Continuation of pembrolizumab with additional chemotherapy after progression with PD-1/PD-L1 inhibitor monotherapy in patients with advanced NSCLC.

Although PD-1 or PD-L1 inhibitors have shown survival benefits in patients with NSCLC, most patients progress. This study evaluated whether continuing pembrolizumab with additional chemotherapy after failure of prior PD-1/PD-L1 inhibitor extends survival.This placebo-controlled, double-blind, randomized phase II study enrolled patients with NSCLC who received one or two cytotoxic chemotherapy, including at least one platinum-doublet regimen, and progressed on second- or third-line PD-1/PD-L1 inhibitor monotherapy as the last systemic therapy. Patients were randomized (1:1) to pembrolizumab or placebo plus chemotherapy, stratified by histology and clinical outcomes to prior PD-1/PD-L1 inhibitor. The primary endpoint was progression-free survival (PFS).A total of 98 patients were randomized to the pembrolizumab-chemotherapy (N = 47) and placebo-chemotherapy arm (N = 51). At the median follow-up duration of 10.5 months, there was no statistical difference in PFS (median 4.1 months vs. 5.9 months; hazard ratio 1.06 [95% CI 0.69-1.62]; P = 0.78) and overall survival (median 11.5 months vs. 12.0 months; 1.09 [0.66-1.83]; P = 0.73) between the pembrolizumab-chemotherapy and placebo-chemotherapy arms. In a subgroup with PD-L1 expression in {greater than or equal to}50% of tumor cells and favorable clinical outcomes to prior PD-1/PD-L1 inhibitor (partial response or 6 months or longer of stable disease), the pembrolizumab-chemotherapy arm showed a higher 24-months survival rate than the placebo-chemotherapy arm (74% vs. 38%; 0.52 [0.13-2.1]); P = 0.34).This study did not show a survival benefit with the continuation of pembrolizumab with chemotherapy in patients whose NSCLC progressed on second- or third-line PD-1/PD-L1 inhibitors.