AVAHO

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.

“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said

Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”

Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.  

The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”

Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.

The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”

Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”

Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”

Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”

Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.

Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”

“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.

Hartzfeld reports no disclosures.

The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.

“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said

Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”

Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.  

The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”

Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.

The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”

Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”

Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”

Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”

Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.

Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”

“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.

Hartzfeld reports no disclosures.

The U.S. Department of Veteran Affairs (VA) has been unable to provide genetic counseling to veterans at the same level as the civilian community, and other gaps exist, a genetic counselor told oncologist and hematologist colleagues. The good news is that telemedicine is turning out to be a valuable and proven way to reach veterans who need this kind of care, she said, although certain patients are being left behind.

“To me, telehealth is no doubt the way to go. But it is really important that we continue to look into these disparities, what's causing them, and how we can find a path forward,” said

Deborah Hartzfeld, MS, CGC, of the Genomic Medicine Service based in Salt Lake City, Utah. She spoke in a presentation at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) that was held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

As Harzfeld explained, the genetic counselor workforce is expanding along with the number of indications for genetic testing, especially in cancer, “where the need for germline genetic testing for inherited cancer genes becomes broader every year.”

Genetic counselors are a homogenous group, she said, as revealed by a 2021 survey of most of the nation’s 5,629 certified generic counselors. The North American survey, by the National Society of Genetic Counselors, found that 94% of respondents identified themselves as female, and 90% were white/non-Hispanic.  

The survey report also noted that “the genetic counseling profession has grown by over 100% in the last 10 years and is expected to grow another 100% over the next 10 years. By 2025 there should be nearly 7,500 certified genetic counselors, and by 2030 there are likely to be over 10,000.”

Genetic counseling within the VA has also grown rapidly. In 2010, Harzfeld said, about 737 veterans were referred for the service. In 2020, the number was about 10,000, with about half referred for personal or family history of cancer.

The VA has 18 genetic counselors, not all of whom are actively seeing patients or working full time, she said. “Per the National Society of Genetic Counselors, there's one clinical genetic counselor per 100,000 people in the general population,” she said. “It's one for about 474,000 in the VA.”

Wait times for genetic counseling within the VA exceed Mission Act standards outside of urgent referrals in matters such as surgical or medical management, she said. “We usually see those patients within a week, but other folks have to wait or are referred into the community. It remains unclear how many of our patients could access care easily in the community or what the wait times at any individual VA will be.”

Fortunately, she said, telemedicine has increased access to genetic counseling within the general population and the VA, Harzfeld said. “A recent systematic evidence review found providing genetic counseling via video or telephone is comparable to in-person care, it increases access and it's likely feasible and acceptable to major stakeholders. It's worth noting that the data in this evidence review was collected prior to COVID-19 when fewer programs were using telehealth.”

Genetic counseling works especially well via telehealth because counselors don’t perform physical examinations, she said. “Prior to COVID, service probably saw maybe 4 VVC [VA Video Connect] appointments per month for genetic counseling. Now, VVC makes up about 70% of our new patient encounters. About 25% are telephone and about 5% are clinical video telehealth where the veteran goes into their clinic to be seated in front of the machine.”

Research has suggested that non-White patients are 40 to 50% less likely to be referred to telehealth for genetic counseling vs. in-person encounters, she said, although women in general (including black women) are more likely to be referred.

Harzfeld highlighted several challenges facing genetic counseling in the VA. She notes that contracted laboratories aren’t “really set up to be experts in germline genetic testing, so they’re not as nimble, and their test catalogs are not most likely going to be as comprehensive enough for what is needed.” Also, she said, “test ordering can be quite burdensome.”

“We need to continue working with various partners to increase access and the ease of ordering genetic testing,” she said.

Hartzfeld reports no disclosures.

The U.S. Food and Drug Administration has granted accelerated approval to tisotumab vedotin-tftv (Tivdak, Seagen/Genmab) for the treatment of adult patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy.

There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.

In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”

“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.

Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
 

Details of clinical trial data

The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.

The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.

All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.

The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.

The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.

Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.

Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.

The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
 

Confirmatory trial underway

Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has granted accelerated approval to tisotumab vedotin-tftv (Tivdak, Seagen/Genmab) for the treatment of adult patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy.

There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.

In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”

“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.

Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
 

Details of clinical trial data

The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.

The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.

All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.

The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.

The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.

Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.

Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.

The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
 

Confirmatory trial underway

Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has granted accelerated approval to tisotumab vedotin-tftv (Tivdak, Seagen/Genmab) for the treatment of adult patients with recurrent or metastatic cervical cancer who have experienced disease progression on or after chemotherapy.

