Patient & Survivor Care

In this interview, Dr David Henry and Dr Maura Sammon discuss some of the most common immunotherapy-related side effects – lung, gastrointestinal, rash, and endocrine-related problems – and Dr Sammon describes in detail how physicians in the ED would triage and treat the patient. However, the overarching takeaway is the importance of communication: first, between the oncologist and patient, so that the patient is aware of these nuances in advance of an emergency, and second, between the ED physician and the treating oncologist soon after the patient has presented and undergone an initial assessment.

Dr Henry is Editor-in-Chief of  the JCSO, and Dr Sammon is at the Lewis Katz School of Medicine, Temple University, in Philadelphia, Pennsylvania

Listen here:

In this interview, Dr David Henry and Dr Maura Sammon discuss some of the most common immunotherapy-related side effects – lung, gastrointestinal, rash, and endocrine-related problems – and Dr Sammon describes in detail how physicians in the ED would triage and treat the patient. However, the overarching takeaway is the importance of communication: first, between the oncologist and patient, so that the patient is aware of these nuances in advance of an emergency, and second, between the ED physician and the treating oncologist soon after the patient has presented and undergone an initial assessment.

Dr Henry is Editor-in-Chief of  the JCSO, and Dr Sammon is at the Lewis Katz School of Medicine, Temple University, in Philadelphia, Pennsylvania

Listen here:

In this interview, Dr David Henry and Dr Maura Sammon discuss some of the most common immunotherapy-related side effects – lung, gastrointestinal, rash, and endocrine-related problems – and Dr Sammon describes in detail how physicians in the ED would triage and treat the patient. However, the overarching takeaway is the importance of communication: first, between the oncologist and patient, so that the patient is aware of these nuances in advance of an emergency, and second, between the ED physician and the treating oncologist soon after the patient has presented and undergone an initial assessment.

Dr Henry is Editor-in-Chief of  the JCSO, and Dr Sammon is at the Lewis Katz School of Medicine, Temple University, in Philadelphia, Pennsylvania

Listen here:

Adding more evidence to an ongoing debate, a large new study suggests that patients with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of developing heart failure, with older women at highest risk.

The study also found that most patients who took trastuzumab didn’t receive recommended cardiac screening.

The researchers said their findings are unique because they tracked both younger and older patients. “By examining the rates of both cardiac monitoring and cardiotoxicity, we could begin to address the controversial issue of whether cardiac monitoring is warranted in young breast cancer patients,” wrote Mariana Chavez-MacGregor, MD, MSC, of the University of Texas MD Anderson Cancer Center, and her associates. The report was published in JACC: Cardiovascular Imaging.

While Trastuzumab has boosted breast cancer survival rates for patients with HER2-positive tumors, it’s also raised concerns about cardiotoxicity that could be an indicator of subsequent congestive heart failure (Cochrane Database Syst Rev. 2014 Jun 12;(6):CD006242).

According to the new study, the risk of trastuzumab risk is linked to damage to cardiac myocytes that can cause reversible cardiotoxicity.

The prescribing information for trastuzumab advises patients to undergo cardiac monitoring before treatment with trastuzumab and every 3 months during treatment. Recommendations by medical organizations have varied.

Now, as a 2016 report put it, it’s “increasingly unclear” whether frequent routine monitoring is appropriate for all patients (J Clin Oncol. 2016 Apr 1;34[10]:1030-3).

For the current study, Dr. Chavez-MacGregor and her associates identified 16,456 adult women in the United States who were diagnosed with nonmetastatic invasive breast cancer from 2009 to 2014. Researchers tracked the group, with a median age of 56, through as late as 2015.

The women were treated with chemotherapy within 6 months of diagnosis, and 4,325 received trastuzumab.

Of all the subjects, 692 patients (4.2%) developed heart failure following chemotherapy. The rate among patients treated with trastuzumab was higher, at 8.3%, compared with 2.7% for those not treated with trastuzumab (P less than .001).

The researchers also looked at anthracycline users and found that they were slightly more likely to develop HF (4.6% vs. 4.0% among nonusers, P = .048).

Increased age boosted the risk of HF in the trastuzumab-treated patients, and the risk was highest in those treated with both anthracyclines and trastuzumab. Other factors linked to more risk were comorbidities, hypertension, and valve disease.

After adjusting for confounders, the researchers estimated that those treated with trastuzumab were 2.01 times more likely to develop HF (HR, 2.01; 95% confidence interval, 1.72-2.36), and those who took anthracycline were 1.53 times more likely (HR, 1.53; 95% CI, 1.30-1.80)

The researchers also examined medical records for evidence that subjects underwent cardiac screening at least once every 4 months, not 3 months, as the prescribing information recommends. The study team chose to focus on 4-month intervals “to compensate for differences in scheduling, resources, or levels of accessibility to medical care.”

Medical records suggest that 73.5% of patients who took trastuzumab underwent cardiac screening at the beginning of therapy, but only 46.2% continued to do so at least every 4 months.

An adjusted model linked more screening to the use of anthracyclines and taxanes, radiation treatment, and living in the Northeast vs. the West.

“HF was more frequently identified among patients undergoing recommended cardiac monitoring (10.4% compared with 6.5%, respectively; P less than.001), suggesting that, as more patients are screened, more patients are likely to be found having HF,” the researchers reported.

However, they added that “our sensitivity analysis using inpatient claims allowed us to determine that the HF identified using cardiac monitoring was not severe enough to require hospitalization and was likely asymptomatic. The clinical implications of the diagnosis of asymptomatic HF are hard to determine and are beyond the scope of this study.”

The researchers also noted that the findings suggest that screening has become more common in recent years.

“The number of cancer survivors is expected to increase over time, and we will continue to see patients develop treatment-related cardiotoxicity,” the researchers wrote. “Thus, more research, evidence-based guidelines, and tools for prediction of cancer treatment–related cardiotoxicity are needed.”

The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors reported grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors reported no disclosures.

SOURCE: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging. 2018 Aug;11[8]1084-93.

Adding more evidence to an ongoing debate, a large new study suggests that patients with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of developing heart failure, with older women at highest risk.

The study also found that most patients who took trastuzumab didn’t receive recommended cardiac screening.

The researchers said their findings are unique because they tracked both younger and older patients. “By examining the rates of both cardiac monitoring and cardiotoxicity, we could begin to address the controversial issue of whether cardiac monitoring is warranted in young breast cancer patients,” wrote Mariana Chavez-MacGregor, MD, MSC, of the University of Texas MD Anderson Cancer Center, and her associates. The report was published in JACC: Cardiovascular Imaging.

While Trastuzumab has boosted breast cancer survival rates for patients with HER2-positive tumors, it’s also raised concerns about cardiotoxicity that could be an indicator of subsequent congestive heart failure (Cochrane Database Syst Rev. 2014 Jun 12;(6):CD006242).

According to the new study, the risk of trastuzumab risk is linked to damage to cardiac myocytes that can cause reversible cardiotoxicity.

The prescribing information for trastuzumab advises patients to undergo cardiac monitoring before treatment with trastuzumab and every 3 months during treatment. Recommendations by medical organizations have varied.

Now, as a 2016 report put it, it’s “increasingly unclear” whether frequent routine monitoring is appropriate for all patients (J Clin Oncol. 2016 Apr 1;34[10]:1030-3).

For the current study, Dr. Chavez-MacGregor and her associates identified 16,456 adult women in the United States who were diagnosed with nonmetastatic invasive breast cancer from 2009 to 2014. Researchers tracked the group, with a median age of 56, through as late as 2015.

The women were treated with chemotherapy within 6 months of diagnosis, and 4,325 received trastuzumab.

Of all the subjects, 692 patients (4.2%) developed heart failure following chemotherapy. The rate among patients treated with trastuzumab was higher, at 8.3%, compared with 2.7% for those not treated with trastuzumab (P less than .001).

The researchers also looked at anthracycline users and found that they were slightly more likely to develop HF (4.6% vs. 4.0% among nonusers, P = .048).

Increased age boosted the risk of HF in the trastuzumab-treated patients, and the risk was highest in those treated with both anthracyclines and trastuzumab. Other factors linked to more risk were comorbidities, hypertension, and valve disease.

After adjusting for confounders, the researchers estimated that those treated with trastuzumab were 2.01 times more likely to develop HF (HR, 2.01; 95% confidence interval, 1.72-2.36), and those who took anthracycline were 1.53 times more likely (HR, 1.53; 95% CI, 1.30-1.80)

The researchers also examined medical records for evidence that subjects underwent cardiac screening at least once every 4 months, not 3 months, as the prescribing information recommends. The study team chose to focus on 4-month intervals “to compensate for differences in scheduling, resources, or levels of accessibility to medical care.”

Medical records suggest that 73.5% of patients who took trastuzumab underwent cardiac screening at the beginning of therapy, but only 46.2% continued to do so at least every 4 months.

An adjusted model linked more screening to the use of anthracyclines and taxanes, radiation treatment, and living in the Northeast vs. the West.

“HF was more frequently identified among patients undergoing recommended cardiac monitoring (10.4% compared with 6.5%, respectively; P less than.001), suggesting that, as more patients are screened, more patients are likely to be found having HF,” the researchers reported.

However, they added that “our sensitivity analysis using inpatient claims allowed us to determine that the HF identified using cardiac monitoring was not severe enough to require hospitalization and was likely asymptomatic. The clinical implications of the diagnosis of asymptomatic HF are hard to determine and are beyond the scope of this study.”

The researchers also noted that the findings suggest that screening has become more common in recent years.

“The number of cancer survivors is expected to increase over time, and we will continue to see patients develop treatment-related cardiotoxicity,” the researchers wrote. “Thus, more research, evidence-based guidelines, and tools for prediction of cancer treatment–related cardiotoxicity are needed.”

The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors reported grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors reported no disclosures.

SOURCE: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging. 2018 Aug;11[8]1084-93.

Adding more evidence to an ongoing debate, a large new study suggests that patients with breast cancer who take trastuzumab (Herceptin) may face double the adjusted risk of developing heart failure, with older women at highest risk.

The study also found that most patients who took trastuzumab didn’t receive recommended cardiac screening.

