may be the key of longevity of several Mediterranean populations.
“In our study, the number of the white blood cells returned back to the number it was one year before the initiation of the study; this clearly shows that it could be a significant factor for the delay of the progress of the disease,” he said.
The current trial was a pilot study in one hospital with only 22 patients for 6 months, said Dr. Magiatis. “We are currently preparing the expansion of the study to other hospitals and other countries, and we aim to include at least 100 patients for at least 1 year, to validate the already-obtained beneficial results.”
The clinical trial is supported by the nonprofit organization World Olive Center for Health, he added.
The current study received no outside funding. The researchers had no financial conflicts to disclose.
FROM FRONTIERS IN ONCOLOGY
Ways to lessen toxic effects of chemo in older adults
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Filling opioid prescriptions akin to a Sisyphean task
Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic,
A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.
She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.
Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.
I send an e-prescription for the same opioid Joan’s currently taking, but in a long-acting format that will slow-release over 8-10 hours, relieving her of the need to take a medication every 3-4 hours. I have learned over the years that nearly every long-acting opioid automatically generates a prior authorization request from the patient’s insurance company and so I immediately email our prior authorization team to submit to Joan’s insurance right away to avoid this extra delay.
Our prior authorization team is exceptionally responsive and submits these requests with urgency every time – they understand that cancer pain is a serious problem and we can’t wait 5 business days for answers. They are typically able to obtain an approved prior authorization for nearly every long-acting opioid I write within 24-48 hours.
But here’s where things go sideways.
First, the insurance company denies the prior authorization request, demanding that I revise the prescription from the long-acting version of the opioid she is currently taking to a cheaper, older opioid that she’s never tried before. In other words, they won’t cover the drug I requested without Joan first trying a completely different drug and failing it. This only makes sense for the insurance company’s bottom line – it makes no clinical sense at all. Why would I try a novel compound that Joan’s never had and one to which I have no idea how she’ll respond when I could keep her on the same compound knowing that she tolerates it just fine?
Past experience tells me insurance companies rarely budge on this, and appealing the decision would just introduce even more delay of care, so I begrudgingly change the prescription and send it again to the pharmacy. I message Joan to let her know that her insurance won’t cover my drug of choice and that we have to try this older one first.
A few hours later, Joan sends me a message: “My pharmacy says it’s going to take A WEEK to get the long-acting medicine!”
In the meantime, Joan has been using her short-acting opioid faster than anticipated because of her escalating pain – so she’s now running low on that as well.
I write for more of her short-acting opioid and e-script it to her pharmacy.
Within a few hours, we get another automatic response from her insurance that we’re going to need a prior authorization for additional short-acting opioid because she’s exceeded “quantity limitations,” which as far as I can tell is a completely arbitrary number not based on clinical evidence.
The prior auth team jumps on it and submits to override the quantity limit – successfully – and sends the override code to her pharmacy to reprocess the prescription.
But now the pharmacist tells Joan that they won’t fill the Rx anyway because it’s “too early.” They tell her that “state laws” prevent them from filling the scrip.
Is this true? I have no idea. I’m not an expert on California pharmacy law. All I know is that my patient is in pain and something needs to happen quickly.
I write for a second short-acting opioid – again a completely different compound. Ironically, this Rx goes through instantly without need for prior authorization. But now Joan has to switch to another new drug for no good medical reason.
If you’re still with me this far into the weeds, I’m grateful. In all it took a combined 4 hours of work (between myself and the prior auth team) to get two opioid Rx’s filled – and these were completely different medications than the ones I originally wrote for. I also had to move her prescriptions to the hospital’s pharmacy (another inconvenience for Joan and her family) so that she could get the medications in a timely manner. All this work to ensure that a single patient had adequate and timely pain relief and to prevent her from having to make an unnecessary visit to the emergency department for pain crisis.
This is just a regular day in outpatient palliative care in the era of the opioid epidemic.
The epidemic has caused tremendous pain and suffering for millions of people over the past 2 decades – namely those lost to opioid overdoses and their loved ones. And for the most part, tightening access to opioids for routine aches and pains among a relatively healthy population is not wrong, in my opinion, as long as those restrictions are based in good faith on robust evidence.
But the hidden cost of the Centers for Disease Control and Prevention’s 2016 opioid prescribing guidelines for nonmalignant pain, as well as the flurry of restrictive state laws they generated, is felt every day by patients with serious illness even though the guidelines were never meant to affect them. Patients with active cancer, receiving palliative care services, or at the end of life, were supposed to be exempted from these guidelines since good evidence supports the use of opioids in these populations.
Instead of preserving access to desperately needed pain medicine for those suffering with serious illness, states and insurers have aggressively sought to gatekeep opioids from everyone, resulting in stigma, delays, and needless suffering.
Several recent studies have revealed the effects of this gatekeeping on patients with cancer.
A qualitative study with 26 advanced cancer patients described the demoralization and stigma many patients felt when taking opioids, which they directly tied to media messaging around the opioid epidemic. Even when they reluctantly agreed to take opioids to treat cancer-related pain, there were systemic impediments to achieving adequate pain relief – similar to my experience with Joan – that were directly caused by insurance and pharmacy constraints.
