Addition of Pembrolizumab to Perioperative Chemotherapy Increased Survival, Response Among Patients With Resectable, Early-Stage NSCLC

According to a phase 3 study, the addition of perioperative pembrolizumab to chemotherapy significantly improved event-free survival, major pathological response, and pathological complete response compared to perioperative chemotherapy alone among patients with resectable, early-stage non-small cell lung cancer (NSCLC) with similar overall-survival (OS). 

Heather Wakelee, MD, Stanford University School of Medicine, Stanford Cancer Institute, Stanford California, and coauthors wrote prior research has indicated “a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone.” 

In this double-blind trial, 797 patients with early-stage NSCLC were randomized on a 1-to-1 basis to receive either 200 mg pembrolizumab (n = 397) or placebo (n = 400) once every 3 weeks, followed by 4 cycles of cisplatin-based chemotherapy and surgery, followed by another round of either pembrolizumab or placebo every 3 weeks for up to 13 cycles. Dual primary end points included event-free survival and OS. Secondary end points included pathological response, pathological complete response, and safety.  

At pre-specified first interim analysis, the median follow-up duration was 25.2 months and event-free survival at 24 months was 62.4% of patients in the pembrolizumab arm and 40.6% of patients in the placebo arm (hazard ratio [HR] for progression, recurrence, or death, 0.58%; 95% confidence interval [CI], 0.46 to 0.72; P < 0.001). The estimated 24-month OS was 80.9% in the pembrolizumab arm and 77.6% in the placebo arm (P = 0.02, which did not meet the significance criterion). A major pathological response occurred in 30.2% of patients in the pembrolizumab arm and 11% of patients in the placebo arm. (95% CI, 13.9 to 24.7; P < .0001; threshold, P = .0001). Pathological complete response occurred in 18.1% of patients in the pembrolizumab arm and 4% of patients in the placebo arm (95% CI, 10.1 to 18.7; P < .0001; threshold, P = .0001). 

Grade ≥3 treatment-related adverse events occurred in 44.9% of patients in the pembrolizumab arm and 37% of patients in the placebo arm. Grade 5 treatment-related adverse events were experienced by 1% and 0.8% of patients, respectively.

Dr Wakelee et al concluded, “Neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological response, and pathological complete response as compared to neoadjuvant chemotherapy alone followed by surgery,” among patients with resectable early-stage NSCLC.

Source: Wakelee H, Liberman M, Kato T, et al. Perioperative pembrolizumab for early-stage non–small cell lung cancer. N Engl J Med. Published online June 3, 2023. doi:10.1056/NEJMoa2302983