Continuation of Pembrolizumab with Additional Chemotherapy after Progression with PD-1/PD-L1 Inhibitor Monotherapy in Patients with Advanced NSCLC: A Randomized, Placebo-Controlled Phase II Study

Purpose: Although programmed cell death 1 (PD-1) or pro-arm (N ¼ 51). At the median follow-up duration of 10.5 months, grammed cell death ligand 1 (PD-L1) inhibitors have shown there was no statistical difference in PFS [median 4.1 months vs. survival benefits in patients with non–small cell lung cancer 5.9 months; HR ¼ 1.06; 95% confidence interval (CI), 0.69–1.62; (NSCLC), most patients progress. This study evaluated whether P ¼ 0.78) and overall survival (median 11.5 months vs. continuing pembrolizumab with additional chemotherapy after 12.0 months; HR ¼ 1.09; 95% CI, 0.66–1.83; P ¼ 0.73) between failure of prior PD-1/PD-L1 inhibitor extends survival. the pembrolizumab-chemotherapy and placebo-chemotherapy Patients and Methods: This placebo-controlled, double-blind, arms. In a subgroup with PD-L1 expression in ≥50% of tumor randomized phase II study enrolled patients with NSCLC who received cells and favorable clinical outcomes to prior PD-1/PD-L1 inhibone or two cytotoxic chemotherapy, including at least one platinumitor (partial response or 6 months or longer of stable disease), the doublet regimen, and progressed on second- or third-line PD-1/PD-L1 pembrolizumab-chemotherapy arm showed a higher 24-month inhibitor monotherapy as the last systemic therapy. Patients were survival rate than the placebo-chemotherapy arm (74% vs. 38%; randomized (1:1) to pembrolizumab or placebo plus chemotherapy, HR ¼ 0.52; 95% CI, 0.13–2.1; P ¼ 0.34). stratified by histology and clinical outcomes to prior PD-1/PD-L1 Conclusions: This study did not show a survival benefit with the inhibitor. The primary endpoint was progression-free survival (PFS). continuation of pembrolizumab with chemotherapy in patients whose Results: A total of 98 patients were randomized to the pemNSCLC progressed on second- or third-line PD-1/PD-L1 inhibitors. brolizumab-chemotherapy (N ¼ 47) and placebo-chemotherapy See related commentary by Tseng and Gainor, p.