KEYNOTE-671 Trial

Design - Phase 3 perioperative pembrolizumab + neoadjuvant chemo -> adjuvant pembrolizumab vs placebo, resectable stage II-IIIB NSCLC (NCT03425643).

EFS - HR 0.58 (median not reached vs 17.0 mo); 5-yr EFS 49.9% vs 26.5%.

OS - HR 0.72 (95% CI 0.56-0.93, P=0.0103); 5-yr OS 64.6% vs 53.6%.

Safety - Grade >=3 AEs 44.9% vs 37.3%; AE discontinuation 13.0% vs 6.5%.

Regulatory - FDA approved October 2023.

Sponsor / drug - Merck (MSD); pembrolizumab (Keytruda).

Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated July 21, 2026.

Event-Free Survival (EFS) — Dual Primary Endpoint (Investigator-Assessed)

Median: not reached (perioperative pembrolizumab) vs. 17.0 months (placebo + chemo). HR 0.58 (95% CI 0.46-0.72), P<0.001 5-year EFS (ELCC 2026 update) rate: 49.9% (pembrolizumab) vs. 26.5% (placebo). Primary analysis: EFS HR 0.58 (95% CI 0.46-0.72, P<0.001). pCR 18.1% vs. 4.0%; mPR 30.2% vs. 11.0%. 5-year update (ELCC 2026): median EFS 57.1 months (95% CI 38.0-NR) with pembrolizumab vs. 18.4 months (95% CI 14.8-22.1) with placebo; 5-year EFS rate 49.9% vs. 26.5%. pCR subgroup 5-yr EFS 80.8% vs. 55.7% (HR 0.37); non-pCR subgroup 5-yr EFS 42.9% vs. 25.2% (HR 0.69), demonstrating durable benefit even without pCR.

Overall Survival (OS)

HR 0.72 (95% CI 0.56-0.93), P=0.0103 OS HR 0.72 (95% CI 0.56-0.93, P=0.0103) — 28% reduction in risk of death. Primary OS analysis at ESMO 2024 (P=0.00488) and 5-year update at ESMO 2025 / ELCC 2026 consistent. 5-year OS rate 64.6% (95% CI 59.5-69.2) with pembrolizumab vs. 53.6% (95% CI 48.3-58.6) with placebo. Median follow-up 60.4 months (range 42.6-85.8).

Safety & Tolerability

Grade ≥3 adverse events: 44.9% (pembro) vs. 37.3% (placebo). Discontinuation due to AEs: 13.0% (pembro) vs. 6.5% (placebo). Key AEs: neutropenia / chemo-related cytopenia, immune-related AEs (thyroid, skin). Treatment-related deaths 0.8% (pembro) vs. 0.3% (placebo). AE profile consistent with chemotherapy + checkpoint inhibitor combinations.

Clinical Implications

✅ Perioperative pembrolizumab established as SOC for resectable stage II-IIIB NSCLC. KEYNOTE-671 demonstrated both EFS and OS benefits with perioperative pembrolizumab + chemotherapy, leading to FDA approval October 2023. Alongside AEGEAN (durvalumab), CheckMate-77T (nivolumab), and CheckMate-816 (neoadjuvant-only nivolumab), establishes perioperative immunotherapy as a core stage II-IIIB NSCLC strategy. Choice among regimens individualized by clinical and biomarker factors.

What is the KEYNOTE-671 trial?

KEYNOTE-671 is a Phase 3 randomized trial (NCT03425643) of perioperative pembrolizumab (Keytruda) - neoadjuvant pembrolizumab plus platinum-based chemotherapy followed by adjuvant pembrolizumab - versus neoadjuvant chemotherapy plus placebo in patients with resectable stage II-IIIB non-small cell lung cancer. Event-free survival and overall survival were the dual primary endpoints.

What were the efficacy results of KEYNOTE-671?

Event-free survival favored perioperative pembrolizumab with a hazard ratio of 0.58 (median not reached vs 17.0 months; 5-year EFS 49.9% vs 26.5%), and overall survival was significantly improved with a hazard ratio of 0.72 (95% CI 0.56-0.93, P=0.0103), a 28% reduction in the risk of death. The 5-year OS rate was 64.6% with pembrolizumab versus 53.6% with placebo.

Is perioperative pembrolizumab FDA approved for resectable NSCLC?

Yes. In October 2023 the FDA approved pembrolizumab (Keytruda) with neoadjuvant platinum-containing chemotherapy and then continued as a single agent as adjuvant treatment for resectable (tumors >=4 cm or node-positive) NSCLC, based on KEYNOTE-671.

What is the safety profile of the KEYNOTE-671 regimen?

Grade >=3 adverse events occurred in 44.9% of pembrolizumab patients versus 37.3% with placebo, and treatment discontinuation due to adverse events was 13.0% versus 6.5%. Treatment-related deaths were uncommon (0.8% vs 0.3%). The profile is consistent with a chemotherapy-plus-checkpoint-inhibitor combination, with immune-related events (thyroid, skin) among the notable toxicities.

How does KEYNOTE-671 fit with other perioperative NSCLC trials?

KEYNOTE-671 helped establish perioperative immunotherapy as a core approach for resectable stage II-IIIB NSCLC, alongside AEGEAN (durvalumab), CheckMate-77T (nivolumab), and the neoadjuvant-only CheckMate-816 (nivolumab). It is distinguished by demonstrating both an EFS and a statistically significant OS benefit.