As reported in the Journal of Clinical Oncology by Silvia Novello, MD, PhD, and colleagues, the 5-year update of the phase III KEYNOTE-407 trial showed continued overall survival and progression-free survival benefit with the addition of pembrolizumab to chemotherapy in the first-line treatment of patients with metastatic squamous non–small cell lung cancer (NSCLC).
The primary analysis of the trial supported the October 2018 approval of pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel in the first-line treatment of patients with metastatic squamous NSCLC.
Silvia Novello, MD, PhD
Study Details
In the double-blind trial, 559 patients were randomly assigned to receive pembrolizumab at 200 mg (n = 278) or placebo (n = 281) plus carboplatin and paclitaxel or nab-paclitaxel once every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to 35 cycles. A total of 63% of patients in each group had a tumor proportion score (TPS) of ≥ 1%.
Patients in the placebo/chemotherapy group with confirmed progressive disease could cross over to receive pembrolizumab monotherapy for up to 35 cycles. Patients in the pembrolizumab/chemotherapy group who completed 35 cycles with stable disease or better could receive second-course pembrolizumab monotherapy for 17 cycles.
The primary endpoints were overall survival and progression-free survival on blinded independent central review.
Hazard ratios (HRs) for the pembrolizumab/chemotherapy group vs the placebo/chemotherapy group were 0.64 (P < .001) for overall survival and 0.56 (P < .001) for progression-free survival at primary analysis, and 0.71 (95% confidence interval [CI] = 0.58–0.88) and 0.57 (95% CI = 0.47–0.69), respectively, at the protocol-specified final analysis.
Key Findings
Median time from random assignment to data cutoff for the current analysis was 56.9 months (range = 49.9–66.2 months).
Overall survival remained better in the pembrolizumab/chemotherapy group (HR = 0.71, 95% CI = 0.59–0.85), with 5-year rates of 18.4% vs 9.7%. Among 55 patients in the pembrolizumab group who completed 35 cycles of treatment, the objective response rate was 90.9% and the 3-year overall survival rate after completion of 35 cycles was 69.5%.
Progression-free survival remained better in the pembrolizumab/chemotherapy group (HR = 0.62, 95% CI = 0.52–0.74), with 5-year rates of 10.8% vs 3.5%. Hazard ratios for overall survival and progression-free survival favored the pembrolizumab/chemotherapy group across all PD-L1 TPS subgroups.
Subsequent anticancer therapy was received by 109 patients in the pembrolizumab/chemotherapy group; 33 received anti–PD-1/PD-L1 therapy, including 12 who received on-study second-course pembrolizumab. Subsequent therapy was received by 172 patients in the chemotherapy group; 117 patients crossed over to pembrolizumab monotherapy on-study and an additional 26 received subsequent anti–PD-1/PD-L1 therapy outside the study (effective crossover rate = 50.9%).
Progression-free survival–2 (time from random assignment to subsequent progressive disease after next line of treatment or death from any cause) was better in the pembrolizumab/chemotherapy group (HR = 0.60, 95% CI = 0.50–0.72). Rates at 5 years were 18.1% vs 7.1%.
The investigators concluded, “Pembrolizumab plus chemotherapy maintained an overall survival and progression-free survival benefit vs placebo plus chemotherapy in previously untreated [patients with] metastatic squamous NSCLC and is a standard-of-care first-line treatment option for metastatic squamous NSCLC, regardless of PD-L1 expression.”
Dr. Novello, of the University of Turin, Azienda Ospedaliero Universitaria San Luigi, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.
