Long-term survival in patients (pts) with advanced NSCLC in the KEYNOTE-010 study overall and in pts who completed two years of pembrolizumab (pembro)

Abstract

Background: KEYNOTE‐010 (NCT01905657) is a global, open‐label, phase 2/3 study of pembro 10 mg/kg or 2 mg/kg Q3W vs docetaxel in pts with previously treated advanced NSCLC with PD‐L1 TPS ≥1%. Pembro improved OS vs docetaxel in the PDL1 TPS ≥1% and≥50% co‐primary analyses (median follow‐up, 13.1 mo), with no difference between pembro doses. We present updated OS for the study overall and results for pts who completed 35 cycles (∼2 y) of pembro. Methods: Pts>18 years with previously treated advanced NSCLC with PD‐L1 TPS ≥1% were randomized (1:1:1) to pembro 10 mg/kg or 2 mg/kg Q3W, or docetaxel 75 mg/m2 Q3W. Pts received pembro for 35 cycles or until disease progression/intolerable toxicity. After the primary analysis, crossover from docetaxel to pembro was allowed. Response was assessed every 9 wk (RECIST 1.1 by independent central review), and survival every 2 mo after treatment ended. OS was a primary endpoint. Pembro doses were pooled. Results: As of March 16, 2018, median (range) follow‐up was 42.5 (35.2‐53.2) mo. Among all pts (N=1033), pembro improved OS vs docetaxel (HR, 0.69; 95% CI, 0.60‐ 0.80; P<0.00001), with median (95% CI) OS of 11.8 (10.4‐13.1) mo vs 8.4 (7.6‐9.5) mo, and 36‐mo OS rate of 23% vs 11%, respectively. Incidence of grade 3‐5 treatmentrelated AEs was similar to the primary analysis: 16% of pts in the pembro group and 36% in the docetaxel group had grade 3‐5 treatment‐related AEs (0.7% and 1.6%, respectively, had grade 5 AEs). 22% and 9% of pts, respectively, had immune‐mediated AEs and infusion reactions. Among 79 pts who completed 35 pembro cycles, the 36‐mo OS rate was 99% and 95% had PR/CR as best response. Response was ongoing in 44 pts (59%); median duration of response was not reached (range, 1+ to 46+ mo). 25 of 79 pts (32%) had PD (investigator review) after stopping 35 cycles of treatment, 13 of whom started second course pembro. Conclusions: With an additional 30‐mo follow‐up from the primary analyses, pembro continued to prolong OS vs docetaxel in pts with previously treated, PD‐L1‐expressing advanced NSCLC, with manageable long‐term safety. Most pts who completed 2 y of pembro had durable response, and the majority of pts who had PD after stopping 35 cycles of pembro were able to receive a second course of pembro.