The researchers said their findings are unique because they tracked both younger and older patients. “By examining the rates of both cardiac monitoring and cardiotoxicity, we could begin to address the controversial issue of whether cardiac monitoring is warranted in young breast cancer patients,” wrote Mariana Chavez-MacGregor, MD, MSC, of the University of Texas MD Anderson Cancer Center, and her associates. The report was published in JACC: Cardiovascular Imaging.

While Trastuzumab has boosted breast cancer survival rates for patients with HER2-positive tumors, it’s also raised concerns about cardiotoxicity that could be an indicator of subsequent congestive heart failure (Cochrane Database Syst Rev. 2014 Jun 12;(6):CD006242).

According to the new study, the risk of trastuzumab risk is linked to damage to cardiac myocytes that can cause reversible cardiotoxicity.

The prescribing information for trastuzumab advises patients to undergo cardiac monitoring before treatment with trastuzumab and every 3 months during treatment. Recommendations by medical organizations have varied.

Now, as a 2016 report put it, it’s “increasingly unclear” whether frequent routine monitoring is appropriate for all patients (J Clin Oncol. 2016 Apr 1;34[10]:1030-3).

For the current study, Dr. Chavez-MacGregor and her associates identified 16,456 adult women in the United States who were diagnosed with nonmetastatic invasive breast cancer from 2009 to 2014. Researchers tracked the group, with a median age of 56, through as late as 2015.

The women were treated with chemotherapy within 6 months of diagnosis, and 4,325 received trastuzumab.

Of all the subjects, 692 patients (4.2%) developed heart failure following chemotherapy. The rate among patients treated with trastuzumab was higher, at 8.3%, compared with 2.7% for those not treated with trastuzumab (P less than .001).

The researchers also looked at anthracycline users and found that they were slightly more likely to develop HF (4.6% vs. 4.0% among nonusers, P = .048).

Increased age boosted the risk of HF in the trastuzumab-treated patients, and the risk was highest in those treated with both anthracyclines and trastuzumab. Other factors linked to more risk were comorbidities, hypertension, and valve disease.

After adjusting for confounders, the researchers estimated that those treated with trastuzumab were 2.01 times more likely to develop HF (HR, 2.01; 95% confidence interval, 1.72-2.36), and those who took anthracycline were 1.53 times more likely (HR, 1.53; 95% CI, 1.30-1.80)

The researchers also examined medical records for evidence that subjects underwent cardiac screening at least once every 4 months, not 3 months, as the prescribing information recommends. The study team chose to focus on 4-month intervals “to compensate for differences in scheduling, resources, or levels of accessibility to medical care.”

Medical records suggest that 73.5% of patients who took trastuzumab underwent cardiac screening at the beginning of therapy, but only 46.2% continued to do so at least every 4 months.

An adjusted model linked more screening to the use of anthracyclines and taxanes, radiation treatment, and living in the Northeast vs. the West.

“HF was more frequently identified among patients undergoing recommended cardiac monitoring (10.4% compared with 6.5%, respectively; P less than.001), suggesting that, as more patients are screened, more patients are likely to be found having HF,” the researchers reported.

However, they added that “our sensitivity analysis using inpatient claims allowed us to determine that the HF identified using cardiac monitoring was not severe enough to require hospitalization and was likely asymptomatic. The clinical implications of the diagnosis of asymptomatic HF are hard to determine and are beyond the scope of this study.”

The researchers also noted that the findings suggest that screening has become more common in recent years.

“The number of cancer survivors is expected to increase over time, and we will continue to see patients develop treatment-related cardiotoxicity,” the researchers wrote. “Thus, more research, evidence-based guidelines, and tools for prediction of cancer treatment–related cardiotoxicity are needed.”

The National Cancer Institute and Cancer Prevention and Research Institute of Texas funded the study. Two study authors reported grant funding from the Susan G. Komen Breast Cancer Foundation, and one reports consulting for Pfizer and Roche. The other authors reported no disclosures.

SOURCE: Chavez-MacGregor M et al. JACC: Cardiovasc Imaging. 2018 Aug;11[8]1084-93.

Lay health workers (LHWs) can improve documentation of cancer patients’ care preferences in the aftermath of their diagnosis, investigators report.

Physicians, palliative care workers, and other health professionals can help cancer patients understand their prognosis and establish end-of-life care preferences, but busy schedules and professional reluctance often prevent this. Nonclinical, nonprofessional LHWs often are employed to assist with screening and adherence, but little work has been done to use them in end-of-life care, Manali I. Patel, MD, MPH, and her associates wrote in JAMA Oncology.

To investigate their potential in this role, the researchers randomized 213 patients with stage 3 or 4 recurrent cancer to usual care or the LHW intervention, which included a 6-month structured program delivered by a single LHW who was enrolled in a part-time graduate health education program. The LHWs received an 80-hour online skills-based seminar and 4 weeks’ observation training with a palliative care team.

The LHWs helped patients with advanced care planning, including: education about goals of care, establishment of care preferences, establishment of a surrogate decision maker, creation of an advanced directive, and encouragement to discuss the patient’s care with the clinician.

In the intervention arm, 92.4% of patients successfully had their goals of care documented in the electronic health record within 6 months of randomization, compared with 17.6% of the usual care group (P less than .001). They also were more likely to have created an advanced directive (67.6% vs. 25.9%; P less than .001), Dr. Patel, of Stanford (Calif.) University, and her associates reported.

Patient satisfaction was also greater in the intervention arm, as measured by the Consumer Assessment of Health Care Providers & Systems “satisfaction with provider” item (mean score, 9.16 vs. 7.83; P less than .001). At 6 months, with respect to their oncology provider, patients in the intervention arm registered a mean increase in satisfaction score of 1.53 (P less than .001).

Patients who died were more likely to receive hospice care if they were in the LHW group (76.7% vs. 48.3%; P =.002). Those in the LHW group also had lower health care costs during the final 30 days of their lives ($1,048 vs. $23,482; P less than .001).

Overall, the study shows that LHWs may be one mechanism for delivering high-value care and avoiding unnecessary, burdensome late-life treatments, at least in cancer patients.

SOURCE: Patel MI et al. JAMA Oncol. 2018 Jul 26doi:10.1001/jamaoncol.2018.2446.

Lay health workers (LHWs) can improve documentation of cancer patients’ care preferences in the aftermath of their diagnosis, investigators report.

Physicians, palliative care workers, and other health professionals can help cancer patients understand their prognosis and establish end-of-life care preferences, but busy schedules and professional reluctance often prevent this. Nonclinical, nonprofessional LHWs often are employed to assist with screening and adherence, but little work has been done to use them in end-of-life care, Manali I. Patel, MD, MPH, and her associates wrote in JAMA Oncology.

To investigate their potential in this role, the researchers randomized 213 patients with stage 3 or 4 recurrent cancer to usual care or the LHW intervention, which included a 6-month structured program delivered by a single LHW who was enrolled in a part-time graduate health education program. The LHWs received an 80-hour online skills-based seminar and 4 weeks’ observation training with a palliative care team.

The LHWs helped patients with advanced care planning, including: education about goals of care, establishment of care preferences, establishment of a surrogate decision maker, creation of an advanced directive, and encouragement to discuss the patient’s care with the clinician.

In the intervention arm, 92.4% of patients successfully had their goals of care documented in the electronic health record within 6 months of randomization, compared with 17.6% of the usual care group (P less than .001). They also were more likely to have created an advanced directive (67.6% vs. 25.9%; P less than .001), Dr. Patel, of Stanford (Calif.) University, and her associates reported.

Patient satisfaction was also greater in the intervention arm, as measured by the Consumer Assessment of Health Care Providers & Systems “satisfaction with provider” item (mean score, 9.16 vs. 7.83; P less than .001). At 6 months, with respect to their oncology provider, patients in the intervention arm registered a mean increase in satisfaction score of 1.53 (P less than .001).

Patients who died were more likely to receive hospice care if they were in the LHW group (76.7% vs. 48.3%; P =.002). Those in the LHW group also had lower health care costs during the final 30 days of their lives ($1,048 vs. $23,482; P less than .001).

Overall, the study shows that LHWs may be one mechanism for delivering high-value care and avoiding unnecessary, burdensome late-life treatments, at least in cancer patients.

SOURCE: Patel MI et al. JAMA Oncol. 2018 Jul 26doi:10.1001/jamaoncol.2018.2446.

Lay health workers (LHWs) can improve documentation of cancer patients’ care preferences in the aftermath of their diagnosis, investigators report.

Physicians, palliative care workers, and other health professionals can help cancer patients understand their prognosis and establish end-of-life care preferences, but busy schedules and professional reluctance often prevent this. Nonclinical, nonprofessional LHWs often are employed to assist with screening and adherence, but little work has been done to use them in end-of-life care, Manali I. Patel, MD, MPH, and her associates wrote in JAMA Oncology.

To investigate their potential in this role, the researchers randomized 213 patients with stage 3 or 4 recurrent cancer to usual care or the LHW intervention, which included a 6-month structured program delivered by a single LHW who was enrolled in a part-time graduate health education program. The LHWs received an 80-hour online skills-based seminar and 4 weeks’ observation training with a palliative care team.

The LHWs helped patients with advanced care planning, including: education about goals of care, establishment of care preferences, establishment of a surrogate decision maker, creation of an advanced directive, and encouragement to discuss the patient’s care with the clinician.

In the intervention arm, 92.4% of patients successfully had their goals of care documented in the electronic health record within 6 months of randomization, compared with 17.6% of the usual care group (P less than .001). They also were more likely to have created an advanced directive (67.6% vs. 25.9%; P less than .001), Dr. Patel, of Stanford (Calif.) University, and her associates reported.

Patient satisfaction was also greater in the intervention arm, as measured by the Consumer Assessment of Health Care Providers & Systems “satisfaction with provider” item (mean score, 9.16 vs. 7.83; P less than .001). At 6 months, with respect to their oncology provider, patients in the intervention arm registered a mean increase in satisfaction score of 1.53 (P less than .001).

Patients who died were more likely to receive hospice care if they were in the LHW group (76.7% vs. 48.3%; P =.002). Those in the LHW group also had lower health care costs during the final 30 days of their lives ($1,048 vs. $23,482; P less than .001).

Overall, the study shows that LHWs may be one mechanism for delivering high-value care and avoiding unnecessary, burdensome late-life treatments, at least in cancer patients.