There is currently no standard option for these patients. The mainstay of therapy in this setting is monotherapy with chemotherapy, but the benefit-risk profiles are poor, and overall response rates (ORRs) are less than 15%.

In the clinical trial that led to the accelerated approval, tisotumab vedotin-tftv yielded an ORR of 24%, which an expert not connected with the trial said was “impressive.”

“Tivdak’s approval as a monotherapy in the U.S. is an important milestone for women with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, as they are in need of a new treatment option and we look forward to making it available to them,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.

Tisotumab vedotin is an antibody–drug conjugate: A human monoclonal antibody directed against tissue factor, which is highly expressed on many solid tumors, is attached to the microtubule-disrupting agent monomethyl auristatin E.
 

Details of clinical trial data

The accelerated approval was based on the results of the innovaTV 204, an open-label, multicenter, single-arm clinical trial, which was published online on April 9 in The Lancet Oncology, as reported at the time.

The trial included 101 women with recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer whose disease had progressed with or after doublet chemotherapy with bevacizumab (if eligible by local standards) and who had received two or fewer previous systemic regimens for recurrent or metastatic disease.

All patients received tisotumab vendotin intravenously at a dose of 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity.

The confirmed ORR was 24% and included seven (7%) complete responses and 17 (17%) partial responses.

The disease control rate was 72%, and the median duration of response was 8.3 months. The median progression-free survival was 4.2 months; the 6-month progression-free survival rate was 30%.

Median overall survival (OS) was 12.1 months. OS rates were 79% at 6 months and 51% at 12 months.

Overall, the safety profile with tisotumab vedotin was manageable, the trialists reported. The most common treatment-related adverse events were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Adverse events of grade 3 or higher were reported by 28% of patients and included neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). One patient died as a result of septic shock that was considered by the investigators to be related to therapy.

The new product labeling includes a boxed warning for ocular toxicity. It notes that tisotumab vedotin “caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration.” It recommends that clinicians conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated and that patients adhere to premedication and required eye care before, during, and after infusion.
 

Confirmatory trial underway

Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

The confirmatory trial for tisotumab vedotin is already underway: The global phase 3 innovaTV 301 trial began in January 2021. It will compare tisotumab vendotin to chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) for patients with recurrent or metastatic cervical cancer who have received one or two prior lines of systemic therapy.

A version of this article first appeared on Medscape.com.

The US Department of Veterans Affairs (VA) Northeast Ohio Healthcare System has been eaching out directly by postal mail to hundreds of veterans with cancer who may have been exposed to Agent Orange or contaminated water at Camp Lejeune in North Carolina. Advocates say they’ve connected dozens to “service-connected” benefits that pay for 100% of the veterans’ care and can potentially provide support to their spouses after they pass away.

The details and outcomes of the outreach project were presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

“Once you get a devastating diagnosis like cancer, you’ve got enough going on in your head. You shouldn’t have to worry about what the next step is in the benefit process,” said VA Northeast Ohio Healthcare System outreach coordinator Willie J. Berry in an interview. “We want you to focus on your care and not have to worry about anything else.”

Agent Orange, made up of 2,3,7,8-tetrachlorodibenzo-p-dioxin, was used to defoliate forests and kill crops during the Vietnam War. Through “100% service connection” the VA fully covers benefits for certain cancers and other diseases for veterans who are considered to have been exposed to Agent Orange in Vietnam and elsewhere.

Veterans do not need to pay copays in these cases, Berry said, and care outside the VA may be fully funded once arrangements are made.

The VA also fully covers benefits for a similar list of diseases, also including some types of cancer, for veterans who are considered to have been exposed to a contaminated water supply at Camp Lejeune in the early 1980s.

Vietnam War veterans may not be aware of the Agent Orange benefits due to a negative perception of the VA, Berry said. “They were treated poorly [by the VA] and didn’t want to have anything to do with it.”

In the first phase of the project, the VA Northeast Ohio Healthcare System tried to reach potentially eligible veterans with both cancer and possible Agent Orange exposure via phone. Seventy veterans were referred to outreach coordinators, and 16 received 100% service connection after 6 months. The latter number later grew to 34.

“The most inefficient thing were doing was calling veterans one by one,” Berry said. “We felt a mailer would be more efficient in order to reach more people.”

For the second phase, in 2021, coordinators sent informational “Dear veteran” mailers to 427 veterans with cancer who may be eligible for special Agent Orange/Camp Lejeune benefits based on their service history.

The Agent Orange letters began this way: “Through a recent medical diagnosis, VA has identified you as possibly being impacted by a change in Agent Orange Exposure legislation.” The letters then list the eligible conditions, which as of 2021 now include bladder cancer, hyperthyroidism and parkinsonism.

