First-line immunotherapy fails to improve OS outside of trials for older adults with NSCLC
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Rapid incorporation of pembrolizumab into the first-line treatment setting for older patients with advanced non-small lung cancer did not appear to result in an OS benefit among this population, according to a real-world analysis.
The results, published in JAMA Network Open, also showed that women treated with pembrolizumab (Keytruda, Merck) alone fared worse than those treated with chemotherapy alone, researchers noted.
“As an oncologist specializing in the treatment of patients with lung cancer, I have had the opportunity to observe the rapid implementation of immunotherapy into the treatment of patients with advanced non-small cell lung cancer over the last 5 years, based on clinical trials that demonstrated substantial improvements in survival,” Kenneth L. Kehl, MD, MPH, researcher in the division of population sciences in the department of medical oncology at Dana-Farber Cancer Institute and Harvard Medical School, told Healio. “We undertook the current study to better understand the implementation of immunotherapy and its association with outcomes in the older Medicare population, which suffers a disproportionate burden of lung cancer but tends to be underrepresented in clinical trials.”
Investigators from Dana-Farber and the Health Data Analytics Institute assessed whether the incorporation of immunotherapy into the front-line treatment setting corresponded to a meaningful improvement in OS among 19,529 Medicare-insured patients aged 66 to 89 years (median age, 73.8 years; 54% men) with advanced NSCLC.
Patients received first-line treatment with either pembrolizumab alone (n = 3,079), platinum chemotherapy with pemetrexed (n = 5,159) or with a taxane (n = 9,866), or a combination of platinum/pemetrexed and pembrolizumab (n = 1,425).
Researchers compared risk-adjusted restricted mean survival time (RMST) of patients treated between 2016 and 2018, with continued survival follow-up through March 31, 2020. OS, measured by RMST with propensity score adjustment for clinical and sociodemographic characteristics, served as the primary outcome.
Researchers found that uptake of pembrolizumab-containing regimens among Medicare beneficiaries increased rapidly, from 0.7% in the first-line setting during the second quarter of 2016 to 42.4% in the third quarter of 2018. Factors associated with a higher likelihood of receiving pembrolizumab monotherapy vs. chemotherapy included older age ( 70 years; 81% vs. 71%-76%), being a woman (51% vs. 43%-49%) and/or higher Risk Stratification Index score (highest quintile, 30% vs. 17%-22%).
Researchers observed similar survival, after propensity score adjustment, with pembrolizumab compared with platinum/pemetrexed chemotherapy (RMST difference, 0.2 months; 95% CI, 0.5 to 0.2) or platinum/taxane chemotherapy (RMST difference, 0.7 months; 95% CI, 1 to 0.4). Those who received the chemoimmunotherapy regimen also demonstrated similar adjusted survival compared with those who received platinum/pemetrexed chemotherapy (RMST difference, 0.5 months; 95% CI, 0.1 to 0.9).
Results showed median OS of 11.4 months (95% CI, 10.5-12.3) among patients treated with pembrolizumab alone — approximately 15 months less than reported among patients who received pembrolizumab in the KEYNOTE-024 trial, researchers noted.
In addition, the unadjusted median survival was 12.9 months (95% CI, 11.8-14) with pembrolizumab combined with chemotherapy — nearly 10 months less than observed with the chemoimmunotherapy regimen in the KEYNOTE-189 trial.
“These results inform prognostic discussions between patients and clinicians at the initiation of treatment and likely relate to patient selection factors. Patients who received immunotherapy were considerably more likely to be older and to suffer from a higher burden of comorbid conditions,” Kehl said. “These results reinforce the importance of designing clinical trials so that participants are representative of the population of patients who will ultimately use a given treatment. They provide realistic estimates of prognosis for older Medicare patients initiating first-line therapy for advanced NSCLC.”
Kehl said future research should examine whether novel treatments, including immunotherapy, may be expanding the population of older, potentially more frail patients receiving any treatment at all.
“This could improve population-level outcomes even as it decreases survival estimates in the treated population,” Kehl said.
For more information:
Kenneth L. Kehl, MD, MPH, can be reached at Harvard Medical School, 450 Brookline Ave., Boston, MA 02215; email: kenneth_kehl@dfci.harvard.edu.
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