SOURCE: Patel MI et al. JAMA Oncol. 2018 Jul 26doi:10.1001/jamaoncol.2018.2446.

Every cancer diagnosis starts out as anything but. That’s what I was thinking when I met Sue Marcus (not her real name) in the emergency department one Friday afternoon.

“You know,” she said in a matter of fact manner. “I think I might have the flu.”

“Yes,” I said. “You might.”

“I was in Vegas a week ago, and the person next to me was sick.”

“It’s definitely possible. That’s one of the things we’ll test for.”

“I mean ... what else can it be?”

I had information Sue didn’t yet. All her blood counts were disturbingly low. On top of that, the lab had picked up several atypical appearing cells. They could be reactive, in the setting of infection, or they could be blasts – a new diagnosis of leukemia.

I paused.

“I’m going to say this now, so you know what we are looking for. There’s a lot more information we still need.”

“But?”

“But, another possibility is that it is cancer.”

“Cancer?”

“Leukemia, maybe.”

I explained the next steps. We would have flow cytometry by that night, but it’s not a perfect test. We were limited, actually, by logistics. It was a Friday night. We would do a bone marrow biopsy on Monday. It would be several days before we’d know with certainty.

That evening, the hematology fellow and I looked at the slide under the microscope. We agreed with the lab.

“That’s a blast, isn’t it?”

“Yes, I think it is.”

But they were not completely classic, and they were sporadic. It wasn’t enough to say for sure. Meanwhile, Sue, understandably, wanted answers.

“What did you see? Is it cancer, or not?”

There was flow cytometry that night, showing an abnormal population of cells. And then, finally, there was a bone marrow biopsy clinching the diagnosis.

We explained what the path ahead looked like: Hospitalization for a month. Chemotherapy, then a repeat bone marrow biopsy to look for response. Then more chemotherapy. Chances of remission. Long-term implications.

As we gathered more information, Sue’s questions evolved.

“Is it curable?”

“Can I go back to work?”

And one day, a week into treatment, she asked, “Am I going to die?”

Over my last 3 years as an internal medicine resident, I’ve been humbled by how often patients turned to me for answers to some of the most difficult questions I could imagine. Sometimes, the questions seemed purely factual, but often, they took a more existential bent: How should I spend my last months? What should I do now? Patients have asked me if they are going to die, along with when, how, and even why.

I’ve wrestled with how to communicate candidly, treading a delicate balance between being as up-front as possible while also recognizing the uncertainty inherent in predicting. I’ve struggled with walking the tightrope of delivering bad news while also emphasizing compassion and support.

I chose hematology and oncology in part because of the gravity of these interactions. I enjoy being a primary doctor for a complex, sick, patient population who are grappling with physically and emotionally challenging illness. I value longitudinal relationships with patients I know well. I found the medicine of hematology and oncology interdisciplinary, the details high stakes, and the big questions always at play. If it was meaningful work I sought, cancer became the ultimate question that mattered.

The changing landscape of cancer care is making these conversations substantially more difficult. A central tenet of medicine is truthfulness: setting the stage for what is going on and what to anticipate. It’s explaining the nuances of the upcoming treatment options, while also addressing what a person’s life may look like down the road. It’s understanding what matters most to a patient, understanding what therapeutic choices we can offer – and then trying to reconcile them, as best as we can.

This has always been hard. But it’s getting harder. The options we have to treat cancer are expanding rapidly as immunotherapy competes with the basics of chemotherapy, radiation, and surgery. We work alongside researchers looking to change the paradigm, collecting information on outcomes and side effects as we go along. We are learning and we are applying what we learn – in real time – on real people willing to try.

How can we speak honestly about a prognosis when our data are limited and our tools are in continuous flux? How can we prepare someone for what lies ahead when we are still trying to grasp what today looks like?

All the while, medical uncertainties are amplified by a complex system with many moving parts. It’s a system in which some patients cannot afford care, in which insurance companies may deny necessary treatment, and where families may come together or fall apart in the face of incredible adversity. There are factors outside the scope of pure medicine that make the path ahead all the hazier and navigating it all the more challenging.

In July, I began my hematology and oncology fellowship. I am caring for patients with a range of cancers, and all of that goes along with the weight of those diagnoses. Learning the most up-to-date management in a constantly evolving landscape will be an ongoing skill. That my patients allow me into their most vulnerable moments – and trust me with them – is a gift.

For patients like Sue, there sometimes remain more questions than answers. She recently underwent her third round of chemotherapy and endured multiple blood clots. With her insurance covering only limited interventions, she is deciding what to focus on and where to receive her care. Her story, like many others, continues to be written.

I am deeply aware of the difficulties that are a part of the world of cancer – and the heartbreak. How can we hold up scans triumphantly showing no recurrence in some patients while others suffer one failed treatment after another? When should we push for more therapy and when should we shift our efforts toward comfort? What should we prioritize – medically and personally – if time is limited?

These questions are hard, but I cannot think of any that are more meaningful.

This is a column about patients and uncertainty as I pursue my hematology and oncology fellowship and grapple with these questions. I look forward to sharing them with you each month.

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

Every cancer diagnosis starts out as anything but. That’s what I was thinking when I met Sue Marcus (not her real name) in the emergency department one Friday afternoon.

“You know,” she said in a matter of fact manner. “I think I might have the flu.”

“Yes,” I said. “You might.”

“I was in Vegas a week ago, and the person next to me was sick.”

“It’s definitely possible. That’s one of the things we’ll test for.”

“I mean ... what else can it be?”

I had information Sue didn’t yet. All her blood counts were disturbingly low. On top of that, the lab had picked up several atypical appearing cells. They could be reactive, in the setting of infection, or they could be blasts – a new diagnosis of leukemia.

I paused.

“I’m going to say this now, so you know what we are looking for. There’s a lot more information we still need.”

“But?”

“But, another possibility is that it is cancer.”

“Cancer?”

“Leukemia, maybe.”

I explained the next steps. We would have flow cytometry by that night, but it’s not a perfect test. We were limited, actually, by logistics. It was a Friday night. We would do a bone marrow biopsy on Monday. It would be several days before we’d know with certainty.

That evening, the hematology fellow and I looked at the slide under the microscope. We agreed with the lab.

“That’s a blast, isn’t it?”

“Yes, I think it is.”

But they were not completely classic, and they were sporadic. It wasn’t enough to say for sure. Meanwhile, Sue, understandably, wanted answers.

“What did you see? Is it cancer, or not?”

There was flow cytometry that night, showing an abnormal population of cells. And then, finally, there was a bone marrow biopsy clinching the diagnosis.

We explained what the path ahead looked like: Hospitalization for a month. Chemotherapy, then a repeat bone marrow biopsy to look for response. Then more chemotherapy. Chances of remission. Long-term implications.

As we gathered more information, Sue’s questions evolved.

“Is it curable?”

“Can I go back to work?”

And one day, a week into treatment, she asked, “Am I going to die?”

Over my last 3 years as an internal medicine resident, I’ve been humbled by how often patients turned to me for answers to some of the most difficult questions I could imagine. Sometimes, the questions seemed purely factual, but often, they took a more existential bent: How should I spend my last months? What should I do now? Patients have asked me if they are going to die, along with when, how, and even why.

I’ve wrestled with how to communicate candidly, treading a delicate balance between being as up-front as possible while also recognizing the uncertainty inherent in predicting. I’ve struggled with walking the tightrope of delivering bad news while also emphasizing compassion and support.

I chose hematology and oncology in part because of the gravity of these interactions. I enjoy being a primary doctor for a complex, sick, patient population who are grappling with physically and emotionally challenging illness. I value longitudinal relationships with patients I know well. I found the medicine of hematology and oncology interdisciplinary, the details high stakes, and the big questions always at play. If it was meaningful work I sought, cancer became the ultimate question that mattered.

The changing landscape of cancer care is making these conversations substantially more difficult. A central tenet of medicine is truthfulness: setting the stage for what is going on and what to anticipate. It’s explaining the nuances of the upcoming treatment options, while also addressing what a person’s life may look like down the road. It’s understanding what matters most to a patient, understanding what therapeutic choices we can offer – and then trying to reconcile them, as best as we can.

This has always been hard. But it’s getting harder. The options we have to treat cancer are expanding rapidly as immunotherapy competes with the basics of chemotherapy, radiation, and surgery. We work alongside researchers looking to change the paradigm, collecting information on outcomes and side effects as we go along. We are learning and we are applying what we learn – in real time – on real people willing to try.

How can we speak honestly about a prognosis when our data are limited and our tools are in continuous flux? How can we prepare someone for what lies ahead when we are still trying to grasp what today looks like?

All the while, medical uncertainties are amplified by a complex system with many moving parts. It’s a system in which some patients cannot afford care, in which insurance companies may deny necessary treatment, and where families may come together or fall apart in the face of incredible adversity. There are factors outside the scope of pure medicine that make the path ahead all the hazier and navigating it all the more challenging.

In July, I began my hematology and oncology fellowship. I am caring for patients with a range of cancers, and all of that goes along with the weight of those diagnoses. Learning the most up-to-date management in a constantly evolving landscape will be an ongoing skill. That my patients allow me into their most vulnerable moments – and trust me with them – is a gift.

For patients like Sue, there sometimes remain more questions than answers. She recently underwent her third round of chemotherapy and endured multiple blood clots. With her insurance covering only limited interventions, she is deciding what to focus on and where to receive her care. Her story, like many others, continues to be written.

I am deeply aware of the difficulties that are a part of the world of cancer – and the heartbreak. How can we hold up scans triumphantly showing no recurrence in some patients while others suffer one failed treatment after another? When should we push for more therapy and when should we shift our efforts toward comfort? What should we prioritize – medically and personally – if time is limited?

These questions are hard, but I cannot think of any that are more meaningful.

This is a column about patients and uncertainty as I pursue my hematology and oncology fellowship and grapple with these questions. I look forward to sharing them with you each month.

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

Every cancer diagnosis starts out as anything but. That’s what I was thinking when I met Sue Marcus (not her real name) in the emergency department one Friday afternoon.

“You know,” she said in a matter of fact manner. “I think I might have the flu.”

“Yes,” I said. “You might.”

“I was in Vegas a week ago, and the person next to me was sick.”

“It’s definitely possible. That’s one of the things we’ll test for.”

