Previously, pembrolizumab plus chemotherapy demonstrated to significantly improve progression-free survival and overall survival in patients with metastatic squamous non-small-cell lung cancer (NSCLC), compared to chemotherapy alone. The updated results of KEYNOTE-407 were recently published in the Journal of Clinical Oncology. With five years of follow-up, pembrolizumab plus chemotherapy continued to provide a clinically meaningful survival benefit over chemotherapy, with manageable safety in these patients.
Squamous non-small-cell lung cancer (NSCLC) accounts for approximately 20 to 30% of all lung cancers and is associated with shorter survival than non-squamous NSCLC. The phase 3 KEYNOTE-407 study evaluated the efficacy and safety of combining pembrolizumab, an anti-programmed death 1 (anti-PD-1) monoclonal antibody, plus chemotherapy, compared with placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC. In the primary analysis after 7.8 months of follow-up, pembrolizumab plus chemotherapy significantly improved OS (HR:0.64) and PFS (HR: 0.56) over placebo plus chemotherapy. After sixteen additional months, pembrolizumab plus chemotherapy continued to show a clinically meaningful improvement in OS (HR: 0.71) and PFS (HR: 0.57) vs. placebo plus chemotherapy in the protocol-specified final analysis. This article reports the updated efficacy outcomes and safety from KEYNOTE-407, with approximately five years follow-up.
The phase 3 KEYNOTE-407 trial enrolled 559 adult patients with stage IV squamous NSCLC who had not received previous systemic treatment for metastatic NSCLC. Patients were randomised (1:1) to receive carboplatin and paclitaxel/nab-paclitaxel (chemotherapy) plus either pembrolizumab 200 mg (n=278) every three weeks or placebo (n=281). The dual primary endpoints were OS and PFS. Objective response rate (ORR) and duration of response (DOR) were secondary endpoints. PFS2 (time from random assignment to subsequent progressive disease after next line of treatment or death from any cause) was an exploratory endpoint.
After a median follow-up of 56.9 months, pembrolizumab plus placebo continued to demonstrate better PFS (HR: 0.62) and OS (HR: 0.71) compared to chemotherapy plus placebo. This translates into 5-year PFS rates of 10.8 vs. 3.5%, and into 5-year OS rates of 18.4 vs. 9.7% with pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively. This benefit was observed regardless of PD-L1 expression. Higher ORR rates (62.2% vs. 38.8%) and longer DOR (median, 9.0 vs. 4.9 months) were observed in the pembrolizumab plus chemotherapy arm. Median PFS2 was longer for pembrolizumab plus chemotherapy vs. placebo plus chemotherapy (HR: 0.60). Toxicity was manageable and no new treatment-related deaths were reported since the protocol-specified final analysis. Immune-mediated adverse events and infusion reactions occurred in 35.6% and 9.3% of patients, respectively.
The updated results of KEYNOTE-407 solidify the PFS and OS superiority of pembrolizumab and chemotherapyover chemotherapy alone in previously untreated, metastatic squamous NSCLC. This combination should be a first-line treatment option regardless of PD-L1 expression.