Pembrolizumab versus docetaxel for previously treated, PD L1 positive, advanced non small cell lung cancer (KEYNOTE 010) a randomised controlled trial
BACKGROUND Despite recent advances in the treatment of advanced non small cell lung cancer, there remains a need for effective treatments for progressive disease. We assessed the efficacy of pembrolizumab for patients with previously treated, PD L1 positive, advanced non small cell lung cancer. METHODS We did this randomised, open label, phase 2/3 study at 202 academic medical centres in 24 countries. Patients with previously treated non small cell lung cancer with PD L1 expression on at least 1% of tumour cells were randomly assigned (1:1:1) in blocks of six per stratum with an interactive voice response system to receive pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel 75 mg/m(2) every 3 weeks. The primary endpoints were overall survival and progression free survival both in the total population and in patients with PD L1 expression on at least 50% of tumour cells. We used a threshold for significance of p<0.00825 (one sided) for the analysis of overall survival and a threshold of p<0.001 for progression free survival. This trial is registered at ClinicalTrials.gov, number NCT01905657. FINDINGS Between Aug 28, 2013, and Feb 27, 2015, we enrolled 1034 patients: 345 allocated to pembrolizumab 2 mg/kg, 346 allocated to pembrolizumab 10 mg/kg, and 343 allocated to docetaxel. By Sept 30, 2015, 521 patients had died. In the total population, median overall survival was 10.4 months with pembrolizumab 2 mg/kg, 12.7 months with pembrolizumab 10 mg/kg, and 8.5 months with docetaxel. Overall survival was significantly longer for pembrolizumab 2 mg/kg versus docetaxel (hazard ratio [HR] 0.71, 95% CI 0.58 0.88; p=0.0008) and for pembrolizumab 10 mg/kg versus docetaxel (0.61, 0.49 0.75; p<0.0001) Median progression free survival was 3.9 months with pembrolizumab 2 mg/kg, 4.0 months with pembrolizumab 10 mg/kg, and 4.0 months with docetaxel, with no significant difference for pembrolizumab 2 mg/kg versus docetaxel (0.88, 0.74 1.05; p=0.07) or for pembrolizumab 10 mg/kg versus docetaxel (HR 0.79, 95% CI 0.66 0.94; p=0.004) Among patients with at least 50% of tumour cells expressing PD L1, overall survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel (median 14.9 months vs 8.2 months; HR 0.54, 95% CI 0.38 0.77; p=0.0002) and with pembrolizumab 10 mg/kg than with docetaxel (17.3 months vs 8.2 months; 0.50, 0.36 0.70; p<0.0001) Likewise, for this patient population, progression free survival was significantly longer with pembrolizumab 2 mg/kg than with docetaxel (median 5.0 months vs 4.1 months; HR 0.59, 95% CI 0.44 0.78; p=0.0001) and with pembrolizumab 10 mg/kg than with docetaxel (5.2 months vs 4.1 months; 0.59, 0.45 0.78; p<0.0001) Grade 3 5 treatment related adverse events were less common with pembrolizumab than with docetaxel (43 [13% of 339 patients given 2 mg/kg, 55 [16% of 343 given 10 mg/kg, and 109 [35% of 309 given docetaxel) INTERPRETATION Pembrolizumab prolongs overall survival and has a favourable benefit to risk profile in patients with previously treated, PD L1 positive, advanced non small cell lung cancer. These data establish pembrolizumab as a new treatment option for this population and validate the use of PD L1 selection. FUNDING Merck Co.
The Lancet