The letters also note that “claims often enhance a veteran’s VA compensation and reduce their cost of care. Additionally, if a veteran were to succumb to a diagnosis that they were service connected for, their spouse might be able to receive both VA health care (until the age of Medicare eligibility) as well as financial benefits for the rest of their life.”

If veterans were terminally ill, the application process for the special benefits could be expedited, Berry said. The number of veterans who received 100% service connection in the second phase of the project was not provided.

No study funding is reported. Berry has no disclosures.

The US Department of Veterans Affairs (VA) Northeast Ohio Healthcare System has been eaching out directly by postal mail to hundreds of veterans with cancer who may have been exposed to Agent Orange or contaminated water at Camp Lejeune in North Carolina. Advocates say they’ve connected dozens to “service-connected” benefits that pay for 100% of the veterans’ care and can potentially provide support to their spouses after they pass away.

The details and outcomes of the outreach project were presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

“Once you get a devastating diagnosis like cancer, you’ve got enough going on in your head. You shouldn’t have to worry about what the next step is in the benefit process,” said VA Northeast Ohio Healthcare System outreach coordinator Willie J. Berry in an interview. “We want you to focus on your care and not have to worry about anything else.”

Agent Orange, made up of 2,3,7,8-tetrachlorodibenzo-p-dioxin, was used to defoliate forests and kill crops during the Vietnam War. Through “100% service connection” the VA fully covers benefits for certain cancers and other diseases for veterans who are considered to have been exposed to Agent Orange in Vietnam and elsewhere.

Veterans do not need to pay copays in these cases, Berry said, and care outside the VA may be fully funded once arrangements are made.

The VA also fully covers benefits for a similar list of diseases, also including some types of cancer, for veterans who are considered to have been exposed to a contaminated water supply at Camp Lejeune in the early 1980s.

Vietnam War veterans may not be aware of the Agent Orange benefits due to a negative perception of the VA, Berry said. “They were treated poorly [by the VA] and didn’t want to have anything to do with it.”

In the first phase of the project, the VA Northeast Ohio Healthcare System tried to reach potentially eligible veterans with both cancer and possible Agent Orange exposure via phone. Seventy veterans were referred to outreach coordinators, and 16 received 100% service connection after 6 months. The latter number later grew to 34.

“The most inefficient thing were doing was calling veterans one by one,” Berry said. “We felt a mailer would be more efficient in order to reach more people.”

For the second phase, in 2021, coordinators sent informational “Dear veteran” mailers to 427 veterans with cancer who may be eligible for special Agent Orange/Camp Lejeune benefits based on their service history.

The Agent Orange letters began this way: “Through a recent medical diagnosis, VA has identified you as possibly being impacted by a change in Agent Orange Exposure legislation.” The letters then list the eligible conditions, which as of 2021 now include bladder cancer, hyperthyroidism and parkinsonism.

The letters also note that “claims often enhance a veteran’s VA compensation and reduce their cost of care. Additionally, if a veteran were to succumb to a diagnosis that they were service connected for, their spouse might be able to receive both VA health care (until the age of Medicare eligibility) as well as financial benefits for the rest of their life.”

If veterans were terminally ill, the application process for the special benefits could be expedited, Berry said. The number of veterans who received 100% service connection in the second phase of the project was not provided.

No study funding is reported. Berry has no disclosures.

The US Department of Veterans Affairs (VA) Northeast Ohio Healthcare System has been eaching out directly by postal mail to hundreds of veterans with cancer who may have been exposed to Agent Orange or contaminated water at Camp Lejeune in North Carolina. Advocates say they’ve connected dozens to “service-connected” benefits that pay for 100% of the veterans’ care and can potentially provide support to their spouses after they pass away.

The details and outcomes of the outreach project were presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and in person in Denver, Colorado, from September 24 to September 26, 2021.

“Once you get a devastating diagnosis like cancer, you’ve got enough going on in your head. You shouldn’t have to worry about what the next step is in the benefit process,” said VA Northeast Ohio Healthcare System outreach coordinator Willie J. Berry in an interview. “We want you to focus on your care and not have to worry about anything else.”

Agent Orange, made up of 2,3,7,8-tetrachlorodibenzo-p-dioxin, was used to defoliate forests and kill crops during the Vietnam War. Through “100% service connection” the VA fully covers benefits for certain cancers and other diseases for veterans who are considered to have been exposed to Agent Orange in Vietnam and elsewhere.

Veterans do not need to pay copays in these cases, Berry said, and care outside the VA may be fully funded once arrangements are made.

The VA also fully covers benefits for a similar list of diseases, also including some types of cancer, for veterans who are considered to have been exposed to a contaminated water supply at Camp Lejeune in the early 1980s.