Those of us who care for oncology patients also appear to be undertreating cancer-related pain. Another recent study that found the amount of opioid medications prescribed to an advanced cancer patient near the end of life dropped by 38% between 2007 and 2017. The authors suggest that a direct consequence of this decline in appropriate opioid prescribing is an observed 50% rise in emergency department visits over the same time period by cancer patients for pain-related reasons.
This makes sense – if patients aren’t routinely prescribed the opioids they need to manage their cancer-related pain; or, if the stigma against using opioids is so harsh that it causes patients to shun opioids; or, if there are so many system barriers in place to prevent patients from obtaining opioids in a timely manner – then patients’ pain will crescendo, leaving them with little alternative but to head to the emergency department.
This undertreatment is corroborated by another study that examined data from the Centers for Medicare & Medicaid Services Part D prescriber database between 2013 and 2017, finding that both oncologists and nononcologists prescribed about 21% fewer opioids to Medicare beneficiaries during that time, compared with the period prior to 2013.
Interestingly, the researchers also found that opioid prescribing by palliative care providers increased by 15% over the same period. On a positive note, this suggests the presence of a growing outpatient palliative care workforce. But it may also reflect growing unease among oncologists with the perceived liability for prescribing opioids and a desire to ask other specialists to take on this liability. At the same time, it may reflect the very real and ever-increasing administrative burden associated with prescribing opioids and the fact that busy oncologists may not have time to spend on this aspect of cancer care. Thus, as palliative care clinicians become more visible and numerous in the outpatient arena, oncologists may increasingly ask palliative care clinicians like myself to take this on.
The problem with this is that merely handing off the administrative burden to another clinician doesn’t address the underlying problem. Anecdotal evidence suggests (and my own experiences corroborate) this administrative burden can cause real harm. A survey of 1,000 physicians conducted by the American Medical Association in 2021 found that 93% of respondents reported a delay in patient care due to prior authorization burden and 34% of respondents reported that their patients had suffered a “serious adverse event” due to prior authorization requirements.
The CDC recently announced it will take steps to revise the 2016 opioid prescribing guidelines for chronic pain after hearing from members of the medical community as well as patients living with chronic pain about the harsh, unintended consequences of the guidelines. I can only hope that insurance companies will follow suit, revising their opioid prior authorization requirements to finally come into alignment with the rational, safe use of opioids in patients with advanced cancer. It’s too bad that any improvement in the future will be too late for the millions of patients who have suffered irreversible iatrogenic harms due to delays in achieving adequate pain relief.
Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.
Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic,
A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.
She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.
Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.
I send an e-prescription for the same opioid Joan’s currently taking, but in a long-acting format that will slow-release over 8-10 hours, relieving her of the need to take a medication every 3-4 hours. I have learned over the years that nearly every long-acting opioid automatically generates a prior authorization request from the patient’s insurance company and so I immediately email our prior authorization team to submit to Joan’s insurance right away to avoid this extra delay.
Our prior authorization team is exceptionally responsive and submits these requests with urgency every time – they understand that cancer pain is a serious problem and we can’t wait 5 business days for answers. They are typically able to obtain an approved prior authorization for nearly every long-acting opioid I write within 24-48 hours.
But here’s where things go sideways.
First, the insurance company denies the prior authorization request, demanding that I revise the prescription from the long-acting version of the opioid she is currently taking to a cheaper, older opioid that she’s never tried before. In other words, they won’t cover the drug I requested without Joan first trying a completely different drug and failing it. This only makes sense for the insurance company’s bottom line – it makes no clinical sense at all. Why would I try a novel compound that Joan’s never had and one to which I have no idea how she’ll respond when I could keep her on the same compound knowing that she tolerates it just fine?
Past experience tells me insurance companies rarely budge on this, and appealing the decision would just introduce even more delay of care, so I begrudgingly change the prescription and send it again to the pharmacy. I message Joan to let her know that her insurance won’t cover my drug of choice and that we have to try this older one first.
A few hours later, Joan sends me a message: “My pharmacy says it’s going to take A WEEK to get the long-acting medicine!”
In the meantime, Joan has been using her short-acting opioid faster than anticipated because of her escalating pain – so she’s now running low on that as well.
I write for more of her short-acting opioid and e-script it to her pharmacy.
Within a few hours, we get another automatic response from her insurance that we’re going to need a prior authorization for additional short-acting opioid because she’s exceeded “quantity limitations,” which as far as I can tell is a completely arbitrary number not based on clinical evidence.
The prior auth team jumps on it and submits to override the quantity limit – successfully – and sends the override code to her pharmacy to reprocess the prescription.
But now the pharmacist tells Joan that they won’t fill the Rx anyway because it’s “too early.” They tell her that “state laws” prevent them from filling the scrip.
Is this true? I have no idea. I’m not an expert on California pharmacy law. All I know is that my patient is in pain and something needs to happen quickly.
