Five-Year Real-World Outcomes With Frontline Pembrolizumab Monotherapy in PD-L1 Expression ≥50% Advanced NSCLC

Background In clinical trials, frontline pembrolizumab for advanced NSCLC has demonstrated durable, clinically meaningful, long-term survival benefits over chemotherapy. Our objective was to evaluate 5-year survival rates outside the idealized setting of clinical trials for advanced/metastatic NSCLC treated with frontline pembrolizumab monotherapy. Methods Using a nationwide, electronic health record-derived, deidentified database in the United States, we studied adult patients with advanced/metastatic NSCLC (unresectable stage IIIB/IIIC, or stage IV), with PD-L1 expression ≥50%, no documented EGFR, ALK, or ROS1 genomic alteration, and ECOG performance status of 0-1 initiating frontline pembrolizumab monotherapy from 1-Nov-2016 through 31-March-2020, excluding those in clinical trials. Kaplan-Meier was used to determine overall survival (OS). Data cutoff was 31-May-2023. Results A total of 804 patients were eligible for the study, including 404 women (50%); median age was 72 years (range, 38-85 years), with 310 patients (39%) ≥75 years old. Median follow-up time from pembrolizumab initiation to data cutoff was 60.5 months (range, 38.0-78.7). At data cutoff, 549 patients (68%) had died. Median OS was 19.2 months (95% CI, 16.6-21.4), and survival rate at 5 years was 25.1% (95% CI, 21.7-28.7). Overall, 266 patients (33%) received one or more subsequent regimens, most commonly an anti-PD-(L)1 agent (as monotherapy or combination therapy) or platinum-based chemotherapy. Conclusions With 5-year follow-up in a real-world population, frontline pembrolizumab monotherapy continues to demonstrate long-term effectiveness, with survival outcomes consistent with those of pivotal clinical trials, for treating patients with advanced NSCLC with PD-L1 expression of ≥50% and no EGFR, ALK, or ROS1 genomic alteration.MicroabstractCompared with chemotherapy in clinical trials, immunotherapies such as pembrolizumab improve long-term survival of patients with unresectable, advanced non-small cell lung cancer (NSCLC). This study evaluated long-term real-world outcomes with frontline pembrolizumab for 804 patients with advanced NSCLC. The 5-year survival rate of 25% was consistent with key clinical trials and demonstrated long-term effectiveness of frontline pembrolizumab for these patients.