Updated results from the phase 3 KEYNOTE-671 trial reveal that neoadjuvant pembrolizumab (Keytruda) combined with chemotherapy, followed by surgery and adjuvant pembrolizumab, maintains a significant survival advantage in patients with resectable, early-stage non-small cell lung cancer (NSCLC). The 4-year data, presented at the 2024 ESMO Immuno-Oncology Annual Congress, underscore the durable benefits of this perioperative regimen compared to neoadjuvant chemotherapy and surgery alone.
The KEYNOTE-671 trial is a multicenter, double-blind, placebo-controlled study that randomized 797 patients with previously untreated, resectable stage II, IIIA, or IIIB NSCLC. Patients were assigned to either the pembrolizumab arm or the placebo arm, receiving neoadjuvant pembrolizumab or placebo plus cisplatin and either pemetrexed or gemcitabine for up to 4 cycles, followed by surgery and adjuvant pembrolizumab or placebo for up to 13 cycles.
Significant Improvement in Overall Survival and Event-Free Survival
At a median follow-up of 41.1 months, the median overall survival (OS) was not reached in the pembrolizumab arm, while it was not reached with placebo, demonstrating a 27% reduction in the risk of death (HR, 0.73; 95% CI, 0.58-0.92). The 4-year OS rates were 68.0% and 56.7% in the pembrolizumab and placebo arms, respectively.
Event-free survival (EFS) also showed marked improvement with the pembrolizumab regimen. The median EFS was 57.1 months (95% CI, 38.0-69.1) with pembrolizumab compared to 18.4 months (95% CI, 14.8-22.1) with placebo (HR, 0.57; 95% CI, 0.47-0.69). The 4-year EFS rates were 51.9% and 28.1%, respectively.
Expert Commentary
"These long-term follow-up results continue to support perioperative pembrolizumab as a standard-of-care treatment option for resectable, early-stage non–small cell lung cancer," said lead study author Margarita Majem Tarruella, MD, PhD, of the Department of Medical Oncology in the Hospital de la Santa Creu i Sant Pau, in Barcelona, Spain.
Safety Profile
The updated analysis revealed no new safety signals with the longer follow-up. Treatment-related adverse events (TRAEs) occurred in 96.7% and 95.5% of pembrolizumab- and placebo-treated patients, respectively, with grade 3 to 5 TRAEs in 45.2% and 37.8%, respectively. Serious TRAEs were reported in 18.4% and 14.8% of patients. Treatment discontinuations due to TRAEs occurred in 19.4% and 13.3% of patients in the pembrolizumab and placebo arms, respectively.
Immune-mediated adverse events and infusion reactions were more frequent in the pembrolizumab arm (26.0%) compared to the placebo arm (9.3%), with grade 3 to 5 events in 6.3% and 1.8% of patients, respectively. One patient death was reported from immune-mediated AEs/infusion reactions in the pembrolizumab arm.
Implications for Clinical Practice
The FDA approved perioperative pembrolizumab in October 2023 based on earlier data from KEYNOTE-671. These updated findings further solidify the role of perioperative pembrolizumab as a standard treatment approach for patients with resectable, early-stage NSCLC, offering a durable survival benefit.