I write for a second short-acting opioid – again a completely different compound. Ironically, this Rx goes through instantly without need for prior authorization. But now Joan has to switch to another new drug for no good medical reason.
If you’re still with me this far into the weeds, I’m grateful. In all it took a combined 4 hours of work (between myself and the prior auth team) to get two opioid Rx’s filled – and these were completely different medications than the ones I originally wrote for. I also had to move her prescriptions to the hospital’s pharmacy (another inconvenience for Joan and her family) so that she could get the medications in a timely manner. All this work to ensure that a single patient had adequate and timely pain relief and to prevent her from having to make an unnecessary visit to the emergency department for pain crisis.
This is just a regular day in outpatient palliative care in the era of the opioid epidemic.
The epidemic has caused tremendous pain and suffering for millions of people over the past 2 decades – namely those lost to opioid overdoses and their loved ones. And for the most part, tightening access to opioids for routine aches and pains among a relatively healthy population is not wrong, in my opinion, as long as those restrictions are based in good faith on robust evidence.
But the hidden cost of the Centers for Disease Control and Prevention’s 2016 opioid prescribing guidelines for nonmalignant pain, as well as the flurry of restrictive state laws they generated, is felt every day by patients with serious illness even though the guidelines were never meant to affect them. Patients with active cancer, receiving palliative care services, or at the end of life, were supposed to be exempted from these guidelines since good evidence supports the use of opioids in these populations.
Instead of preserving access to desperately needed pain medicine for those suffering with serious illness, states and insurers have aggressively sought to gatekeep opioids from everyone, resulting in stigma, delays, and needless suffering.
Several recent studies have revealed the effects of this gatekeeping on patients with cancer.
A qualitative study with 26 advanced cancer patients described the demoralization and stigma many patients felt when taking opioids, which they directly tied to media messaging around the opioid epidemic. Even when they reluctantly agreed to take opioids to treat cancer-related pain, there were systemic impediments to achieving adequate pain relief – similar to my experience with Joan – that were directly caused by insurance and pharmacy constraints.
Those of us who care for oncology patients also appear to be undertreating cancer-related pain. Another recent study that found the amount of opioid medications prescribed to an advanced cancer patient near the end of life dropped by 38% between 2007 and 2017. The authors suggest that a direct consequence of this decline in appropriate opioid prescribing is an observed 50% rise in emergency department visits over the same time period by cancer patients for pain-related reasons.
This makes sense – if patients aren’t routinely prescribed the opioids they need to manage their cancer-related pain; or, if the stigma against using opioids is so harsh that it causes patients to shun opioids; or, if there are so many system barriers in place to prevent patients from obtaining opioids in a timely manner – then patients’ pain will crescendo, leaving them with little alternative but to head to the emergency department.
This undertreatment is corroborated by another study that examined data from the Centers for Medicare & Medicaid Services Part D prescriber database between 2013 and 2017, finding that both oncologists and nononcologists prescribed about 21% fewer opioids to Medicare beneficiaries during that time, compared with the period prior to 2013.
Interestingly, the researchers also found that opioid prescribing by palliative care providers increased by 15% over the same period. On a positive note, this suggests the presence of a growing outpatient palliative care workforce. But it may also reflect growing unease among oncologists with the perceived liability for prescribing opioids and a desire to ask other specialists to take on this liability. At the same time, it may reflect the very real and ever-increasing administrative burden associated with prescribing opioids and the fact that busy oncologists may not have time to spend on this aspect of cancer care. Thus, as palliative care clinicians become more visible and numerous in the outpatient arena, oncologists may increasingly ask palliative care clinicians like myself to take this on.
The problem with this is that merely handing off the administrative burden to another clinician doesn’t address the underlying problem. Anecdotal evidence suggests (and my own experiences corroborate) this administrative burden can cause real harm. A survey of 1,000 physicians conducted by the American Medical Association in 2021 found that 93% of respondents reported a delay in patient care due to prior authorization burden and 34% of respondents reported that their patients had suffered a “serious adverse event” due to prior authorization requirements.
The CDC recently announced it will take steps to revise the 2016 opioid prescribing guidelines for chronic pain after hearing from members of the medical community as well as patients living with chronic pain about the harsh, unintended consequences of the guidelines. I can only hope that insurance companies will follow suit, revising their opioid prior authorization requirements to finally come into alignment with the rational, safe use of opioids in patients with advanced cancer. It’s too bad that any improvement in the future will be too late for the millions of patients who have suffered irreversible iatrogenic harms due to delays in achieving adequate pain relief.
Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.
Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic,
A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.
She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.
Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.
I send an e-prescription for the same opioid Joan’s currently taking, but in a long-acting format that will slow-release over 8-10 hours, relieving her of the need to take a medication every 3-4 hours. I have learned over the years that nearly every long-acting opioid automatically generates a prior authorization request from the patient’s insurance company and so I immediately email our prior authorization team to submit to Joan’s insurance right away to avoid this extra delay.
