Perioperative Pembrolizumab for Early-Stage NSCLC

The use of neoadjuvant and adjuvant immunotherapy has been approved to treat patients with early-stage non–small-cell lung cancer (NSCLC), but the optimal regimen is unclear.

To test the use of neoadjuvant and adjuvant immune checkpoint inhibition with pembrolizumab in this setting, investigators conducted an industry-funded, international, randomized, double-blind, phase 3 trial (KEYNOTE-671) involving 796 patients (median age, 63; 70% men; 63% white; 31% Asian; 14% never smokers) with stage II, IIIA, or IIIB NSCLC. Half of the patients received neoadjuvant pembrolizumab plus chemotherapy followed by surgery and adjuvant pembrolizumab (pembrolizumab group). The other half received neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant placebo (placebo group). The dual primary endpoints were event-free survival (EFS) and overall survival (OS).

At median follow-up of 25.2 months, 24-month EFS was improved with pembrolizumab versus placebo (62.4% vs. 40.6%; hazard ratio 0.58; P<0.001), but the estimated 24-month OS was similar with pembrolizumab or placebo (80.9% and 77.6%, respectively). A major pathologic response occurred in more pembrolizumab recipients than placebo recipients (30.2% vs. 11.0%; P<0.0001), as did a pathologic complete response (18.1% vs. 4.0%; P<0.0001).

Grade 3–5 treatment-related adverse events (AEs) occurred in 44.9% of pembrolizumab recipients and in 37.3% of placebo recipients. Immune-mediated AEs occurred in 25.3% of pembrolizumab recipients and 10.5% of placebo recipients. Among the pembrolizumab group, 40.4% had completed adjuvant treatment, and 10.6% were still receiving adjuvant therapy. All other patients had discontinued pembrolizumab due to progression, toxicity, or preference.