A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer: Protocol-Specified Final Analysis of KEYNOTE-407

Lung Cancer

Paz-Ares L, et al. J Thorac Oncol 2020.


INTRODUCTION: In the randomized KEYNOTE-407 study (ClinicalTrials.gov, NCT02775435), pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel (chemotherapy) significantly improved overall survival (OS) and progression-free survival (PFS) versus placebo plus chemotherapy in patients with previously untreated metastatic squamous non-small-cell lung cancer (NSCLC). We report updated efficacy outcomes from the protocol-specified final analysis and, for the first time, progression on next-line of treatment.

METHODS: Eligible patients were randomized to chemotherapy plus either pembrolizumab (n=278) or placebo (n=281). After positive results from the second interim analysis, patients still receiving placebo could crossover to pembrolizumab monotherapy at time of confirmed progressive disease. Primary endpoints were OS and PFS. PFS-2 (time from randomization to progression on next-line treatment/death, whichever occurred first) was an exploratory endpoint.

RESULTS: After median (range) follow-up of 14.3 (0.1-31.3) months, pembrolizumab plus chemotherapy continued to demonstrate a clinically meaningful improvement over placebo plus chemotherapy in OS (median [95%CI], 17.1 [14.4‒19.9] versus 11.6 [10.1‒13.7] months; hazard ratio [HR (95%CI)], 0.71 [0.58‒0.88]) and PFS (median, 8.0 [6.3‒8.4] versus 5.1 [4.3‒6.0] months; HR [95%CI], 0.57 [0.47‒0.69]). PFS-2 was longer for patients randomized to first-line pembrolizumab plus chemotherapy (HR [95% CI], 0.59 [0.49‒0.72]). Grade 3‒5 adverse events occurred in 74.1% and 69.6% of patients receiving pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively.

CONCLUSION: Pembrolizumab plus chemotherapy continued to demonstrate substantially improved OS and PFS in patients with metastatic squamous NSCLC. The PFS-2 outcomes support pembrolizumab plus chemotherapy as a standard first-line treatment in patients with metastatic squamous NSCLC.