Our prior authorization team is exceptionally responsive and submits these requests with urgency every time – they understand that cancer pain is a serious problem and we can’t wait 5 business days for answers. They are typically able to obtain an approved prior authorization for nearly every long-acting opioid I write within 24-48 hours.
But here’s where things go sideways.
First, the insurance company denies the prior authorization request, demanding that I revise the prescription from the long-acting version of the opioid she is currently taking to a cheaper, older opioid that she’s never tried before. In other words, they won’t cover the drug I requested without Joan first trying a completely different drug and failing it. This only makes sense for the insurance company’s bottom line – it makes no clinical sense at all. Why would I try a novel compound that Joan’s never had and one to which I have no idea how she’ll respond when I could keep her on the same compound knowing that she tolerates it just fine?
Past experience tells me insurance companies rarely budge on this, and appealing the decision would just introduce even more delay of care, so I begrudgingly change the prescription and send it again to the pharmacy. I message Joan to let her know that her insurance won’t cover my drug of choice and that we have to try this older one first.
A few hours later, Joan sends me a message: “My pharmacy says it’s going to take A WEEK to get the long-acting medicine!”
In the meantime, Joan has been using her short-acting opioid faster than anticipated because of her escalating pain – so she’s now running low on that as well.
I write for more of her short-acting opioid and e-script it to her pharmacy.
Within a few hours, we get another automatic response from her insurance that we’re going to need a prior authorization for additional short-acting opioid because she’s exceeded “quantity limitations,” which as far as I can tell is a completely arbitrary number not based on clinical evidence.
The prior auth team jumps on it and submits to override the quantity limit – successfully – and sends the override code to her pharmacy to reprocess the prescription.
But now the pharmacist tells Joan that they won’t fill the Rx anyway because it’s “too early.” They tell her that “state laws” prevent them from filling the scrip.
Is this true? I have no idea. I’m not an expert on California pharmacy law. All I know is that my patient is in pain and something needs to happen quickly.
I write for a second short-acting opioid – again a completely different compound. Ironically, this Rx goes through instantly without need for prior authorization. But now Joan has to switch to another new drug for no good medical reason.
If you’re still with me this far into the weeds, I’m grateful. In all it took a combined 4 hours of work (between myself and the prior auth team) to get two opioid Rx’s filled – and these were completely different medications than the ones I originally wrote for. I also had to move her prescriptions to the hospital’s pharmacy (another inconvenience for Joan and her family) so that she could get the medications in a timely manner. All this work to ensure that a single patient had adequate and timely pain relief and to prevent her from having to make an unnecessary visit to the emergency department for pain crisis.
This is just a regular day in outpatient palliative care in the era of the opioid epidemic.
The epidemic has caused tremendous pain and suffering for millions of people over the past 2 decades – namely those lost to opioid overdoses and their loved ones. And for the most part, tightening access to opioids for routine aches and pains among a relatively healthy population is not wrong, in my opinion, as long as those restrictions are based in good faith on robust evidence.
But the hidden cost of the Centers for Disease Control and Prevention’s 2016 opioid prescribing guidelines for nonmalignant pain, as well as the flurry of restrictive state laws they generated, is felt every day by patients with serious illness even though the guidelines were never meant to affect them. Patients with active cancer, receiving palliative care services, or at the end of life, were supposed to be exempted from these guidelines since good evidence supports the use of opioids in these populations.
Instead of preserving access to desperately needed pain medicine for those suffering with serious illness, states and insurers have aggressively sought to gatekeep opioids from everyone, resulting in stigma, delays, and needless suffering.
Several recent studies have revealed the effects of this gatekeeping on patients with cancer.
A qualitative study with 26 advanced cancer patients described the demoralization and stigma many patients felt when taking opioids, which they directly tied to media messaging around the opioid epidemic. Even when they reluctantly agreed to take opioids to treat cancer-related pain, there were systemic impediments to achieving adequate pain relief – similar to my experience with Joan – that were directly caused by insurance and pharmacy constraints.
Those of us who care for oncology patients also appear to be undertreating cancer-related pain. Another recent study that found the amount of opioid medications prescribed to an advanced cancer patient near the end of life dropped by 38% between 2007 and 2017. The authors suggest that a direct consequence of this decline in appropriate opioid prescribing is an observed 50% rise in emergency department visits over the same time period by cancer patients for pain-related reasons.
This makes sense – if patients aren’t routinely prescribed the opioids they need to manage their cancer-related pain; or, if the stigma against using opioids is so harsh that it causes patients to shun opioids; or, if there are so many system barriers in place to prevent patients from obtaining opioids in a timely manner – then patients’ pain will crescendo, leaving them with little alternative but to head to the emergency department.
This undertreatment is corroborated by another study that examined data from the Centers for Medicare & Medicaid Services Part D prescriber database between 2013 and 2017, finding that both oncologists and nononcologists prescribed about 21% fewer opioids to Medicare beneficiaries during that time, compared with the period prior to 2013.