“I mean ... what else can it be?”

I had information Sue didn’t yet. All her blood counts were disturbingly low. On top of that, the lab had picked up several atypical appearing cells. They could be reactive, in the setting of infection, or they could be blasts – a new diagnosis of leukemia.

I paused.

“I’m going to say this now, so you know what we are looking for. There’s a lot more information we still need.”

“But?”

“But, another possibility is that it is cancer.”

“Cancer?”

“Leukemia, maybe.”

I explained the next steps. We would have flow cytometry by that night, but it’s not a perfect test. We were limited, actually, by logistics. It was a Friday night. We would do a bone marrow biopsy on Monday. It would be several days before we’d know with certainty.

That evening, the hematology fellow and I looked at the slide under the microscope. We agreed with the lab.

“That’s a blast, isn’t it?”

“Yes, I think it is.”

But they were not completely classic, and they were sporadic. It wasn’t enough to say for sure. Meanwhile, Sue, understandably, wanted answers.

“What did you see? Is it cancer, or not?”

There was flow cytometry that night, showing an abnormal population of cells. And then, finally, there was a bone marrow biopsy clinching the diagnosis.

We explained what the path ahead looked like: Hospitalization for a month. Chemotherapy, then a repeat bone marrow biopsy to look for response. Then more chemotherapy. Chances of remission. Long-term implications.

As we gathered more information, Sue’s questions evolved.

“Is it curable?”

“Can I go back to work?”

And one day, a week into treatment, she asked, “Am I going to die?”

Over my last 3 years as an internal medicine resident, I’ve been humbled by how often patients turned to me for answers to some of the most difficult questions I could imagine. Sometimes, the questions seemed purely factual, but often, they took a more existential bent: How should I spend my last months? What should I do now? Patients have asked me if they are going to die, along with when, how, and even why.

I’ve wrestled with how to communicate candidly, treading a delicate balance between being as up-front as possible while also recognizing the uncertainty inherent in predicting. I’ve struggled with walking the tightrope of delivering bad news while also emphasizing compassion and support.

I chose hematology and oncology in part because of the gravity of these interactions. I enjoy being a primary doctor for a complex, sick, patient population who are grappling with physically and emotionally challenging illness. I value longitudinal relationships with patients I know well. I found the medicine of hematology and oncology interdisciplinary, the details high stakes, and the big questions always at play. If it was meaningful work I sought, cancer became the ultimate question that mattered.

The changing landscape of cancer care is making these conversations substantially more difficult. A central tenet of medicine is truthfulness: setting the stage for what is going on and what to anticipate. It’s explaining the nuances of the upcoming treatment options, while also addressing what a person’s life may look like down the road. It’s understanding what matters most to a patient, understanding what therapeutic choices we can offer – and then trying to reconcile them, as best as we can.

This has always been hard. But it’s getting harder. The options we have to treat cancer are expanding rapidly as immunotherapy competes with the basics of chemotherapy, radiation, and surgery. We work alongside researchers looking to change the paradigm, collecting information on outcomes and side effects as we go along. We are learning and we are applying what we learn – in real time – on real people willing to try.

How can we speak honestly about a prognosis when our data are limited and our tools are in continuous flux? How can we prepare someone for what lies ahead when we are still trying to grasp what today looks like?

All the while, medical uncertainties are amplified by a complex system with many moving parts. It’s a system in which some patients cannot afford care, in which insurance companies may deny necessary treatment, and where families may come together or fall apart in the face of incredible adversity. There are factors outside the scope of pure medicine that make the path ahead all the hazier and navigating it all the more challenging.

In July, I began my hematology and oncology fellowship. I am caring for patients with a range of cancers, and all of that goes along with the weight of those diagnoses. Learning the most up-to-date management in a constantly evolving landscape will be an ongoing skill. That my patients allow me into their most vulnerable moments – and trust me with them – is a gift.

For patients like Sue, there sometimes remain more questions than answers. She recently underwent her third round of chemotherapy and endured multiple blood clots. With her insurance covering only limited interventions, she is deciding what to focus on and where to receive her care. Her story, like many others, continues to be written.

I am deeply aware of the difficulties that are a part of the world of cancer – and the heartbreak. How can we hold up scans triumphantly showing no recurrence in some patients while others suffer one failed treatment after another? When should we push for more therapy and when should we shift our efforts toward comfort? What should we prioritize – medically and personally – if time is limited?

These questions are hard, but I cannot think of any that are more meaningful.

This is a column about patients and uncertainty as I pursue my hematology and oncology fellowship and grapple with these questions. I look forward to sharing them with you each month.

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

For patients with non–small cell lung cancer (NSCLC), rapid EGFR-specific genotyping reduces time to initiation (TTI) of targeted therapy, compared with current next-generation sequencing (NGS) work flows, according to a recent study.

Rapid testing maintained concordance with NGS while cutting median turnaround time in half. In addition, an ultrarapid, next-day work flow allowed several highly symptomatic patients with NSCLC to start therapy within 1 week of biopsy, reported Ibiayi Dagogo-Jack, MD, of the Massachusetts General Hospital Waltham Cancer Center and her coauthors.

Molecular testing for patients with NSCLC is necessary to select appropriate therapies; however, “genotyping by NGS requires complex bioinformatics that can create treatment delays,” the investigators wrote in JCO Precision Oncology. “Some patients with NSCLC present with symptomatic disease that requires initiation of treatment before molecular testing results are available. To our knowledge, the impact of molecular testing turnaround time on clinical decision making has not been formally assessed in NSCLC.”

For rapid testing, biopsies were collected from 243 hospitalized patients with newly diagnosed, metastatic NSCLC and were then fixed in formalin. An EGFR-specific polymerase chain reaction assay was then used to identify exon 19 deletions and L858R mutations. The ultrarapid testing phase of the study involved eight highly symptomatic patients with newly diagnosed NSCLC. Biopsy samples in this group were frozen instead of fixed. Both the rapid and ultrarapid testing results were compared with 121 historical biopsies that had been genotyped by NGS.

The rapid testing’s work flow reduced TTI from 37 days to 22 days (P = .01) while maintaining high concordance with NGS (sensitivity, 98%; specificity, 100%). Median turnaround time dropped in half from 14 days to 7 days with rapid testing (P less than .001); ultrarapid testing had a turnaround time of approximately 1 day. The median TTI for the ultrarapid group was 9 days, and several patients were able to begin therapy within 1 week.

The investigators concluded that rapid and ultrarapid testing are a cost-effective, reliable means for decreasing turnaround time and TTI for patients with newly diagnosed, metastatic NSCLC. However, concurrent NGS genotyping should still be performed because NGS results may influence future therapy sequencing. With the ultrarapid work flow, additional sampling is recommended to offset the risk of tissue failure. The investigators noted that “the growing number of actionable targets substantiates the need for diagnostic strategies that expedite molecular analysis.”

The study was funded in part by the National Institutes of Health. Authors reported compensation from Merck, Boehringer Ingelheim, Takeda, and others.

SOURCE: Dagogo-Jack et al. JCO Precis Oncol. 2018 Jul 24. doi: 10.1200/PO.17.00299.

For patients with non–small cell lung cancer (NSCLC), rapid EGFR-specific genotyping reduces time to initiation (TTI) of targeted therapy, compared with current next-generation sequencing (NGS) work flows, according to a recent study.

Rapid testing maintained concordance with NGS while cutting median turnaround time in half. In addition, an ultrarapid, next-day work flow allowed several highly symptomatic patients with NSCLC to start therapy within 1 week of biopsy, reported Ibiayi Dagogo-Jack, MD, of the Massachusetts General Hospital Waltham Cancer Center and her coauthors.

Molecular testing for patients with NSCLC is necessary to select appropriate therapies; however, “genotyping by NGS requires complex bioinformatics that can create treatment delays,” the investigators wrote in JCO Precision Oncology. “Some patients with NSCLC present with symptomatic disease that requires initiation of treatment before molecular testing results are available. To our knowledge, the impact of molecular testing turnaround time on clinical decision making has not been formally assessed in NSCLC.”

For rapid testing, biopsies were collected from 243 hospitalized patients with newly diagnosed, metastatic NSCLC and were then fixed in formalin. An EGFR-specific polymerase chain reaction assay was then used to identify exon 19 deletions and L858R mutations. The ultrarapid testing phase of the study involved eight highly symptomatic patients with newly diagnosed NSCLC. Biopsy samples in this group were frozen instead of fixed. Both the rapid and ultrarapid testing results were compared with 121 historical biopsies that had been genotyped by NGS.

The rapid testing’s work flow reduced TTI from 37 days to 22 days (P = .01) while maintaining high concordance with NGS (sensitivity, 98%; specificity, 100%). Median turnaround time dropped in half from 14 days to 7 days with rapid testing (P less than .001); ultrarapid testing had a turnaround time of approximately 1 day. The median TTI for the ultrarapid group was 9 days, and several patients were able to begin therapy within 1 week.

The investigators concluded that rapid and ultrarapid testing are a cost-effective, reliable means for decreasing turnaround time and TTI for patients with newly diagnosed, metastatic NSCLC. However, concurrent NGS genotyping should still be performed because NGS results may influence future therapy sequencing. With the ultrarapid work flow, additional sampling is recommended to offset the risk of tissue failure. The investigators noted that “the growing number of actionable targets substantiates the need for diagnostic strategies that expedite molecular analysis.”

The study was funded in part by the National Institutes of Health. Authors reported compensation from Merck, Boehringer Ingelheim, Takeda, and others.

SOURCE: Dagogo-Jack et al. JCO Precis Oncol. 2018 Jul 24. doi: 10.1200/PO.17.00299.

For patients with non–small cell lung cancer (NSCLC), rapid EGFR-specific genotyping reduces time to initiation (TTI) of targeted therapy, compared with current next-generation sequencing (NGS) work flows, according to a recent study.

Rapid testing maintained concordance with NGS while cutting median turnaround time in half. In addition, an ultrarapid, next-day work flow allowed several highly symptomatic patients with NSCLC to start therapy within 1 week of biopsy, reported Ibiayi Dagogo-Jack, MD, of the Massachusetts General Hospital Waltham Cancer Center and her coauthors.

