End-of-life immunotherapy on the rise for patients with metastatic cancer
Click Here to Manage Email Alerts
The percentage of patients with advanced cancers who died within a month of beginning immunotherapy rose significantly in the last decade, study results published in JAMA Oncology showed.
End-of-life–initiated (EOL-I) immunotherapy increased in patients with stage IV melanoma, non-small cell lung cancer and kidney cell carcinoma. However, the odds patients died within the same time frame dropped by approximately one-third if they received treatment at academic or high-volume centers.
“We are very much still learning how to best apply immunotherapy in practice,” Daniel M.Kerekes, MD, resident at Yale School of Medicine, told Healio. “While immunotherapy has truly revolutionized cancer treatment for many patients, it does not save all, and there is a cost to treatment for the patients it does not benefit.”
Background and methods
Between 18% and 33% of patients with a “wide range of cancers” who had immunotherapy died within a month of treatment, study investigators wrote.
Patients who receive EOL-I immunotherapy have increased hospitalization rates, ED visits and risk for death in the hospital. They can also experience financial burdens, as immunotherapy drugs can cost between $10,000 and $20,000 for a single dose.
“Just before this study, our group completed a study on the use of adjuvant immunotherapy in patients with stage IIIA melanoma,” Kerekes said.
“During that analysis, we found that academic and nonacademic facilities used immunotherapy with considerably different frequency for the same patient population, and that the use of immunotherapy in general was rapidly increasing,” he added. “Having uncovered these findings in the patient population with the earliest stage cancer for which immunotherapy was indicated at the time of that analysis, we were curious to see if these trends held true for patients on the other end of the disease spectrum — the ones with metastatic disease at the end of their lives.”
Kerekes and colleagues conducted a retrospective study using the National Cancer Database to determine patient characteristics, as well as clinical and risk factors associated with patients who had EOL-I immunotherapy.
Researchers limited the population to patients with stage IV melanoma, NSCLC and kidney cell carcinoma (KCC) — the cancers with the highest number of individuals with the longest FDA-approved experience with immunotherapy.
They examined the group, restricted to patients aged at least 18 years, from approval of those cancer’s treatments to 2019.
Results and what’s next
The cohort consisted of 242,371 patients (mean age, 67.9 ± 11.4 years; 56% men), 29.3% of whom received immunotherapy.
Most of the patients had NSCLC (81.4%), followed by KCC (10.2%) and melanoma (8.4%).
Patients with melanoma had the highest rate of immunotherapy treatments (41%), followed by NSCLC (29%) and KCC (28%).
The number of immunotherapy treatments increased for all three cancers during the study period, as did the rate of EOL-I immunotherapy (0.8% to 4.3% for melanoma; 0.9% to 3.2% for NSCLC; 0.5% to 2.6% for KCC).
EOL-I chemotherapy rates decreased over the same periods.
Mortality odds decreased 31% for patients treated at academic centers vs. nonacademic centers (OR = 0.69; 95% CI, 0.65-0.74), as well as 30% for patients treated at high-volume institutions vs. low-volume institutions (OR = 0.7; 95% CI, 0.65-0.76).
“Experience with these medications matters for patient outcomes, whether it be due to improved patient selection or improved management of the treatment and its side effects,” Kerekes told Healio. “To me, this emphasizes the importance of regular tumor boards in which clinicians and facilities that prescribe less immunotherapy can conference with those who prescribe more immunotherapy about the most appropriate treatment for complex patients.”
Patients across each cancer type who had their disease metastasize to at least three solid organs had EOL-I immunotherapy 3.8 times more often than patients whose cancer spread to just the lymph nodes (95% CI, 3.1-4.7).
Patients with melanoma and NSCLC had higher EOL-I immunotherapy percentages if the disease spread to any solid organ except the lungs vs. lymph nodes. They had increased odds of EOL-I immunotherapy if they had at least two comorbidities compared with none (P < .001).
Older patients with NSCLC had increased odds for EOL-I immunotherapy than younger patients (50-70 years of age, OR = 1.36; 95% CI, 1.15-1.62; 70 years of age and above, OR = 1.58; 95% CI, 1.31-1.89).
The analysis did not examine cause of death for patients included in the study cohort. “Lethal immune-related adverse events are rare (0.6% in published immune checkpoint inhibitor trials) and are not likely to explain most deaths contributing to the 4% to 10% 1-month mortality rate after immunotherapy initiation in this study,” the investigators wrote.
“All subgroups we investigated saw an overall survival benefit from immunotherapy as a group — even the oldest and sickest of the patient groups in our study saw a net survival benefit,” Kerekes said. “Despite some of the severe adverse effects we see, these drugs can be tolerated by some patients with very advanced disease and multiple comorbidities.”
Kerekes wants future research to investigate which patient groups have the most to gain from costly immunotherapy treatments.
“While we know that some patients will not receive any benefit from immunotherapy, we do not currently have strong data to help us determine who those patients are a priori,” he said. “We need much more information to spare those who will not see any benefit from the physical and financial costs of these systemic treatments.”
For more information:
Daniel M. Kerekes, MD, can be reached at daniel.kerekes@yale.edu.
Collapse
Read more about
Click Here to Manage Email Alerts