Interestingly, the researchers also found that opioid prescribing by palliative care providers increased by 15% over the same period. On a positive note, this suggests the presence of a growing outpatient palliative care workforce. But it may also reflect growing unease among oncologists with the perceived liability for prescribing opioids and a desire to ask other specialists to take on this liability. At the same time, it may reflect the very real and ever-increasing administrative burden associated with prescribing opioids and the fact that busy oncologists may not have time to spend on this aspect of cancer care. Thus, as palliative care clinicians become more visible and numerous in the outpatient arena, oncologists may increasingly ask palliative care clinicians like myself to take this on.
The problem with this is that merely handing off the administrative burden to another clinician doesn’t address the underlying problem. Anecdotal evidence suggests (and my own experiences corroborate) this administrative burden can cause real harm. A survey of 1,000 physicians conducted by the American Medical Association in 2021 found that 93% of respondents reported a delay in patient care due to prior authorization burden and 34% of respondents reported that their patients had suffered a “serious adverse event” due to prior authorization requirements.
The CDC recently announced it will take steps to revise the 2016 opioid prescribing guidelines for chronic pain after hearing from members of the medical community as well as patients living with chronic pain about the harsh, unintended consequences of the guidelines. I can only hope that insurance companies will follow suit, revising their opioid prior authorization requirements to finally come into alignment with the rational, safe use of opioids in patients with advanced cancer. It’s too bad that any improvement in the future will be too late for the millions of patients who have suffered irreversible iatrogenic harms due to delays in achieving adequate pain relief.
Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.
Global data suggest rising CLL incidence since 1990
Either way, “to our best knowledge, this study is the first study to provide a comprehensive description of the epidemiology and global burden of CLL worldwide,” the authors reported in BioMedical Engineering Online.
The findings are an evaluation of data from the 2019 Global Burden of Disease study, which includes epidemiological data on 369 diseases in 204 nations and territories around the world.
According to the analysis, the age-standardized incidence rate of CLL rose globally over the last 3 decades, from 0.76 per 100,000 persons in 1990 to 1.34 per 100,000 in 2019, for an estimated annual percentage change of 1.86%.
While increases were observed across all economic levels, the highest increases were observed in regions with the highest social determinant index. Notably, the fastest rise was observed in middle-income regions.
“What cannot be ignored is the rapid growth of the disease burden in middle [social determinant index] regions, which potentially indicated an underestimated incidence and mortality in underdeveloped countries,” write the authors, led by senior author Huafeng Wang, MD, of the department of hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
The highest annual age-standardized incidence rates in 2019 occurred in western Europe, high-income areas of North America and central Europe, while the fastest increase in the incidence of CLL occurred in east Asia, central Europe, and Andean Latin America, according to the study.
Mortality rates
The age-standardized death rate from CLL also increased globally, from 0.40 per 100,000 persons in 1990 to 0.58 per 100,000 in 2019, for an estimated annual percentage change of 1.17.
The increases in death rates were observed across all income regions over the study period, with the highest age-standardized death rate in 2019, consistent with incidence rates, occurring in the highest-income regions, specifically in central Europe, western Europe, and high-income North America.
The geographic trends were similar in terms of disability-adjusted life-years, which increased globally from 9.20 per 100,000 persons in 1990 to 12.26 per 100,000 in 2019, for an estimated annual percentage change of 0.92%.
The authors noted that the geographic variation of CLL is consistent with research suggesting that White ancestry is a risk factor for this leukemia. And while the incidence of CLL is generally low in the 22 nations of the Arab League, the burden of disease is high in Israel.
Age and gender
The study shows that, during the past 30 years in general, CLL was more common among males, with some regional differences. For instance, in contrast to global trends, females in low-income regions accounted for the majority of incidence and mortality.
The majority of CLL cases occurred in people over the age of 50, which is consistent with known patterns of CLL occurring in older patients. Of note, the majority of cases between the ages of 50 and 69 were in low-income regions, while more than half of the incidence cases in higher-income regions were among those over the age of 70.
Risk factors
Key risk factors that may to be linked to CLL-related mortality and disability include high body mass index, occupational exposure to benzene and formaldehyde, and smoking, which was the strongest risk factor, the authors reported.
Obesity has previously been linked with an increased risk of lymphohematopoietic cancers in general and with poorer responses to treatment and reduced progression-free survival in CLL, in particular.
While the database otherwise provided only limited insights into potential CLL risk factors, “among the factors [the database] provided, the risk of benzene and formaldehyde exposure should be paid attention to,” Dr. Wang said in an interview.
“Different from other risk factors, emerging evidence has clearly pointed out the close relationship between benzene and formaldehyde exposure and hematological malignancies,” he explained. “With globalization, a large number of factories moved to less developed regions. The problem of occupational toxic exposure needs to be addressed.”
In general, the trends in the current study are consistent with previous research showing that, while there was a significant global decrease in leukemia incidence between 1990 and 2017, the incidence rates of CLL as well as acute myeloid leukemia (AML) significantly increased in most countries during that period.
“The age-standardized incidence rate of AML has steadily increased over the past 30 years, but not as rapidly as CLL,” Dr. Wang said.
