Pembrolizumab versus Chemotherapy for PD L1 Positive Non Small Cell Lung Cancer.
BACKGROUND 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) METHODS 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. RESULTS 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% CONCLUSIONS 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
The New England journal of medicine