Vietnam War veterans may not be aware of the Agent Orange benefits due to a negative perception of the VA, Berry said. “They were treated poorly [by the VA] and didn’t want to have anything to do with it.”

In the first phase of the project, the VA Northeast Ohio Healthcare System tried to reach potentially eligible veterans with both cancer and possible Agent Orange exposure via phone. Seventy veterans were referred to outreach coordinators, and 16 received 100% service connection after 6 months. The latter number later grew to 34.

“The most inefficient thing were doing was calling veterans one by one,” Berry said. “We felt a mailer would be more efficient in order to reach more people.”

For the second phase, in 2021, coordinators sent informational “Dear veteran” mailers to 427 veterans with cancer who may be eligible for special Agent Orange/Camp Lejeune benefits based on their service history.

The Agent Orange letters began this way: “Through a recent medical diagnosis, VA has identified you as possibly being impacted by a change in Agent Orange Exposure legislation.” The letters then list the eligible conditions, which as of 2021 now include bladder cancer, hyperthyroidism and parkinsonism.

The letters also note that “claims often enhance a veteran’s VA compensation and reduce their cost of care. Additionally, if a veteran were to succumb to a diagnosis that they were service connected for, their spouse might be able to receive both VA health care (until the age of Medicare eligibility) as well as financial benefits for the rest of their life.”

If veterans were terminally ill, the application process for the special benefits could be expedited, Berry said. The number of veterans who received 100% service connection in the second phase of the project was not provided.

No study funding is reported. Berry has no disclosures.

Community outreach coordinators identified Veterans who were not aware of their entitlement to service-connected benefits. Veterans were also unaware of the importance of adding new presumptive diagnoses to their existing service connection and were unaware of new conditions that were added to the presumptive lists. Many Veterans, unaware of the Agent Orange/Camp Lejeune presumptive conditions, were paying out of pocket for their oncology care. A project was developed between community outreach and oncology to identify, and contact Veterans newly diagnosed with cancers on the presumptive list for Vietnam and Camp Lejeune. The goals for the project were to: Increase presumptive condition awareness, assist Veterans in navigating the VHA, VBA and VSC (Veteran Service Commission) and provide a VA resource for the Veterans for assistance. Oncology team reviewed the cancer registry each month and identified Veterans who served during the Vietnam Era or the Marine Corps and contacted them to screen for military history. If a Veteran met the time and location qualifications, the Veteran was referred to the community outreach coordinators. The coordinators then further screened the Veterans for eligibility, assisted the Veterans in initiating their claims applications and connected the Veterans with their local VSC. At the six month follow up, 74 Veterans had been referred to community outreach, and 16 Veterans had received 100% service connection. It is important to note, the benefits application process can take several months to complete under normal circumstances. Since implementation the project has been revised. The project team developed mailers to alert Veterans of: Potential benefits eligibility, importance for filing claims, contact information for their local VSC and contact information for VA Outreach for additional assistance. Informatics was recruited to assist with identifying Veterans who met the service criteria and providing their addresses. The Veterans identified were then sent mailers, which expedited the process, allowing the project team to reach more Veterans in a shorter timeframe. Since project initiation, 74 Veterans were contacted directly by outreach coordinators, 273 mailers have been sent to potentially eligible Veterans, and 34 have received 100% service connection to date. al center will continue this practice moving forward.

Community outreach coordinators identified Veterans who were not aware of their entitlement to service-connected benefits. Veterans were also unaware of the importance of adding new presumptive diagnoses to their existing service connection and were unaware of new conditions that were added to the presumptive lists. Many Veterans, unaware of the Agent Orange/Camp Lejeune presumptive conditions, were paying out of pocket for their oncology care. A project was developed between community outreach and oncology to identify, and contact Veterans newly diagnosed with cancers on the presumptive list for Vietnam and Camp Lejeune. The goals for the project were to: Increase presumptive condition awareness, assist Veterans in navigating the VHA, VBA and VSC (Veteran Service Commission) and provide a VA resource for the Veterans for assistance. Oncology team reviewed the cancer registry each month and identified Veterans who served during the Vietnam Era or the Marine Corps and contacted them to screen for military history. If a Veteran met the time and location qualifications, the Veteran was referred to the community outreach coordinators. The coordinators then further screened the Veterans for eligibility, assisted the Veterans in initiating their claims applications and connected the Veterans with their local VSC. At the six month follow up, 74 Veterans had been referred to community outreach, and 16 Veterans had received 100% service connection. It is important to note, the benefits application process can take several months to complete under normal circumstances. Since implementation the project has been revised. The project team developed mailers to alert Veterans of: Potential benefits eligibility, importance for filing claims, contact information for their local VSC and contact information for VA Outreach for additional assistance. Informatics was recruited to assist with identifying Veterans who met the service criteria and providing their addresses. The Veterans identified were then sent mailers, which expedited the process, allowing the project team to reach more Veterans in a shorter timeframe. Since project initiation, 74 Veterans were contacted directly by outreach coordinators, 273 mailers have been sent to potentially eligible Veterans, and 34 have received 100% service connection to date. al center will continue this practice moving forward.