He added that an encouraging sign is the “significant decline” in the age-standardized rate of chronic myeloid leukemia seen with the advent of tyrosine kinase inhibitors (TKIs).
“Perhaps for CLL, the emergence of epoch-making therapies like TKIs will also contribute to the reduction of disease burden [with that disease],” he said.
Surveillance bias?
The authors note a key caveat that the lower rates observed in low-income regions could be related to underreporting and lower screening of cancers in those regions. However, commenting on the study, Robert Peter Gale, MD, PhD, suggested that, conversely, the trends may represent a surveillance bias, reflecting an increased detection of CLL.
In fact, “it is most unlikely the incidence of CLL is really increasing,” Dr. Gale, visiting professor of hematology at the Hematology Research Centre, department of immunology and inflammation, Imperial College London, said in an interview.
“More than one-half of people with CLL have no signs or symptoms, and the diagnosis is made when they have a blood test done for unrelated reasons,” such as in the process of qualifying for life or medical insurance or for a new job, he explained. “The more testing you do, the more cases you will detect.”
Dr. Gale pointed out that research his team has conducted in China also showed an increasing incidence of CLL. However, “on closer study, we found about two-thirds of cases were incidental, namely cases detected under circumstances [such as blood testing for a job].”
Shen-Miao Yang, MD, first author of that study, agreed and noted that improved treatment with drugs such as Bruton kinase inhibitors also can have the effect of increasing incidence – by extending lives.
“More patients are diagnosed, [and] receive the new agent, and their longer survival contributes to the increased burden of CLL,” Dr. Yang of People’s Hospital of Peking University, Peking University Institute of Hematology, Beijing, said in an interview.
Furthermore, “advanced techniques such as flow cytometry and fluorescence in situ hybridization are routinely used for the diagnosis and prognosis of CLL patients – that also increases the CLL burden.”
Dr. Yang had no disclosures to report. Dr. Gale disclosed that he is a consultant to BeiGene, Fusion Pharma, La Jolla NanoMedical, MingSight Pharmaceuticals, CStone Pharmaceuticals, NexImmune, and Prolacta Bioscience; an adviser to Antengene Biotech; medical director of FFF Enterprises; a partner of AZCA; member of the board of directors of the Russian Foundation for Cancer Research Support; and on the scientific advisory board of StemRad.
Either way, “to our best knowledge, this study is the first study to provide a comprehensive description of the epidemiology and global burden of CLL worldwide,” the authors reported in BioMedical Engineering Online.
The findings are an evaluation of data from the 2019 Global Burden of Disease study, which includes epidemiological data on 369 diseases in 204 nations and territories around the world.
According to the analysis, the age-standardized incidence rate of CLL rose globally over the last 3 decades, from 0.76 per 100,000 persons in 1990 to 1.34 per 100,000 in 2019, for an estimated annual percentage change of 1.86%.
While increases were observed across all economic levels, the highest increases were observed in regions with the highest social determinant index. Notably, the fastest rise was observed in middle-income regions.
“What cannot be ignored is the rapid growth of the disease burden in middle [social determinant index] regions, which potentially indicated an underestimated incidence and mortality in underdeveloped countries,” write the authors, led by senior author Huafeng Wang, MD, of the department of hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
The highest annual age-standardized incidence rates in 2019 occurred in western Europe, high-income areas of North America and central Europe, while the fastest increase in the incidence of CLL occurred in east Asia, central Europe, and Andean Latin America, according to the study.
Mortality rates
The age-standardized death rate from CLL also increased globally, from 0.40 per 100,000 persons in 1990 to 0.58 per 100,000 in 2019, for an estimated annual percentage change of 1.17.
The increases in death rates were observed across all income regions over the study period, with the highest age-standardized death rate in 2019, consistent with incidence rates, occurring in the highest-income regions, specifically in central Europe, western Europe, and high-income North America.
The geographic trends were similar in terms of disability-adjusted life-years, which increased globally from 9.20 per 100,000 persons in 1990 to 12.26 per 100,000 in 2019, for an estimated annual percentage change of 0.92%.
The authors noted that the geographic variation of CLL is consistent with research suggesting that White ancestry is a risk factor for this leukemia. And while the incidence of CLL is generally low in the 22 nations of the Arab League, the burden of disease is high in Israel.
Age and gender
The study shows that, during the past 30 years in general, CLL was more common among males, with some regional differences. For instance, in contrast to global trends, females in low-income regions accounted for the majority of incidence and mortality.
The majority of CLL cases occurred in people over the age of 50, which is consistent with known patterns of CLL occurring in older patients. Of note, the majority of cases between the ages of 50 and 69 were in low-income regions, while more than half of the incidence cases in higher-income regions were among those over the age of 70.
Risk factors
Key risk factors that may to be linked to CLL-related mortality and disability include high body mass index, occupational exposure to benzene and formaldehyde, and smoking, which was the strongest risk factor, the authors reported.
Obesity has previously been linked with an increased risk of lymphohematopoietic cancers in general and with poorer responses to treatment and reduced progression-free survival in CLL, in particular.