Molecular testing for patients with NSCLC is necessary to select appropriate therapies; however, “genotyping by NGS requires complex bioinformatics that can create treatment delays,” the investigators wrote in JCO Precision Oncology. “Some patients with NSCLC present with symptomatic disease that requires initiation of treatment before molecular testing results are available. To our knowledge, the impact of molecular testing turnaround time on clinical decision making has not been formally assessed in NSCLC.”

For rapid testing, biopsies were collected from 243 hospitalized patients with newly diagnosed, metastatic NSCLC and were then fixed in formalin. An EGFR-specific polymerase chain reaction assay was then used to identify exon 19 deletions and L858R mutations. The ultrarapid testing phase of the study involved eight highly symptomatic patients with newly diagnosed NSCLC. Biopsy samples in this group were frozen instead of fixed. Both the rapid and ultrarapid testing results were compared with 121 historical biopsies that had been genotyped by NGS.

The rapid testing’s work flow reduced TTI from 37 days to 22 days (P = .01) while maintaining high concordance with NGS (sensitivity, 98%; specificity, 100%). Median turnaround time dropped in half from 14 days to 7 days with rapid testing (P less than .001); ultrarapid testing had a turnaround time of approximately 1 day. The median TTI for the ultrarapid group was 9 days, and several patients were able to begin therapy within 1 week.

The investigators concluded that rapid and ultrarapid testing are a cost-effective, reliable means for decreasing turnaround time and TTI for patients with newly diagnosed, metastatic NSCLC. However, concurrent NGS genotyping should still be performed because NGS results may influence future therapy sequencing. With the ultrarapid work flow, additional sampling is recommended to offset the risk of tissue failure. The investigators noted that “the growing number of actionable targets substantiates the need for diagnostic strategies that expedite molecular analysis.”

The study was funded in part by the National Institutes of Health. Authors reported compensation from Merck, Boehringer Ingelheim, Takeda, and others.

SOURCE: Dagogo-Jack et al. JCO Precis Oncol. 2018 Jul 24. doi: 10.1200/PO.17.00299.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

A new index of frailty predicts survival in older patients with multiple myeloma based on accumulation of aging-associated deficits, rather than chronological age alone, investigators report. A 16% increased risk of death was seen for each 10% increase in the deficit-accumulation frailty index (DAFI), which includes 25 variables related health, function, and activities of daily living.

There was only a weak correlation between chronological age and increase in deficits tracked by the index, in contrast to a cohort without cancer, in which age and frailty were strongly correlated, the investigators reported in JCO Clinical Cancer Informatics.

“Our results demonstrate that, for patients with multiple myeloma, chronological age alone is not a good measure for assessing overall health,” study author Tanya M. Wildes, MD, of Washington University, St. Louis, said in a news release from the American Society of Clinical Oncology.

Existing tools to assess frailty include an index proposed by the International Myeloma Working Group that looks at age plus other indexes related to comorbidities and activities of daily living, and the revised Myeloma Comorbidity Index that incorporates age with other prognostic factors.

“Although both tools provide prognostic information, chronological age automatically increases frailty without taking biologic or functional age into account,” Dr. Wildes and her coauthors wrote in their report.

By contrast, the DAFI is based on the concept of biologic age, in which the health status of an individual is measured based on the proportion of aging-associated deficits they have accumulated, according to the authors.

To create the DAFI, Dr. Wildes and her colleagues analyzed nearly 2.7 million records of noncancer patients aged 66 years or older in the SEER Medicare Health Outcomes Survey (MHOS) database. They identified 25 variables in the database representing chronic health conditions, activities of daily living, functioning, mental health, and general health.

An individual’s DAFI score was calculated as the sum of scores for each of the 25 variables as 0 for absent, 0.5 for limited, and 1 for present. Predicted DAFI means were calculated for each year of age and used to create age-specific cut points to determine whether an individual would be considered frail or not versus others of the same age.

“In other words, the same frailty score may qualify an 80-year-old individual as fit and a 70-year-old as frail, depending on the cutoff for their respective age group,” investigators explained in their report.

They applied the index to 305 patients with newly diagnosed myeloma in the SEER-MHOS database who were 66 years of age or older (median age, 76 years) and had completed the survey within 1 year of diagnosis.

The DAFI classified 52% of the myeloma patients as frail, and for that group, median overall survival was 26.8 months, versus 43.7 months for nonfrail patients (P = .015), according to the reported data. For each 10% increase in score, the risk of death increased by 16% (P less than .001).

Notably, advancing age was very weakly correlated with increased age-related deficits in the myeloma cohort (r2 = 0.15; P = .010), according to investigators, but very strongly correlated with deficits in the cohort of noncancer patients (r2 = 0.98; P less than .001).

“This suggests that, in patients with multiple myeloma, the prevalence of impairments across domains of function, chronic comorbidities, general health, and mental health are more related to the overall burden of myeloma rather than chronological age alone,” the investigators wrote.

The information used to calculate a DAFI score is easily obtainable during a clinic visit, according to the authors, who provided an overview of all 25 variables in the journal article.

Further development of a computerized program would further enhance usability in the clinic, allowing for real-time calculation during a patient visit, they said.

Survivorship expert Merry Jennifer Markham, MD, said in the ASCO news release that this frailty index is notable because it accounts for more than just chronological age. “Knowing this information can help oncologists have more informed discussions with patients about their prognosis, which in turn can empower patients and families as they weigh treatment options,” she said.

The research was supported by National Cancer Institute. Dr. Wildes reported honoraria from Carevive Systems and research funding from Janssen Oncology. Another coauthor reported honoraria from Celgene and Janssen, and a consulting or advisory role with Amgen and Takeda.

 

SOURCE: Mian HS et al. JCO Clin Cancer Inform. 2018 Jul 25. 2018 Jul 25. doi: 10.1200/CCI.18.00043.

Picture this: Creating visual representations of symptom clusters may help oncologists identify and treat sentinel symptoms in patients who are receiving cancer therapies and potentially avoid costly and unnecessary acute hospitalizations.

Network visualizations – graphic representations of the frequency of individual symptoms and the strength of their co-occurrence with other symptoms – could be used by clinicians in urgent-care settings to determine whether a presenting symptom or cluster of symptoms could be safely managed in the outpatient setting or requires hospitalization, according to Bobby Daly, MD, and his colleagues at Memorial Sloan Kettering Cancer Center in New York.

“Uncontrolled symptoms are associated with unplanned acute care. Recognition of the complexity of symptom co-occurrence can drive improved management strategies,” the investigators wrote. The report was published in the Journal of Oncology Practice.

Preventing hospitalizations related to treatment toxicities is both sound clinical and financial practice.

“Patients who receive chemotherapy have, on average, one hospital admission and two emergency department visits per year, and 40%-50% of these stem from symptoms related to their treatment. Acute hospitalizations account for 48% of total cancer expenditures. Considerable regional variation exists, which suggests that these hospitalizations may be avoidable,” they wrote.

The Centers for Medicare & Medicaid Services has identified 10 potentially preventable conditions that may result in hospitalizations, and plans to measure the performance of cancer centers based on the frequency of urgent care visits and admissions for each condition.

The conditions (in alphabetical order) are: anemia, dehydration, diarrhea, emesis, fever, nausea, neutropenia, pain, pneumonia, and sepsis.

To get a better handle on symptom clusters in patients undergoing active cancer therapy, the investigators used an analytical method involving creation of network visualizations of symptom clusters.

“It has been established that physicians are uncomfortable with managing symptom clusters, and by better elucidating these clusters, we can improve management strategies,” Dr. Daly and his associates wrote.

They identified 23,341 unique patient visits to their center’s urgent care department in 2016, and included in their analysis only those patients who had received an intravenous chemotherapy agent, oral antineoplastic therapy, or immunotherapy within 30 days of presentation. They drew on the electronic health record (EHR) for information about the chief complaint and primary diagnosis for each visit.

They then created three patient cohorts for identifying and mapping potentially preventable symptom clusters.

Cohort 1 comprised patients who were receiving active treatment and presented to the urgent care center with one of the CMS-defined symptoms.

Cohort 2 comprised patients who were receiving active treatment and were evaluated with a clinician-developed definition of a potentially preventable symptom, defined as “a symptom that could be managed safely in the outpatient setting if the clinical team identified said symptom early and managed it proactively.”

Cohort 3 was similar to cohort 2, but included only those patients who started treatment for the first time.

The authors identified 6,429 presentations in cohort 1, and in this group of patients the network analysis identified two distinct symptom clusters centered around pain and fever.

In cohort 2, there were 5,731 visits and six symptom clusters centered around fever, nausea/emesis, fatigue, deep vein thrombosis, pain, and ascites.

In cohort 3, there were 1,154 visits and four symptom clusters centered around fever, nausea/emesis, fatigue, and deep vein thrombosis.

“By using EHR data fields for [urgent care center] primary diagnoses and chief complaints, we elicited symptom information and linked it to unplanned acute care. Unplanned acute care is of increasing importance to patients because it disrupts patients’ treatment trajectories as well as their lives outside the clinic. Use of the EHR also allowed for granular symptom data, such as a particular site of pain rather than just pain itself, which is absent from traditional sources of patient-reported symptom assessments,” Dr. Daly and his colleagues said.

The investigators recommend using data from the EHR in combination with “big data” artificial intelligence techniques to allow early detection of patients at risk for symptom clusters.

The study was supported by an ASCO Health Policy Fellowship to Dr. Daly. He disclosed employment and stock ownership with Quadrant Holdings Corporation, and stock ownership in CVS Health, Johnson & Johnson, McKesson, Lilly and the Walgreens Boots Alliance.

SOURCE: Daly B et al. J Oncol Practice, 2018 Jul 17. doi: 10.1200/JOP.18.00199.

Picture this: Creating visual representations of symptom clusters may help oncologists identify and treat sentinel symptoms in patients who are receiving cancer therapies and potentially avoid costly and unnecessary acute hospitalizations.

Network visualizations – graphic representations of the frequency of individual symptoms and the strength of their co-occurrence with other symptoms – could be used by clinicians in urgent-care settings to determine whether a presenting symptom or cluster of symptoms could be safely managed in the outpatient setting or requires hospitalization, according to Bobby Daly, MD, and his colleagues at Memorial Sloan Kettering Cancer Center in New York.

