As reported in The Lancet by Spicer et al, overall survival results of the phase III KEYNOTE-671 trial indicate benefit of the addition of neoadjuvant pembrolizumab to chemotherapy followed by adjuvant pembrolizumab in patients with early-stage non–small cell lung cancer (NSCLC).
At the first interim analysis of the trial, adding perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved event-free survival.
Study Details
In the global double-blind trial, 797 patients were randomly assigned between May 2018 and December 2021 to the pembrolizumab group (n = 397) or the control group (n = 400). Patients received 4 cycles of neoadjuvant pembrolizumab at 200 mg or placebo every 3 weeks plus cisplatin-based chemotherapy, followed by surgery, and 13 cycles of adjuvant pembrolizumab at 200 mg or placebo every 3 weeks. Neoadjuvant chemotherapy consisted of cisplatin at 75 mg/m2 every 3 weeks and either gemcitabine at 1,000 mg/m2 on days 1 and 8 every 3 weeks (for squamous histology) or pemetrexed at 500 mg/m2 every 3 weeks (for nonsquamous histology). The dual primary endpoints were overall survival and event-free survival.
Key Findings
At the second interim analysis, median follow-up was 36.6 months (interquartile range = 27.6–47.8 months), representing approximately 1 additional year of follow-up since the prior analysis. At this analysis, 36-month overall survival rate was 71% (95% confidence interval [CI] = 66%–76%) in the pembrolizumab group vs 64% (95% CI = 58%–69%) in the control group (hazard ratio [HR] = 0.72, 95% CI = 0.56–0.93, P = .0052). Median overall survival was not reached vs 52.4 months, respectively.
Median event-free survival was 47.2 months (95% CI = 32.9 months to not reached) in the pembrolizumab group vs 18.3 months (95% CI = 14.8–22.1 months) in the placebo group (HR = 0.59, 95% CI = 0.48–0.72).
Subsequent anticancer therapy was received by 30% of the pembrolizumab group vs 52% of the control group, including PD-1 or PD-L1 inhibitors in 8% vs 29%.
Grade ≥ 3 treatment-related adverse events occurred in 45% of the pembrolizumab group vs 38% of the control group. Grade ≥ 3 immune-related adverse events occurred in 7% vs 2% of patients. Treatment-related adverse events led to death in four patients (1%) in the pembrolizumab group (atrial fibrillation, immune-mediated lung disease, pneumonia, and sudden cardiac death) and in three patients (1%) in the control group (acute coronary syndrome, pneumonia, and pulmonary hemorrhage).
The investigators concluded: “The significant overall survival benefit of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone coupled with a manageable safety profile support the use of perioperative pembrolizumab in patients with resectable, early-stage NSCLC.”
Jonathan D. Spicer, MD, of McGill University Health Centre, Montreal General Hospital, Montreal, is the corresponding author of The Lancet article.
Disclosure: The study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. For full disclosures of the study authors, visit www.thelancet.com.
