Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

TLDR

Pembrolizumab, a humanized anti‑PD‑1 monoclonal antibody, shows antitumor activity in advanced non‑small‑cell lung cancer, especially in tumors with high PD‑L1 expression. In an open‑label, phase‑3 trial, 305 patients with untreated advanced NSCLC and ≥50 % PD‑L1 expression were randomized to pembrolizumab 200 mg q3 weeks or investigator‑chosen platinum‑based chemotherapy, with crossover allowed upon progression and progression‑free survival assessed by blinded central review. Pembrolizumab significantly extended median progression‑free survival to 10.3 months versus 6.0 months (HR 0.50), improved 6‑month overall survival (80.2 % vs 72.4 %, HR 0.60), increased objective response rate (44.8 % vs 27.8 %), prolonged median duration of response, and reduced treatment‑related adverse events compared with chemotherapy. Funded by Merck; trial registered at ClinicalTrials.gov NCT02142738.

Abstract

Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety.Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%).In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov number, NCT02142738 . ).