Outcomes and Treatments of Patients With Non–Small Cell Lung Cancer Who Received Pembrolizumab

Importance: Two years of immunotherapy is the standard treatment for most patients with advanced non-small cell lung cancer. However, little is known about postimmunotherapy therapeutic strategies. Objective: To describe subsequent treatments and outcomes after pembrolizumab discontinuation following 2 years of therapy. Design, Setting, and Participants: This nationwide, population-based, retrospective cohort study used administrative health data from the French National Health Insurance database from patients who received a diagnosis of incident lung cancer between January 1, 2015, and December 31, 2022, who received pembrolizumab for 22 to 26 months and survived at least 29 months (landmark). The data cutoff was October 31, 2024. Data were analyzed in October 2025. Exposure: Treatment with pembrolizumab for 22 to 26 months, followed by observation of subsequent therapeutic management after discontinuation. Main Outcomes and Measures: Overall survival (OS) was defined as the time between landmark and death of any cause. Time to next treatment or death was defined as the time between the last pembrolizumab infusion and new treatment or death. Results: Among 41 498 patients who received frontline pembrolizumab for advanced disease, 5293 were alive at the landmark time and completed 2 years of treatment, and 1555 discontinued pembrolizumab at 2 years. The population of interest for this study included 1480 patients with at least 6 months of follow-up; the median (range) age was 63.0 (32.0-90.0) years, 537 (36.3%) were female, 943 (63.7%) were male, and 616 (41.6%) had received pembrolizumab monotherapy. After a median follow-up of 16 months (95% CI, 15.2-16.8) after the landmark, the OS rate at 48 months was 76.9% (95% CI, 72.7%-81.3%), and the time to next treatment or death rate at 48 months after pembrolizumab discontinuation was 49.9% (95% CI, 45.3%-55.0%). Overall, 387 patients (26.1%) received subsequent therapy. The first treatments after pembrolizumab discontinuation were chemotherapy (200 [51.7%]), radiotherapy (183 [47.3%]), and immunotherapy (4 [1.0%]). Considering all subsequent treatment lines, 19 patients (0.1%) received an immunotherapy rechallenge. Twelve months after initiation of the new treatment, the OS rates were 87.0% (95% CI, 81.6%-92.7%) for radiotherapy, 69.9% (95% CI, 61.1%-80.0%) for chemotherapy, and 61.4% (95% CI, 41.3%-91.4%) for immunotherapy. Conclusions: This cohort study found that, among long-term cancer survivors with advanced non-small cell lung cancer who were treated with pembrolizumab, survival outcomes were high and immunotherapy rechallenge was uncommon.