Association Between First-Line Immune Checkpoint Inhibition and Survival for Medicare-Insured Patients With Advanced Non-Small Cell Lung Cancer

Key Points Question Has the incorporation of checkpoint inhibitor immunotherapy into initial treatment of older Medicare-insured patients with advanced non–small cell lung cancer been associated with meaningful improvements in overall survival? Findings This cohort study included 19 529 patients s with Medicare coverage who initiated first systemic therapy for advanced lung cancer using 1 of 4 regimens of checkpoint inhibitor immunotherapy, cytotoxic chemotherapy, and combined chemoimmunotherapy. The median overall survival was 11.4 months among patients receiving pembrolizumab monotherapy and 12.9 months among patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy, both substantially shorter than observed in registrational trials, with an adjusted restricted mean survival time through 18 months of follow-up of 11 to 12 months for all 4 treatment groups. Meaning In this study, immunotherapy among older Medicare-insured patients with advanced non–small cell lung cancer was associated with shorter overall survival than observed in key clinical trials, providing patients and physicians with estimates of outcomes for older patients who have lung cancer and are being treated with immunotherapy.
Importance Immunotherapy is now a cornerstone of treatment for advanced non–small cell lung cancer (NSCLC), but its uptake and effectiveness among older patients outside clinical trials remain poorly understood. Objective To understand treatment patterns and evaluate the overall survival associated with checkpoint inhibitor immunotherapy, cytotoxic chemotherapy, and combined chemoimmunotherapy for older patients who have advanced NSCLC and Medicare coverage. Design, Setting, and Participants This retrospective cohort study included Medicare-insured patients in the US aged 66 to 89 years who initiated first palliative-intent systemic therapy for lung cancer between January 1, 2016, and December 31, 2018. Survival follow-up continued through March 31, 2020. A total of 19 529 patients who had advanced lung cancer and were insured by a Medicare fee-for-service plan were included in the analysis. Exposures Regimens included pembrolizumab monotherapy (n = 3079), combined platinum-based drug (ie, cisplatin or carboplatin [hereinafter, platinum]) and pemetrexed disodium (n = 5159), combined platinum and a taxane (ie, paclitaxel, nab-paclitaxel, or docetaxel) (n = 9866), and combined platinum, pemetrexed, and pembrolizumab (n = 1425), as ascertained using Medicare claims from the Centers for Medicare & Medicaid Services. Main Outcomes and Measures The primary outcome was overall survival, which was measured using the restricted mean survival time (RMST) with propensity score adjustment for clinical and sociodemographic characteristics. Median survival was also reported for comparison with outcomes from registrational trials. Results A total of 19 529 patients (54% male, 46% female; median age, 73.8 [interquartile range, 69.9-78.4] years) were identified for analysis. The uptake of pembrolizumab-containing regimens in the Medicare population was rapid, increasing from 0.7% of first-line treatments in the second quarter of 2016 to 42.4% in the third quarter of 2018. Patients who were older (≥70 years, 2484 [81%]), were female (1577 [51%]), and/or had higher Risk Stratification Index scores (highest quintile, 922 [30%]) were more likely to receive single-agent pembrolizumab than chemotherapy. After propensity score adjustment, pembrolizumab was associated with survival similar to platinum/pemetrexed (RMST difference, −0.2 [95% CI, −0.5 to 0.2] months) or platinum/taxane (RMST difference, −0.7 [95% CI, −1.0 to −0.4] months). Patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy also had adjusted survival similar to those receiving platinum/pemetrexed chemotherapy (RMST difference, 0.5 [95% CI, 0.1-0.9] months). The unadjusted median survival was 11.4 (95% CI, 10.5-12.3) months among patients receiving single-agent pembrolizumab, approximately 15 months shorter than observed among pembrolizumab-treated participants in the KEYNOTE-024 trial. The unadjusted median survival was 12.9 (95% CI, 11.8-14.0) months among patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy, approximately 10 months shorter than observed among platinum/pemetrexed/pembrolizumab–treated participants in the KEYNOTE-189 trial. Conclusions and Relevance Immunotherapy has been incorporated rapidly into treatment for patients with advanced NSCLC. However, survival estimates in the Medicare population are much shorter than those reported in registrational trials. These results provide contemporary estimates of survival for older patients with advanced NSCLC treated in routine practice, facilitating patient-centered decision-making.
This cohort study assesses the treatment patterns of and survival outcomes associated with checkpoint inhibitor immunotherapy, cytotoxic chemotherapy, and combined chemoimmunotherapy for older patients with advanced non–small cell lung cancer and Medicare coverage.