Pembrolizumab Plus Chemotherapy Improves Long-Term Survival Outcomes in Metastatic NSCLC

Pembrolizumab plus chemotherapy yielded promising long-term results in overall survival (OS) and progression-free survival (PFS) for patients with previously untreated metastatic squamous non-small cell lung cancer, according to 5-year data from the KEYNOTE-407 trial.

Previously, the global, phase 3 KEYNOTE-407 reported pembrolizumab plus chemotherapy yielded significant improvements in OS and PFS compared with chemotherapy plus placebo. The current exploratory analysis aims to evaluate the efficacy and safety of pembrolizumab plus chemotherapy within this patient population at 5 years of follow-up. The dual primary end points were PFS and OS, with objective response rate (ORR) as a secondary end point.

The study analyzed data from 559 patients in the intent-to-treat population, randomized on a 1-to-1 basis to receive either pembrolizumab plus chemotherapy (n = 278) or placebo plus chemotherapy (n = 281). After a median follow-up of 56.9 months, pembrolizumab plus chemotherapy improved 5-year OS and PFS compared to placebo plus chemotherapy (OS: hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.59 to 0.85); PFS: HR, 0.62; 95% CI, 0.52 to 0.74). The ORR of the pembrolizumab arm was 62.2%, compared with 38.8% of the placebo arm. The benefits to PFS, OS and ORR were seen regardless of PD-L1 tumor proportion score. The objective response rate of patients who completed 35 cycles of pembrolizumab (n = 55) was 90.9%, and, after completion of 35 cycles, the 3-year OS rate was 69.5%.

Toxicity was similar in both treatment arms, with 98.6% of patients in the pembrolizumab arm and 98.2% of patients in the placebo arm experiencing an adverse event. Patients in the pembrolizumab arm experienced grade ≥3 adverse events at a slightly higher rate (74.8%) than patients in the placebo arm (70%). Additionally, immune-mediated adverse events and infusion reactions occurred at a higher rate with pembrolizumab (35.6%; grade ≥3 13.3%) compared with treatment with placebo (9.3%; grade ≥3 3.2%). No new treatment-related deaths were reported during this follow-up analysis since the previous final analysis. 

Dr Novello and colleagues concluded their findings “support pembrolizumab plus chemotherapy as a standard-of-care first-line treatment option for metastatic squamous NSCLC, regardless of PD-L1 expression.”

Source:

Novello S, Kowalski DM, Luft A, et al. Pembrolizumab plus chemotherapy in squamous non-small-cell lung cancer: 5-year update of the phase III KEYNOTE-407 study. J Clin Oncol. Published online February 3, 2023. doi:10.1200/JCO.22.01990