“Uncontrolled symptoms are associated with unplanned acute care. Recognition of the complexity of symptom co-occurrence can drive improved management strategies,” the investigators wrote. The report was published in the Journal of Oncology Practice.

Preventing hospitalizations related to treatment toxicities is both sound clinical and financial practice.

“Patients who receive chemotherapy have, on average, one hospital admission and two emergency department visits per year, and 40%-50% of these stem from symptoms related to their treatment. Acute hospitalizations account for 48% of total cancer expenditures. Considerable regional variation exists, which suggests that these hospitalizations may be avoidable,” they wrote.

The Centers for Medicare & Medicaid Services has identified 10 potentially preventable conditions that may result in hospitalizations, and plans to measure the performance of cancer centers based on the frequency of urgent care visits and admissions for each condition.

The conditions (in alphabetical order) are: anemia, dehydration, diarrhea, emesis, fever, nausea, neutropenia, pain, pneumonia, and sepsis.

To get a better handle on symptom clusters in patients undergoing active cancer therapy, the investigators used an analytical method involving creation of network visualizations of symptom clusters.

“It has been established that physicians are uncomfortable with managing symptom clusters, and by better elucidating these clusters, we can improve management strategies,” Dr. Daly and his associates wrote.

They identified 23,341 unique patient visits to their center’s urgent care department in 2016, and included in their analysis only those patients who had received an intravenous chemotherapy agent, oral antineoplastic therapy, or immunotherapy within 30 days of presentation. They drew on the electronic health record (EHR) for information about the chief complaint and primary diagnosis for each visit.

They then created three patient cohorts for identifying and mapping potentially preventable symptom clusters.

Cohort 1 comprised patients who were receiving active treatment and presented to the urgent care center with one of the CMS-defined symptoms.

Cohort 2 comprised patients who were receiving active treatment and were evaluated with a clinician-developed definition of a potentially preventable symptom, defined as “a symptom that could be managed safely in the outpatient setting if the clinical team identified said symptom early and managed it proactively.”

Cohort 3 was similar to cohort 2, but included only those patients who started treatment for the first time.

The authors identified 6,429 presentations in cohort 1, and in this group of patients the network analysis identified two distinct symptom clusters centered around pain and fever.

In cohort 2, there were 5,731 visits and six symptom clusters centered around fever, nausea/emesis, fatigue, deep vein thrombosis, pain, and ascites.

In cohort 3, there were 1,154 visits and four symptom clusters centered around fever, nausea/emesis, fatigue, and deep vein thrombosis.

“By using EHR data fields for [urgent care center] primary diagnoses and chief complaints, we elicited symptom information and linked it to unplanned acute care. Unplanned acute care is of increasing importance to patients because it disrupts patients’ treatment trajectories as well as their lives outside the clinic. Use of the EHR also allowed for granular symptom data, such as a particular site of pain rather than just pain itself, which is absent from traditional sources of patient-reported symptom assessments,” Dr. Daly and his colleagues said.

The investigators recommend using data from the EHR in combination with “big data” artificial intelligence techniques to allow early detection of patients at risk for symptom clusters.

The study was supported by an ASCO Health Policy Fellowship to Dr. Daly. He disclosed employment and stock ownership with Quadrant Holdings Corporation, and stock ownership in CVS Health, Johnson & Johnson, McKesson, Lilly and the Walgreens Boots Alliance.

SOURCE: Daly B et al. J Oncol Practice, 2018 Jul 17. doi: 10.1200/JOP.18.00199.

Picture this: Creating visual representations of symptom clusters may help oncologists identify and treat sentinel symptoms in patients who are receiving cancer therapies and potentially avoid costly and unnecessary acute hospitalizations.

Network visualizations – graphic representations of the frequency of individual symptoms and the strength of their co-occurrence with other symptoms – could be used by clinicians in urgent-care settings to determine whether a presenting symptom or cluster of symptoms could be safely managed in the outpatient setting or requires hospitalization, according to Bobby Daly, MD, and his colleagues at Memorial Sloan Kettering Cancer Center in New York.

“Uncontrolled symptoms are associated with unplanned acute care. Recognition of the complexity of symptom co-occurrence can drive improved management strategies,” the investigators wrote. The report was published in the Journal of Oncology Practice.

Preventing hospitalizations related to treatment toxicities is both sound clinical and financial practice.

“Patients who receive chemotherapy have, on average, one hospital admission and two emergency department visits per year, and 40%-50% of these stem from symptoms related to their treatment. Acute hospitalizations account for 48% of total cancer expenditures. Considerable regional variation exists, which suggests that these hospitalizations may be avoidable,” they wrote.

The Centers for Medicare & Medicaid Services has identified 10 potentially preventable conditions that may result in hospitalizations, and plans to measure the performance of cancer centers based on the frequency of urgent care visits and admissions for each condition.

The conditions (in alphabetical order) are: anemia, dehydration, diarrhea, emesis, fever, nausea, neutropenia, pain, pneumonia, and sepsis.

To get a better handle on symptom clusters in patients undergoing active cancer therapy, the investigators used an analytical method involving creation of network visualizations of symptom clusters.

“It has been established that physicians are uncomfortable with managing symptom clusters, and by better elucidating these clusters, we can improve management strategies,” Dr. Daly and his associates wrote.

They identified 23,341 unique patient visits to their center’s urgent care department in 2016, and included in their analysis only those patients who had received an intravenous chemotherapy agent, oral antineoplastic therapy, or immunotherapy within 30 days of presentation. They drew on the electronic health record (EHR) for information about the chief complaint and primary diagnosis for each visit.

They then created three patient cohorts for identifying and mapping potentially preventable symptom clusters.

Cohort 1 comprised patients who were receiving active treatment and presented to the urgent care center with one of the CMS-defined symptoms.

Cohort 2 comprised patients who were receiving active treatment and were evaluated with a clinician-developed definition of a potentially preventable symptom, defined as “a symptom that could be managed safely in the outpatient setting if the clinical team identified said symptom early and managed it proactively.”

Cohort 3 was similar to cohort 2, but included only those patients who started treatment for the first time.

The authors identified 6,429 presentations in cohort 1, and in this group of patients the network analysis identified two distinct symptom clusters centered around pain and fever.

In cohort 2, there were 5,731 visits and six symptom clusters centered around fever, nausea/emesis, fatigue, deep vein thrombosis, pain, and ascites.

In cohort 3, there were 1,154 visits and four symptom clusters centered around fever, nausea/emesis, fatigue, and deep vein thrombosis.

“By using EHR data fields for [urgent care center] primary diagnoses and chief complaints, we elicited symptom information and linked it to unplanned acute care. Unplanned acute care is of increasing importance to patients because it disrupts patients’ treatment trajectories as well as their lives outside the clinic. Use of the EHR also allowed for granular symptom data, such as a particular site of pain rather than just pain itself, which is absent from traditional sources of patient-reported symptom assessments,” Dr. Daly and his colleagues said.

The investigators recommend using data from the EHR in combination with “big data” artificial intelligence techniques to allow early detection of patients at risk for symptom clusters.

The study was supported by an ASCO Health Policy Fellowship to Dr. Daly. He disclosed employment and stock ownership with Quadrant Holdings Corporation, and stock ownership in CVS Health, Johnson & Johnson, McKesson, Lilly and the Walgreens Boots Alliance.

SOURCE: Daly B et al. J Oncol Practice, 2018 Jul 17. doi: 10.1200/JOP.18.00199.

Nivestym (filgrastim-aafi), a biosimilar to Neupogen (filgrastim) was approved July 20 by the Food and Drug Administration, according to a statement provided by the agency. Nivestym is the second biosimilar to Neupogen to be approved in the United States.

• Patients with cancer receiving myelosuppressive chemotherapy.
• Patients with acute myeloid leukemia receiving induction or consolidation chemotherapy.
• Patients with cancer undergoing bone marrow transplantation.
• Patients undergoing autologous peripheral blood progenitor cell collection and therapy.
• Patients with severe chronic neutropenia.

According to a press release from Pfizer, the manufacturer of the biosimilar, Nivestym is expected to be available in the United States at a significant discount to the current wholesale acquisition cost of Neupogen, which is not inclusive of discounts to payers, providers, distributors, and other purchasing organizations.

The FDA statement notes that a biosimilar is approved based on a showing that it is highly similar to an already approved biologic product, known as a reference product. The biosimilar also must be shown to have no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products.

Prescribing information is available here.

[email protected]

Nivestym (filgrastim-aafi), a biosimilar to Neupogen (filgrastim) was approved July 20 by the Food and Drug Administration, according to a statement provided by the agency. Nivestym is the second biosimilar to Neupogen to be approved in the United States.

• Patients with cancer receiving myelosuppressive chemotherapy.
• Patients with acute myeloid leukemia receiving induction or consolidation chemotherapy.
• Patients with cancer undergoing bone marrow transplantation.
• Patients undergoing autologous peripheral blood progenitor cell collection and therapy.
• Patients with severe chronic neutropenia.

According to a press release from Pfizer, the manufacturer of the biosimilar, Nivestym is expected to be available in the United States at a significant discount to the current wholesale acquisition cost of Neupogen, which is not inclusive of discounts to payers, providers, distributors, and other purchasing organizations.

The FDA statement notes that a biosimilar is approved based on a showing that it is highly similar to an already approved biologic product, known as a reference product. The biosimilar also must be shown to have no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products.

Prescribing information is available here.

[email protected]

Nivestym (filgrastim-aafi), a biosimilar to Neupogen (filgrastim) was approved July 20 by the Food and Drug Administration, according to a statement provided by the agency. Nivestym is the second biosimilar to Neupogen to be approved in the United States.

• Patients with cancer receiving myelosuppressive chemotherapy.
• Patients with acute myeloid leukemia receiving induction or consolidation chemotherapy.
• Patients with cancer undergoing bone marrow transplantation.
• Patients undergoing autologous peripheral blood progenitor cell collection and therapy.
• Patients with severe chronic neutropenia.

According to a press release from Pfizer, the manufacturer of the biosimilar, Nivestym is expected to be available in the United States at a significant discount to the current wholesale acquisition cost of Neupogen, which is not inclusive of discounts to payers, providers, distributors, and other purchasing organizations.

The FDA statement notes that a biosimilar is approved based on a showing that it is highly similar to an already approved biologic product, known as a reference product. The biosimilar also must be shown to have no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products.