Community outreach coordinators identified Veterans who were not aware of their entitlement to service-connected benefits. Veterans were also unaware of the importance of adding new presumptive diagnoses to their existing service connection and were unaware of new conditions that were added to the presumptive lists. Many Veterans, unaware of the Agent Orange/Camp Lejeune presumptive conditions, were paying out of pocket for their oncology care. A project was developed between community outreach and oncology to identify, and contact Veterans newly diagnosed with cancers on the presumptive list for Vietnam and Camp Lejeune. The goals for the project were to: Increase presumptive condition awareness, assist Veterans in navigating the VHA, VBA and VSC (Veteran Service Commission) and provide a VA resource for the Veterans for assistance. Oncology team reviewed the cancer registry each month and identified Veterans who served during the Vietnam Era or the Marine Corps and contacted them to screen for military history. If a Veteran met the time and location qualifications, the Veteran was referred to the community outreach coordinators. The coordinators then further screened the Veterans for eligibility, assisted the Veterans in initiating their claims applications and connected the Veterans with their local VSC. At the six month follow up, 74 Veterans had been referred to community outreach, and 16 Veterans had received 100% service connection. It is important to note, the benefits application process can take several months to complete under normal circumstances. Since implementation the project has been revised. The project team developed mailers to alert Veterans of: Potential benefits eligibility, importance for filing claims, contact information for their local VSC and contact information for VA Outreach for additional assistance. Informatics was recruited to assist with identifying Veterans who met the service criteria and providing their addresses. The Veterans identified were then sent mailers, which expedited the process, allowing the project team to reach more Veterans in a shorter timeframe. Since project initiation, 74 Veterans were contacted directly by outreach coordinators, 273 mailers have been sent to potentially eligible Veterans, and 34 have received 100% service connection to date. al center will continue this practice moving forward.

In a recent inpatient service block, I was seeing patients alongside a resident I had gotten to know well. We were consulted on a patient with metastatic head and neck cancer who had not sought care for over a year.

When the patient presented, his voice was raspy and he could not swallow. He had lost 40 pounds. In addition to his locally advanced disease, his lungs were riddled with metastatic lesions.

When we left the room, the resident and I went to speak to the patient’s primary team, and he began to relay our recommendations.

The first words out of his mouth were, “Well, it’s pretty clear he’s going to die.”

The statement took me aback. I wasn’t alarmed by the accuracy of what he had said. The patient was obviously not doing well, and he ended up dying soon after this visit.

It was more the abrupt manner in which the resident had spoken about death. The brusque phrasing felt atypical coming from the otherwise gentle-hearted trainee. He wasn’t referring to a faceless person. We had just seen the man a few minutes ago and heard his personal struggles. I tried to see if anyone else on the team was caught off guard, but everyone was taking notes or continuing to listen, seemingly undeterred.
 

Oncologists’ ‘locker room talk’

I’ve noticed that “locker room talk” about death happens often. Phrases like “he’s definitely not going to do well” and “his life expectancy is poor” make their way into oncologists’ daily language. Thinking back on my own interactions, I realize I am also guilty of discussing death in this way.

And now, with the COVID pandemic forcing most of our tumor boards to go virtual, I find this locker room talk comes even more readily; phrases like “this patient is going to die” are often passed around flippantly, as if saying so will help ease the tension. During these interactions, my colleagues and I rarely acknowledge the seriousness of what a patient death will do to their family and loved ones – or what losing a patient whom we’ve known for years may do to our own psyche.

This language can even creep into how we speak with patients. We are often taught to offer prognoses coldly, ensuring that patients have a clear sense of how long they have left and to help inform their treatment choices. And yet, this training does not necessarily align with what patients want and need. For instance, in a recent survey of patients with chronic obstructive pulmonary disease, patients consistently rated physicians poorly at discussing prognosis, what dying might be like, as well as spirituality and religion.

But at the same time, these matter-of-fact statements about death probably help protect us. Death is a routine, inevitable part of an oncologist’s life, and over time, oncology training and practice hardens us to it. During medical school, I remember that a patient dying would trigger immediate reflection, sadness, and conversation with our peers. Now, unless I know a patient well, I find myself rarely reflecting on the patient behind the facts. This evolution is natural for an oncologist: If you don’t develop a tough skin about death, you may become overwhelmed with the frequency of it.

