The phase III KEYNOTE-671 trial demonstrated that integrating perioperative pembrolizumab with cisplatin-based chemotherapy significantly improves event-free survival, major pathological response, and pathological complete response in patients with resectable non–small cell lung cancer. Published in The New England Journal of Medicine, the study evaluated a complete perioperative strategy combining pembrolizumab with chemotherapy before surgery, followed by surgery and continued pembrolizumab after resection.
A total of 797 patients with previously untreated, resectable stage II, IIIA, or IIIB disease with N2 involvement were randomized, with 397 assigned to perioperative pembrolizumab and 400 to placebo-based treatment. Patients received four cycles of pembrolizumab or placebo combined with cisplatin-based chemotherapy. Squamous tumors received cisplatin plus gemcitabine, while nonsquamous tumors received cisplatin plus pemetrexed. Surgery was followed by up to 13 cycles of pembrolizumab or placebo every three weeks.
Trial Design and Event-Free Survival Results
The trial’s dual primary endpoints were event-free survival and overall survival, with key secondary endpoints including major pathological response and pathological complete response. At a median follow-up of 25.2 months, the hazard ratio for progression, recurrence, or death was 0.58. Median event-free survival had not been reached in the pembrolizumab group compared to 17.0 months in the control group. At 24 months, 62.4% of patients receiving pembrolizumab were alive without an event, versus 40.6% in the control group.
Pathological Response and Tumor Eradication
Pembrolizumab substantially increased pathological tumor clearance at surgery, producing an approximately fourfold increase in pathological complete response, providing evidence of deeper tumor eradication before surgery. The clinical benefits captured by the event-free survival definition spanned the entire curative-intent pathway, including progression that prevented planned surgery, unresectable disease, postoperative recurrence, or death. The findings establish perioperative immunotherapy as an integral component of curative-intent management for selected stage II–III disease.