Prescribing information is available here.

[email protected]

Women with platinum-sensitive recurrent ovarian cancer who received maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor had no significant decreases in health-related quality of life, outcomes data from two randomized clinical trials show.

Health-related quality of life (HRQOL) analyses from the SOLO2/ENGOT-Ov-21 trial comparing olaparib (Lynparza) with placebo and the ENGOT-OV16/NOVA trial comparing niraparib (Zejula) with placebo as maintenance therapy in women with ongoing responses to their last platinum-based chemotherapy showed that neither agent had major detrimental effects on patient-reported outcomes, further supporting the progression-free survival benefits previously seen with each agent in its respective trials.

“These results show the significant benefit of maintenance olaparib to patients beyond the RECIST [Response Evaluation Criteria in Solid Tumors] definition of progression, the primary endpoint of SOLO2, and highlight the importance of including patient-centered outcomes in addition to HRQOL in trials of maintenance therapy, in line with the recommendations of the 5th Ovarian Cancer Consensus Conference,” wrote Michael Friedlander, MD, of the University of New South Wales Clinical School and Prince of Wales Hospital in Randwick, New South Wales, Australia, and his colleagues.

Similarly, Amit M. Oza, MD, of Princess Margaret Cancer Centre in Toronto, and his coinvestigators in the ENGOT-OV16/NOVA trial found that “niraparib has no significant negative effect on QOL in patients with recurrent ovarian cancer. Combined with the evidence of increased progression-free survival with niraparib in the maintenance setting, these findings support the addition of niraparib as a component of standard of care.”

Both studies were published online in The Lancet Oncology: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7, and Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

SOLO2 QOL summary

In SOLO2, patients with a germline BRCA1 or BRCA2 mutation and platinum-sensitive ovarian cancer that relapsed after at least two lines of chemotherapy were randomly assigned to receive either oral olaparib 300 mg twice daily (196 patients) or placebo (99 patients).

The prespecified primary HRQOL analysis looked at the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer (FACT-O) Trial Outcome Index (TOI) score during the first 12 months of the study.

In addition, the investigators examined secondary planned QOL analyses, including duration of good quality of life, defined as time without significant symptoms of toxicity, or TWiST, and quality-adjusted progression-free survival (QAPFS).

The adjusted average mean change from baseline over the first 12 months in TOI was –2.90 with olaparib vs. –2.87 with placebo (nonsignificant).

In contrast, patients treated with olaparib had significantly better mean QAPFS (13.96 vs. 7.28 months) and TWiST (15.03 vs. 7.70 months) results.

“All these predefined endpoints support the benefit to patients of a prolongation of progression-free survival, which is the primary endpoint in maintenance trials in ovarian cancer, and should be routinely included in future trials,” wrote Dr. Friedlander and his associates.
 

ENGOT-OV16/NOVA QOL summary

Investigators for this trial enrolled patients into two independent cohorts based on germline BRCA mutations or lack thereof. In all, 138 patients were assigned to niraparib and 65 to placebo in the germline BRCA mutation cohort, and 234 to niraparib and 116 to placebo in the nonmutation cohort.

The current study assessed patient-reported outcomes in the intention-to-treat population using different validated instruments from those assessed in SOLO2: the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI) and European QOL five-dimension five-level questionnaire (EQ-5D-5L).

The outcomes were reported every 8 weeks for the first 14 treatment cycles and every 12 weeks thereafter.

The investigators looked at the effects of hematologic toxicities on QOL with disutility analyses (measuring the decrement on QOL of a particular symptom or complication) of the most common grade 3-4 adverse events (thrombocytopenia, anemia, and neutropenia) using a mixed model with covariates.

They found that overall QOL scores remained stable during treatment and the preprogression period among patients on niraparib in each cohort, and that there were no significant differences in preprogression EQ-5D-5L scores between niraparib- or placebo-treated patients in either cohort.

In addition, patient-reported lack of energy and pain, two of the most common baseline symptoms, either remained stable or improved during maintenance, although the proportion of patients reporting nausea increased at cycle 2. The incidence of nausea declined over subsequent cycles, and eventually approached baseline levels, the investigators said.

Hematologic toxicities were the most common grade 3 or 4 adverse events seen in patients treated with niraparib, including thrombocytopenia in 34%, anemia in 25%, and neutropenia in 20%. However, disutility analyses showed no significant effects of these toxicities on QOL measures.

“This analysis did not examine integrated measures of duration and QOL such as time without symptoms and toxicity or quality-adjusted progression-free survival. Although these analyses were beyond the scope of this report, these measures are potentially of interest and we plan to assess these as part of future research,” wrote Dr. Oza and his associates.

SOURCE: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7. Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

Women with platinum-sensitive recurrent ovarian cancer who received maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor had no significant decreases in health-related quality of life, outcomes data from two randomized clinical trials show.

Health-related quality of life (HRQOL) analyses from the SOLO2/ENGOT-Ov-21 trial comparing olaparib (Lynparza) with placebo and the ENGOT-OV16/NOVA trial comparing niraparib (Zejula) with placebo as maintenance therapy in women with ongoing responses to their last platinum-based chemotherapy showed that neither agent had major detrimental effects on patient-reported outcomes, further supporting the progression-free survival benefits previously seen with each agent in its respective trials.

“These results show the significant benefit of maintenance olaparib to patients beyond the RECIST [Response Evaluation Criteria in Solid Tumors] definition of progression, the primary endpoint of SOLO2, and highlight the importance of including patient-centered outcomes in addition to HRQOL in trials of maintenance therapy, in line with the recommendations of the 5th Ovarian Cancer Consensus Conference,” wrote Michael Friedlander, MD, of the University of New South Wales Clinical School and Prince of Wales Hospital in Randwick, New South Wales, Australia, and his colleagues.

Similarly, Amit M. Oza, MD, of Princess Margaret Cancer Centre in Toronto, and his coinvestigators in the ENGOT-OV16/NOVA trial found that “niraparib has no significant negative effect on QOL in patients with recurrent ovarian cancer. Combined with the evidence of increased progression-free survival with niraparib in the maintenance setting, these findings support the addition of niraparib as a component of standard of care.”

Both studies were published online in The Lancet Oncology: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7, and Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

SOLO2 QOL summary

In SOLO2, patients with a germline BRCA1 or BRCA2 mutation and platinum-sensitive ovarian cancer that relapsed after at least two lines of chemotherapy were randomly assigned to receive either oral olaparib 300 mg twice daily (196 patients) or placebo (99 patients).

The prespecified primary HRQOL analysis looked at the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer (FACT-O) Trial Outcome Index (TOI) score during the first 12 months of the study.

In addition, the investigators examined secondary planned QOL analyses, including duration of good quality of life, defined as time without significant symptoms of toxicity, or TWiST, and quality-adjusted progression-free survival (QAPFS).

The adjusted average mean change from baseline over the first 12 months in TOI was –2.90 with olaparib vs. –2.87 with placebo (nonsignificant).

In contrast, patients treated with olaparib had significantly better mean QAPFS (13.96 vs. 7.28 months) and TWiST (15.03 vs. 7.70 months) results.

“All these predefined endpoints support the benefit to patients of a prolongation of progression-free survival, which is the primary endpoint in maintenance trials in ovarian cancer, and should be routinely included in future trials,” wrote Dr. Friedlander and his associates.
 

ENGOT-OV16/NOVA QOL summary

Investigators for this trial enrolled patients into two independent cohorts based on germline BRCA mutations or lack thereof. In all, 138 patients were assigned to niraparib and 65 to placebo in the germline BRCA mutation cohort, and 234 to niraparib and 116 to placebo in the nonmutation cohort.

The current study assessed patient-reported outcomes in the intention-to-treat population using different validated instruments from those assessed in SOLO2: the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI) and European QOL five-dimension five-level questionnaire (EQ-5D-5L).

The outcomes were reported every 8 weeks for the first 14 treatment cycles and every 12 weeks thereafter.

The investigators looked at the effects of hematologic toxicities on QOL with disutility analyses (measuring the decrement on QOL of a particular symptom or complication) of the most common grade 3-4 adverse events (thrombocytopenia, anemia, and neutropenia) using a mixed model with covariates.

They found that overall QOL scores remained stable during treatment and the preprogression period among patients on niraparib in each cohort, and that there were no significant differences in preprogression EQ-5D-5L scores between niraparib- or placebo-treated patients in either cohort.

In addition, patient-reported lack of energy and pain, two of the most common baseline symptoms, either remained stable or improved during maintenance, although the proportion of patients reporting nausea increased at cycle 2. The incidence of nausea declined over subsequent cycles, and eventually approached baseline levels, the investigators said.

Hematologic toxicities were the most common grade 3 or 4 adverse events seen in patients treated with niraparib, including thrombocytopenia in 34%, anemia in 25%, and neutropenia in 20%. However, disutility analyses showed no significant effects of these toxicities on QOL measures.

“This analysis did not examine integrated measures of duration and QOL such as time without symptoms and toxicity or quality-adjusted progression-free survival. Although these analyses were beyond the scope of this report, these measures are potentially of interest and we plan to assess these as part of future research,” wrote Dr. Oza and his associates.

SOURCE: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7. Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

Women with platinum-sensitive recurrent ovarian cancer who received maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor had no significant decreases in health-related quality of life, outcomes data from two randomized clinical trials show.

Health-related quality of life (HRQOL) analyses from the SOLO2/ENGOT-Ov-21 trial comparing olaparib (Lynparza) with placebo and the ENGOT-OV16/NOVA trial comparing niraparib (Zejula) with placebo as maintenance therapy in women with ongoing responses to their last platinum-based chemotherapy showed that neither agent had major detrimental effects on patient-reported outcomes, further supporting the progression-free survival benefits previously seen with each agent in its respective trials.

“These results show the significant benefit of maintenance olaparib to patients beyond the RECIST [Response Evaluation Criteria in Solid Tumors] definition of progression, the primary endpoint of SOLO2, and highlight the importance of including patient-centered outcomes in addition to HRQOL in trials of maintenance therapy, in line with the recommendations of the 5th Ovarian Cancer Consensus Conference,” wrote Michael Friedlander, MD, of the University of New South Wales Clinical School and Prince of Wales Hospital in Randwick, New South Wales, Australia, and his colleagues.