The COVID pandemic has amped our hardness toward death into overdrive. Whether we are in the intensive care unit or simply viewing death rates during the most recent COVID Delta wave, many of us cope by disassociating a face from a name.
 

Making time for reflection

But taking time to reflect can be therapeutic.

I recently referred a patient with metastatic prostate cancer for a phase 1 trial at an outside institution. He was one of the first patients in my genitourinary malignancies clinic when I started as an attending. The patient had progressed through several lines of therapy and was being referred for an investigational phase 1 therapy. We had discussed hospice referral, and the patient was ready for it if this therapy didn’t work out.

I did not see or hear from the man while he was on the trial. A few months later, however, the principal investigator of the trial called me to let me know the patient had progressed through the agent, suffering from significant urinary obstruction, and he was on hospice. “Unfortunately,” the investigator told me, “he’s not going to live much longer.”

When I checked in with the hospice, the patient had died.

I was surprised again at how matter-of-fact the discussion of death had been. But I was even more surprised by my own reaction. Despite the relationship I had formed with the patient, I did not feel much when I heard he had died. I didn’t have time to process the news in the moment. It was time to move on to the next patient.

It was only later, when I called the patient’s family, that I allowed my emotions to flood in. I told his family how grateful I was to know him, how strong he’d been. The patient’s family and I talked about the human, not his passing. It felt good.
 

Abandoning locker room talk

So how do we change how we talk about death? I don’t think the answer is massive educational programs or passing responsibility for advance care planning onto palliative care specialists. The change needs to be driven by individual oncologists. We can call out discussions of death that make us uncomfortable, gently reminding each other that we’re talking about a human life.

We can learn from our palliative care colleagues; their conversations about death routinely include a patient’s support system and personal stories. Palliative care doctors always refer to the patient by name, which helps humanize the person behind the chart.

We can emphasize a feeling of hope, a sentiment that may also be therapeutic to our patients. Even when a patient is dying, there is always something to be done. We can comfort their family, explaining what brought us to this point and how sorry we are that this is happening. We can provide options for symptom control and help patients manage those symptoms.

And we can allow ourselves to talk about how much a death affects us. We can acknowledge how much it sucks that a patient is going to die, how challenging that will be to his/her family, and how we wish it could have ended differently.

Subtle changes like these will improve our own ability to process and discuss death and will ultimately lead to better relationships with our patients. But it starts with eliminating the “locker room talk” of how we discuss death.
 

Ravi B. Parikh, MD, MPP, is a medical oncologist and faculty member at the University of Pennsylvania and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care (C-TAC). He has served as a director, officer, partner, employee, adviser, consultant, or trustee for GNS Healthcare, Nanology, and Cancer Study Group, and he has received research grant from Embedded Healthcare, Veterans Administration, PCF, National Palliative Care Research Center, and MUSC. A version of this article first appeared on Medscape.com.

In a recent inpatient service block, I was seeing patients alongside a resident I had gotten to know well. We were consulted on a patient with metastatic head and neck cancer who had not sought care for over a year.

When the patient presented, his voice was raspy and he could not swallow. He had lost 40 pounds. In addition to his locally advanced disease, his lungs were riddled with metastatic lesions.

When we left the room, the resident and I went to speak to the patient’s primary team, and he began to relay our recommendations.

The first words out of his mouth were, “Well, it’s pretty clear he’s going to die.”

The statement took me aback. I wasn’t alarmed by the accuracy of what he had said. The patient was obviously not doing well, and he ended up dying soon after this visit.

It was more the abrupt manner in which the resident had spoken about death. The brusque phrasing felt atypical coming from the otherwise gentle-hearted trainee. He wasn’t referring to a faceless person. We had just seen the man a few minutes ago and heard his personal struggles. I tried to see if anyone else on the team was caught off guard, but everyone was taking notes or continuing to listen, seemingly undeterred.
 

Oncologists’ ‘locker room talk’

I’ve noticed that “locker room talk” about death happens often. Phrases like “he’s definitely not going to do well” and “his life expectancy is poor” make their way into oncologists’ daily language. Thinking back on my own interactions, I realize I am also guilty of discussing death in this way.

And now, with the COVID pandemic forcing most of our tumor boards to go virtual, I find this locker room talk comes even more readily; phrases like “this patient is going to die” are often passed around flippantly, as if saying so will help ease the tension. During these interactions, my colleagues and I rarely acknowledge the seriousness of what a patient death will do to their family and loved ones – or what losing a patient whom we’ve known for years may do to our own psyche.