While the database otherwise provided only limited insights into potential CLL risk factors, “among the factors [the database] provided, the risk of benzene and formaldehyde exposure should be paid attention to,” Dr. Wang said in an interview.
“Different from other risk factors, emerging evidence has clearly pointed out the close relationship between benzene and formaldehyde exposure and hematological malignancies,” he explained. “With globalization, a large number of factories moved to less developed regions. The problem of occupational toxic exposure needs to be addressed.”
In general, the trends in the current study are consistent with previous research showing that, while there was a significant global decrease in leukemia incidence between 1990 and 2017, the incidence rates of CLL as well as acute myeloid leukemia (AML) significantly increased in most countries during that period.
“The age-standardized incidence rate of AML has steadily increased over the past 30 years, but not as rapidly as CLL,” Dr. Wang said.
He added that an encouraging sign is the “significant decline” in the age-standardized rate of chronic myeloid leukemia seen with the advent of tyrosine kinase inhibitors (TKIs).
“Perhaps for CLL, the emergence of epoch-making therapies like TKIs will also contribute to the reduction of disease burden [with that disease],” he said.
Surveillance bias?
The authors note a key caveat that the lower rates observed in low-income regions could be related to underreporting and lower screening of cancers in those regions. However, commenting on the study, Robert Peter Gale, MD, PhD, suggested that, conversely, the trends may represent a surveillance bias, reflecting an increased detection of CLL.
In fact, “it is most unlikely the incidence of CLL is really increasing,” Dr. Gale, visiting professor of hematology at the Hematology Research Centre, department of immunology and inflammation, Imperial College London, said in an interview.
“More than one-half of people with CLL have no signs or symptoms, and the diagnosis is made when they have a blood test done for unrelated reasons,” such as in the process of qualifying for life or medical insurance or for a new job, he explained. “The more testing you do, the more cases you will detect.”
Dr. Gale pointed out that research his team has conducted in China also showed an increasing incidence of CLL. However, “on closer study, we found about two-thirds of cases were incidental, namely cases detected under circumstances [such as blood testing for a job].”
Shen-Miao Yang, MD, first author of that study, agreed and noted that improved treatment with drugs such as Bruton kinase inhibitors also can have the effect of increasing incidence – by extending lives.
“More patients are diagnosed, [and] receive the new agent, and their longer survival contributes to the increased burden of CLL,” Dr. Yang of People’s Hospital of Peking University, Peking University Institute of Hematology, Beijing, said in an interview.
Furthermore, “advanced techniques such as flow cytometry and fluorescence in situ hybridization are routinely used for the diagnosis and prognosis of CLL patients – that also increases the CLL burden.”
Dr. Yang had no disclosures to report. Dr. Gale disclosed that he is a consultant to BeiGene, Fusion Pharma, La Jolla NanoMedical, MingSight Pharmaceuticals, CStone Pharmaceuticals, NexImmune, and Prolacta Bioscience; an adviser to Antengene Biotech; medical director of FFF Enterprises; a partner of AZCA; member of the board of directors of the Russian Foundation for Cancer Research Support; and on the scientific advisory board of StemRad.
Either way, “to our best knowledge, this study is the first study to provide a comprehensive description of the epidemiology and global burden of CLL worldwide,” the authors reported in BioMedical Engineering Online.
The findings are an evaluation of data from the 2019 Global Burden of Disease study, which includes epidemiological data on 369 diseases in 204 nations and territories around the world.
According to the analysis, the age-standardized incidence rate of CLL rose globally over the last 3 decades, from 0.76 per 100,000 persons in 1990 to 1.34 per 100,000 in 2019, for an estimated annual percentage change of 1.86%.
While increases were observed across all economic levels, the highest increases were observed in regions with the highest social determinant index. Notably, the fastest rise was observed in middle-income regions.
“What cannot be ignored is the rapid growth of the disease burden in middle [social determinant index] regions, which potentially indicated an underestimated incidence and mortality in underdeveloped countries,” write the authors, led by senior author Huafeng Wang, MD, of the department of hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
The highest annual age-standardized incidence rates in 2019 occurred in western Europe, high-income areas of North America and central Europe, while the fastest increase in the incidence of CLL occurred in east Asia, central Europe, and Andean Latin America, according to the study.
Mortality rates
The age-standardized death rate from CLL also increased globally, from 0.40 per 100,000 persons in 1990 to 0.58 per 100,000 in 2019, for an estimated annual percentage change of 1.17.
The increases in death rates were observed across all income regions over the study period, with the highest age-standardized death rate in 2019, consistent with incidence rates, occurring in the highest-income regions, specifically in central Europe, western Europe, and high-income North America.
The geographic trends were similar in terms of disability-adjusted life-years, which increased globally from 9.20 per 100,000 persons in 1990 to 12.26 per 100,000 in 2019, for an estimated annual percentage change of 0.92%.
The authors noted that the geographic variation of CLL is consistent with research suggesting that White ancestry is a risk factor for this leukemia. And while the incidence of CLL is generally low in the 22 nations of the Arab League, the burden of disease is high in Israel.