Similarly, Amit M. Oza, MD, of Princess Margaret Cancer Centre in Toronto, and his coinvestigators in the ENGOT-OV16/NOVA trial found that “niraparib has no significant negative effect on QOL in patients with recurrent ovarian cancer. Combined with the evidence of increased progression-free survival with niraparib in the maintenance setting, these findings support the addition of niraparib as a component of standard of care.”

Both studies were published online in The Lancet Oncology: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7, and Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

SOLO2 QOL summary

In SOLO2, patients with a germline BRCA1 or BRCA2 mutation and platinum-sensitive ovarian cancer that relapsed after at least two lines of chemotherapy were randomly assigned to receive either oral olaparib 300 mg twice daily (196 patients) or placebo (99 patients).

The prespecified primary HRQOL analysis looked at the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer (FACT-O) Trial Outcome Index (TOI) score during the first 12 months of the study.

In addition, the investigators examined secondary planned QOL analyses, including duration of good quality of life, defined as time without significant symptoms of toxicity, or TWiST, and quality-adjusted progression-free survival (QAPFS).

The adjusted average mean change from baseline over the first 12 months in TOI was –2.90 with olaparib vs. –2.87 with placebo (nonsignificant).

In contrast, patients treated with olaparib had significantly better mean QAPFS (13.96 vs. 7.28 months) and TWiST (15.03 vs. 7.70 months) results.

“All these predefined endpoints support the benefit to patients of a prolongation of progression-free survival, which is the primary endpoint in maintenance trials in ovarian cancer, and should be routinely included in future trials,” wrote Dr. Friedlander and his associates.
 

ENGOT-OV16/NOVA QOL summary

Investigators for this trial enrolled patients into two independent cohorts based on germline BRCA mutations or lack thereof. In all, 138 patients were assigned to niraparib and 65 to placebo in the germline BRCA mutation cohort, and 234 to niraparib and 116 to placebo in the nonmutation cohort.

The current study assessed patient-reported outcomes in the intention-to-treat population using different validated instruments from those assessed in SOLO2: the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI) and European QOL five-dimension five-level questionnaire (EQ-5D-5L).

The outcomes were reported every 8 weeks for the first 14 treatment cycles and every 12 weeks thereafter.

The investigators looked at the effects of hematologic toxicities on QOL with disutility analyses (measuring the decrement on QOL of a particular symptom or complication) of the most common grade 3-4 adverse events (thrombocytopenia, anemia, and neutropenia) using a mixed model with covariates.

They found that overall QOL scores remained stable during treatment and the preprogression period among patients on niraparib in each cohort, and that there were no significant differences in preprogression EQ-5D-5L scores between niraparib- or placebo-treated patients in either cohort.

In addition, patient-reported lack of energy and pain, two of the most common baseline symptoms, either remained stable or improved during maintenance, although the proportion of patients reporting nausea increased at cycle 2. The incidence of nausea declined over subsequent cycles, and eventually approached baseline levels, the investigators said.

Hematologic toxicities were the most common grade 3 or 4 adverse events seen in patients treated with niraparib, including thrombocytopenia in 34%, anemia in 25%, and neutropenia in 20%. However, disutility analyses showed no significant effects of these toxicities on QOL measures.

“This analysis did not examine integrated measures of duration and QOL such as time without symptoms and toxicity or quality-adjusted progression-free survival. Although these analyses were beyond the scope of this report, these measures are potentially of interest and we plan to assess these as part of future research,” wrote Dr. Oza and his associates.

SOURCE: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7. Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

Melanoma patients who took high doses of glucocorticoids for hypophysitis induced by the checkpoint-inhibitor ipilimumab had a lower overall survival time and a shorter time to treatment failure than did patients taking low-dose steroids for the adverse event, according to a new retrospective analysis in Cancer.

“Treatment with high-dose glucocorticoids does not appear to confer any obvious advantage to patients with IH (ipilimumab-induced hypophysitis) and may negatively affect tumor response to CPI (checkpoint-inhibitor therapy),” wrote Alexander Faje, MD, a neuroendocrinologist at Massachusetts General Hospital, Boston. “We recommend against the routine use of higher doses in these patients and that such treatment should be reserved for clinical indications like visual compromise or perhaps for intractable headache.”

Hypophysitis after treatment with a CTLA-4 inhibitor, such as ipilimumab, can approach 12%, though it is much less common with the checkpoint inhibitors that target PD-1 and PD-L1. Past studies examining the effects of glucocorticoids for immune-related adverse events have compared patients with severe events to those with minimal or no events. Since emergence of hypophysitis correlates with better overall survival, this is a flawed approach, the researchers said.

For their study, the researchers compared groups of patients with the same immune-related adverse events who received treatment with varying amounts of glucocorticoids.

They reviewed outcomes for 64 melanoma patients who had received ipilimumab monotherapy and were diagnosed with ipilimumab-induced hypophysitis treated in the Partners Healthcare system. Fourteen patients had received low-dose glucocorticoids, defined as a maximum average daily dose of 7.5 mg of prednisone or the equivalent. Fifty patients received high-dose glucocorticoids, defined as anything above that amount.

Overall survival and time to treatment failure were significantly higher in the low-dose group than the high-dose group (P = .002 for OS and P = .001 for TTF). Median overall survival was 23.3 months and time to treatment failure was 11.4 months in those given high-dose steroids. Median overall survival had not been reached in those given low-dose steroids.

While the findings are preliminary, the authors noted they may have implications for managing other immune-related adverse events. “Although the use of lower doses of immunosuppressive medications may be less of an option in many circumstances for other (immune-related adverse events), therapeutic parsimony would seem desirable with more tailored regimens as the biologic mechanisms underpinning these processes are further elucidated.”

SOURCE: Faje AT et al. Cancer. 2018 Jul 5.

Melanoma patients who took high doses of glucocorticoids for hypophysitis induced by the checkpoint-inhibitor ipilimumab had a lower overall survival time and a shorter time to treatment failure than did patients taking low-dose steroids for the adverse event, according to a new retrospective analysis in Cancer.

“Treatment with high-dose glucocorticoids does not appear to confer any obvious advantage to patients with IH (ipilimumab-induced hypophysitis) and may negatively affect tumor response to CPI (checkpoint-inhibitor therapy),” wrote Alexander Faje, MD, a neuroendocrinologist at Massachusetts General Hospital, Boston. “We recommend against the routine use of higher doses in these patients and that such treatment should be reserved for clinical indications like visual compromise or perhaps for intractable headache.”

Hypophysitis after treatment with a CTLA-4 inhibitor, such as ipilimumab, can approach 12%, though it is much less common with the checkpoint inhibitors that target PD-1 and PD-L1. Past studies examining the effects of glucocorticoids for immune-related adverse events have compared patients with severe events to those with minimal or no events. Since emergence of hypophysitis correlates with better overall survival, this is a flawed approach, the researchers said.

For their study, the researchers compared groups of patients with the same immune-related adverse events who received treatment with varying amounts of glucocorticoids.

They reviewed outcomes for 64 melanoma patients who had received ipilimumab monotherapy and were diagnosed with ipilimumab-induced hypophysitis treated in the Partners Healthcare system. Fourteen patients had received low-dose glucocorticoids, defined as a maximum average daily dose of 7.5 mg of prednisone or the equivalent. Fifty patients received high-dose glucocorticoids, defined as anything above that amount.

Overall survival and time to treatment failure were significantly higher in the low-dose group than the high-dose group (P = .002 for OS and P = .001 for TTF). Median overall survival was 23.3 months and time to treatment failure was 11.4 months in those given high-dose steroids. Median overall survival had not been reached in those given low-dose steroids.

While the findings are preliminary, the authors noted they may have implications for managing other immune-related adverse events. “Although the use of lower doses of immunosuppressive medications may be less of an option in many circumstances for other (immune-related adverse events), therapeutic parsimony would seem desirable with more tailored regimens as the biologic mechanisms underpinning these processes are further elucidated.”

SOURCE: Faje AT et al. Cancer. 2018 Jul 5.

Melanoma patients who took high doses of glucocorticoids for hypophysitis induced by the checkpoint-inhibitor ipilimumab had a lower overall survival time and a shorter time to treatment failure than did patients taking low-dose steroids for the adverse event, according to a new retrospective analysis in Cancer.

“Treatment with high-dose glucocorticoids does not appear to confer any obvious advantage to patients with IH (ipilimumab-induced hypophysitis) and may negatively affect tumor response to CPI (checkpoint-inhibitor therapy),” wrote Alexander Faje, MD, a neuroendocrinologist at Massachusetts General Hospital, Boston. “We recommend against the routine use of higher doses in these patients and that such treatment should be reserved for clinical indications like visual compromise or perhaps for intractable headache.”

Hypophysitis after treatment with a CTLA-4 inhibitor, such as ipilimumab, can approach 12%, though it is much less common with the checkpoint inhibitors that target PD-1 and PD-L1. Past studies examining the effects of glucocorticoids for immune-related adverse events have compared patients with severe events to those with minimal or no events. Since emergence of hypophysitis correlates with better overall survival, this is a flawed approach, the researchers said.

For their study, the researchers compared groups of patients with the same immune-related adverse events who received treatment with varying amounts of glucocorticoids.

They reviewed outcomes for 64 melanoma patients who had received ipilimumab monotherapy and were diagnosed with ipilimumab-induced hypophysitis treated in the Partners Healthcare system. Fourteen patients had received low-dose glucocorticoids, defined as a maximum average daily dose of 7.5 mg of prednisone or the equivalent. Fifty patients received high-dose glucocorticoids, defined as anything above that amount.

Overall survival and time to treatment failure were significantly higher in the low-dose group than the high-dose group (P = .002 for OS and P = .001 for TTF). Median overall survival was 23.3 months and time to treatment failure was 11.4 months in those given high-dose steroids. Median overall survival had not been reached in those given low-dose steroids.

While the findings are preliminary, the authors noted they may have implications for managing other immune-related adverse events. “Although the use of lower doses of immunosuppressive medications may be less of an option in many circumstances for other (immune-related adverse events), therapeutic parsimony would seem desirable with more tailored regimens as the biologic mechanisms underpinning these processes are further elucidated.”

SOURCE: Faje AT et al. Cancer. 2018 Jul 5.