This language can even creep into how we speak with patients. We are often taught to offer prognoses coldly, ensuring that patients have a clear sense of how long they have left and to help inform their treatment choices. And yet, this training does not necessarily align with what patients want and need. For instance, in a recent survey of patients with chronic obstructive pulmonary disease, patients consistently rated physicians poorly at discussing prognosis, what dying might be like, as well as spirituality and religion.

But at the same time, these matter-of-fact statements about death probably help protect us. Death is a routine, inevitable part of an oncologist’s life, and over time, oncology training and practice hardens us to it. During medical school, I remember that a patient dying would trigger immediate reflection, sadness, and conversation with our peers. Now, unless I know a patient well, I find myself rarely reflecting on the patient behind the facts. This evolution is natural for an oncologist: If you don’t develop a tough skin about death, you may become overwhelmed with the frequency of it.

The COVID pandemic has amped our hardness toward death into overdrive. Whether we are in the intensive care unit or simply viewing death rates during the most recent COVID Delta wave, many of us cope by disassociating a face from a name.
 

Making time for reflection

But taking time to reflect can be therapeutic.

I recently referred a patient with metastatic prostate cancer for a phase 1 trial at an outside institution. He was one of the first patients in my genitourinary malignancies clinic when I started as an attending. The patient had progressed through several lines of therapy and was being referred for an investigational phase 1 therapy. We had discussed hospice referral, and the patient was ready for it if this therapy didn’t work out.

I did not see or hear from the man while he was on the trial. A few months later, however, the principal investigator of the trial called me to let me know the patient had progressed through the agent, suffering from significant urinary obstruction, and he was on hospice. “Unfortunately,” the investigator told me, “he’s not going to live much longer.”

When I checked in with the hospice, the patient had died.

I was surprised again at how matter-of-fact the discussion of death had been. But I was even more surprised by my own reaction. Despite the relationship I had formed with the patient, I did not feel much when I heard he had died. I didn’t have time to process the news in the moment. It was time to move on to the next patient.

It was only later, when I called the patient’s family, that I allowed my emotions to flood in. I told his family how grateful I was to know him, how strong he’d been. The patient’s family and I talked about the human, not his passing. It felt good.
 

Abandoning locker room talk

So how do we change how we talk about death? I don’t think the answer is massive educational programs or passing responsibility for advance care planning onto palliative care specialists. The change needs to be driven by individual oncologists. We can call out discussions of death that make us uncomfortable, gently reminding each other that we’re talking about a human life.

We can learn from our palliative care colleagues; their conversations about death routinely include a patient’s support system and personal stories. Palliative care doctors always refer to the patient by name, which helps humanize the person behind the chart.

We can emphasize a feeling of hope, a sentiment that may also be therapeutic to our patients. Even when a patient is dying, there is always something to be done. We can comfort their family, explaining what brought us to this point and how sorry we are that this is happening. We can provide options for symptom control and help patients manage those symptoms.

And we can allow ourselves to talk about how much a death affects us. We can acknowledge how much it sucks that a patient is going to die, how challenging that will be to his/her family, and how we wish it could have ended differently.

Subtle changes like these will improve our own ability to process and discuss death and will ultimately lead to better relationships with our patients. But it starts with eliminating the “locker room talk” of how we discuss death.
 

Ravi B. Parikh, MD, MPP, is a medical oncologist and faculty member at the University of Pennsylvania and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care (C-TAC). He has served as a director, officer, partner, employee, adviser, consultant, or trustee for GNS Healthcare, Nanology, and Cancer Study Group, and he has received research grant from Embedded Healthcare, Veterans Administration, PCF, National Palliative Care Research Center, and MUSC. A version of this article first appeared on Medscape.com.

In a recent inpatient service block, I was seeing patients alongside a resident I had gotten to know well. We were consulted on a patient with metastatic head and neck cancer who had not sought care for over a year.

When the patient presented, his voice was raspy and he could not swallow. He had lost 40 pounds. In addition to his locally advanced disease, his lungs were riddled with metastatic lesions.

When we left the room, the resident and I went to speak to the patient’s primary team, and he began to relay our recommendations.

The first words out of his mouth were, “Well, it’s pretty clear he’s going to die.”

The statement took me aback. I wasn’t alarmed by the accuracy of what he had said. The patient was obviously not doing well, and he ended up dying soon after this visit.

It was more the abrupt manner in which the resident had spoken about death. The brusque phrasing felt atypical coming from the otherwise gentle-hearted trainee. He wasn’t referring to a faceless person. We had just seen the man a few minutes ago and heard his personal struggles. I tried to see if anyone else on the team was caught off guard, but everyone was taking notes or continuing to listen, seemingly undeterred.
 