Age and gender
The study shows that, during the past 30 years in general, CLL was more common among males, with some regional differences. For instance, in contrast to global trends, females in low-income regions accounted for the majority of incidence and mortality.
The majority of CLL cases occurred in people over the age of 50, which is consistent with known patterns of CLL occurring in older patients. Of note, the majority of cases between the ages of 50 and 69 were in low-income regions, while more than half of the incidence cases in higher-income regions were among those over the age of 70.
Risk factors
Key risk factors that may to be linked to CLL-related mortality and disability include high body mass index, occupational exposure to benzene and formaldehyde, and smoking, which was the strongest risk factor, the authors reported.
Obesity has previously been linked with an increased risk of lymphohematopoietic cancers in general and with poorer responses to treatment and reduced progression-free survival in CLL, in particular.
While the database otherwise provided only limited insights into potential CLL risk factors, “among the factors [the database] provided, the risk of benzene and formaldehyde exposure should be paid attention to,” Dr. Wang said in an interview.
“Different from other risk factors, emerging evidence has clearly pointed out the close relationship between benzene and formaldehyde exposure and hematological malignancies,” he explained. “With globalization, a large number of factories moved to less developed regions. The problem of occupational toxic exposure needs to be addressed.”
In general, the trends in the current study are consistent with previous research showing that, while there was a significant global decrease in leukemia incidence between 1990 and 2017, the incidence rates of CLL as well as acute myeloid leukemia (AML) significantly increased in most countries during that period.
“The age-standardized incidence rate of AML has steadily increased over the past 30 years, but not as rapidly as CLL,” Dr. Wang said.
He added that an encouraging sign is the “significant decline” in the age-standardized rate of chronic myeloid leukemia seen with the advent of tyrosine kinase inhibitors (TKIs).
“Perhaps for CLL, the emergence of epoch-making therapies like TKIs will also contribute to the reduction of disease burden [with that disease],” he said.
Surveillance bias?
The authors note a key caveat that the lower rates observed in low-income regions could be related to underreporting and lower screening of cancers in those regions. However, commenting on the study, Robert Peter Gale, MD, PhD, suggested that, conversely, the trends may represent a surveillance bias, reflecting an increased detection of CLL.
In fact, “it is most unlikely the incidence of CLL is really increasing,” Dr. Gale, visiting professor of hematology at the Hematology Research Centre, department of immunology and inflammation, Imperial College London, said in an interview.
“More than one-half of people with CLL have no signs or symptoms, and the diagnosis is made when they have a blood test done for unrelated reasons,” such as in the process of qualifying for life or medical insurance or for a new job, he explained. “The more testing you do, the more cases you will detect.”
Dr. Gale pointed out that research his team has conducted in China also showed an increasing incidence of CLL. However, “on closer study, we found about two-thirds of cases were incidental, namely cases detected under circumstances [such as blood testing for a job].”
Shen-Miao Yang, MD, first author of that study, agreed and noted that improved treatment with drugs such as Bruton kinase inhibitors also can have the effect of increasing incidence – by extending lives.
“More patients are diagnosed, [and] receive the new agent, and their longer survival contributes to the increased burden of CLL,” Dr. Yang of People’s Hospital of Peking University, Peking University Institute of Hematology, Beijing, said in an interview.
Furthermore, “advanced techniques such as flow cytometry and fluorescence in situ hybridization are routinely used for the diagnosis and prognosis of CLL patients – that also increases the CLL burden.”
Dr. Yang had no disclosures to report. Dr. Gale disclosed that he is a consultant to BeiGene, Fusion Pharma, La Jolla NanoMedical, MingSight Pharmaceuticals, CStone Pharmaceuticals, NexImmune, and Prolacta Bioscience; an adviser to Antengene Biotech; medical director of FFF Enterprises; a partner of AZCA; member of the board of directors of the Russian Foundation for Cancer Research Support; and on the scientific advisory board of StemRad.
FROM BIOMEDICAL ENGINEERING ONLINE
Women at higher risk of serious adverse events from cancer therapy
and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.
The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.
The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.
Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.
The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.
The article was published online on Feb. 4 in the Journal of Clinical Oncology.
“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.
A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.
Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.
Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
Study details
The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.
Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.
Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.
After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.
Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.
As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.
The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.
However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.
The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.
A version of this article first appeared on Medscape.com.
and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.
The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.
The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.
Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.
The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.
The article was published online on Feb. 4 in the Journal of Clinical Oncology.
“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.
A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.
Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.
Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
Study details
The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.
Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.
Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.
After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.
Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.
As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.
The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.
However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.
The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.
A version of this article first appeared on Medscape.com.
and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.
The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.
The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.
Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.
The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.
The article was published online on Feb. 4 in the Journal of Clinical Oncology.
“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.
A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.
Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.
Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
Study details
The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.
Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.
Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.
After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.
Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.
As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.
The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.
However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.
The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.
A version of this article first appeared on Medscape.com.
“I didn’t want to meet you.” Dispelling myths about palliative care
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.