Oncologists’ ‘locker room talk’

I’ve noticed that “locker room talk” about death happens often. Phrases like “he’s definitely not going to do well” and “his life expectancy is poor” make their way into oncologists’ daily language. Thinking back on my own interactions, I realize I am also guilty of discussing death in this way.

And now, with the COVID pandemic forcing most of our tumor boards to go virtual, I find this locker room talk comes even more readily; phrases like “this patient is going to die” are often passed around flippantly, as if saying so will help ease the tension. During these interactions, my colleagues and I rarely acknowledge the seriousness of what a patient death will do to their family and loved ones – or what losing a patient whom we’ve known for years may do to our own psyche.

This language can even creep into how we speak with patients. We are often taught to offer prognoses coldly, ensuring that patients have a clear sense of how long they have left and to help inform their treatment choices. And yet, this training does not necessarily align with what patients want and need. For instance, in a recent survey of patients with chronic obstructive pulmonary disease, patients consistently rated physicians poorly at discussing prognosis, what dying might be like, as well as spirituality and religion.

But at the same time, these matter-of-fact statements about death probably help protect us. Death is a routine, inevitable part of an oncologist’s life, and over time, oncology training and practice hardens us to it. During medical school, I remember that a patient dying would trigger immediate reflection, sadness, and conversation with our peers. Now, unless I know a patient well, I find myself rarely reflecting on the patient behind the facts. This evolution is natural for an oncologist: If you don’t develop a tough skin about death, you may become overwhelmed with the frequency of it.

The COVID pandemic has amped our hardness toward death into overdrive. Whether we are in the intensive care unit or simply viewing death rates during the most recent COVID Delta wave, many of us cope by disassociating a face from a name.
 

Making time for reflection

But taking time to reflect can be therapeutic.

I recently referred a patient with metastatic prostate cancer for a phase 1 trial at an outside institution. He was one of the first patients in my genitourinary malignancies clinic when I started as an attending. The patient had progressed through several lines of therapy and was being referred for an investigational phase 1 therapy. We had discussed hospice referral, and the patient was ready for it if this therapy didn’t work out.

I did not see or hear from the man while he was on the trial. A few months later, however, the principal investigator of the trial called me to let me know the patient had progressed through the agent, suffering from significant urinary obstruction, and he was on hospice. “Unfortunately,” the investigator told me, “he’s not going to live much longer.”

When I checked in with the hospice, the patient had died.

I was surprised again at how matter-of-fact the discussion of death had been. But I was even more surprised by my own reaction. Despite the relationship I had formed with the patient, I did not feel much when I heard he had died. I didn’t have time to process the news in the moment. It was time to move on to the next patient.

It was only later, when I called the patient’s family, that I allowed my emotions to flood in. I told his family how grateful I was to know him, how strong he’d been. The patient’s family and I talked about the human, not his passing. It felt good.
 

Abandoning locker room talk

So how do we change how we talk about death? I don’t think the answer is massive educational programs or passing responsibility for advance care planning onto palliative care specialists. The change needs to be driven by individual oncologists. We can call out discussions of death that make us uncomfortable, gently reminding each other that we’re talking about a human life.

We can learn from our palliative care colleagues; their conversations about death routinely include a patient’s support system and personal stories. Palliative care doctors always refer to the patient by name, which helps humanize the person behind the chart.

We can emphasize a feeling of hope, a sentiment that may also be therapeutic to our patients. Even when a patient is dying, there is always something to be done. We can comfort their family, explaining what brought us to this point and how sorry we are that this is happening. We can provide options for symptom control and help patients manage those symptoms.

And we can allow ourselves to talk about how much a death affects us. We can acknowledge how much it sucks that a patient is going to die, how challenging that will be to his/her family, and how we wish it could have ended differently.

Subtle changes like these will improve our own ability to process and discuss death and will ultimately lead to better relationships with our patients. But it starts with eliminating the “locker room talk” of how we discuss death.
 

Ravi B. Parikh, MD, MPP, is a medical oncologist and faculty member at the University of Pennsylvania and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care (C-TAC). He has served as a director, officer, partner, employee, adviser, consultant, or trustee for GNS Healthcare, Nanology, and Cancer Study Group, and he has received research grant from Embedded Healthcare, Veterans Administration, PCF, National Palliative Care Research Center, and MUSC. A version of this article first appeared on Medscape.com.

Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.

Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.

“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”

Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.

The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.

“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”

Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”

The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”

Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”

The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”

However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”

“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”

She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.

Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”

No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.

Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.

Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.

“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”

Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.

The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.

“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”

Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”

The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”

Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”

The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”

However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”

“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”

She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.

Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”

No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.

Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.

Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.

“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”

Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.

The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.

“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”

Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”

The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”

Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”

The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”

However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”

“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”

She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.

Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”

No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.