Perioperative Pembrolizumab Combo Improves Responses in NSCLC Subgroups

Subgroup data from KEYNOTE-671 support the use of perioperative pembrolizumab in stage II or III non–small cell lung cancer of any clinical nodal status.

Neoadjuvant pembrolizumab (Keytruda) plus chemotherapy followed by surgery and adjuvant pembrolizumab improved various response and survival outcomes among patients with early-stage resectable non–small cell lung cancer (NSCLC) regardless of clinical nodal status, according to updated subgroup data from the phase 3 KEYNOTE-671 trial (NCT03425643) presented at the IASLC 2025 World Conference on Lung Cancer (WCLC).¹

In the pembrolizumab and placebo arms, respectively, data showed a major pathological response (mPR) rate of 33.1% (95% CI, 25.6%-41.3%) vs 10.6% (95% CI, 6.0%-16.8%) among those with node-negative status and 28.2% (95% CI, 22.7%-34.3%) vs 11.2% (95% CI, 7.7%-15.7%) among those with node-positive status. Additionally, the pathologic complete response (pCR) rates were 20.3% (95% CI, 14.1%-27.7%) vs 4.9% (95% CI, 2.0-9.9%) in the node-negative population and 16.5% (95% CI, 12.1%-21.8%) vs 3.5% (95% CI, 1.6%-6.5%) in the node-positive group.

At 48 months, the event-free survival (EFS) rates were 57.1% in the pembrolizumab arm vs 34.9% in the placebo arm among those with node-negative disease (HR, 0.56; 95% CI, 0.40-0.77). In the node-negative population, pembrolizumab-based treatment produced an EFS benefit vs chemotherapy alone among patients with stage II (HR, 0.56; 95% CI, 0.35-0.68) and stage III disease (HR, 0.49; 95% CI, 0.31-0.60).

Among patients with node-positive status, the 48-month EFS rates were 49.2% in the pembrolizumab arm and 24.4% in the placebo arm (HR, 0.57; 95% CI, 0.45-0.72). In the node-positive group, an improvement in EFS occurred with pembrolizumab among those with stage II (HR, 0.39; 95% CI, 0.19-0.82) and stage III disease (HR, 0.59; 95% CI, 0.47-0.76).

The median overall survival (OS) was not reached (NR) in both the pembrolizumab arm (95% CI, NR-NR) and the placebo arm (95% CI, 47.8-NR) across the node-negative population (HR, 0.70; 95% CI, 0.47-1.04). Additionally, the OS rates at 48 months were 71.4% (95% CI, 63.3%-78.0%) vs 59.3% (95% CI, 50.0%-67.5%), respectively. Pembrolizumab-based treatment in the node-negative population produced an OS benefit among those with stage II (HR, 0.73; 95% CI, 0.42-1.25) and stage III disease (HR, 0.65; 95% CI, 0.36-1.18).

The median OS was NR in both the pembrolizumab arm (95% CI, 63.7-NR) and the placebo arm (95% CI, 45.7-NR) among those with node-positive status (HR, 0.77; 95% CI, 0.58-1.01). In each respective arm, the 48-month OS rates were 65.9% (95% CI, 59.3%-71.7%) vs 55.2% (95% CI, 48.3%-61.6%). Across the node-positive group, data revealed that pembrolizumab-based therapy improved OS among those with stage II (HR, 0.58; 95% CI, 0.21-1.56) and stage III disease (HR, 0.78; 95% CI, 0.58-1.05).

“At 4 years of follow-up, perioperative pembrolizumab was associated with numerically higher rates of R0 resection regardless of nodal status. Adverse effects [AEs] were manageable; there were no new signals identified,” Heather Wakelee, MD, a medical oncologist and Winston Chen and Phyllis Huang Professor at Stanford Medicine Healthcare, stated in the presentation.¹ “Efficacy and safety were consistent with the overall KEYNOTE-671, population after 4 years of follow-up, and these findings support the use of perioperative pembrolizumab in patients with stage II and III [NSCLC] regardless of clinical nodal status.”

In the double-blind KEYNOTE-671 trial, 797 patients were randomly assigned to receive neoadjuvant and adjuvant pembrolizumab or placebo in combination with neoadjuvant chemotherapy.² In the experimental arm, patients received neoadjuvant pembrolizumab at 200 mg intravenously every 3 weeks plus cisplatin with gemcitabine or pemetrexed. Adjuvant therapy in the experimental arm consisted of pembrolizumab every 3 weeks at 4 to 12 weeks following surgery.

The trial’s primary end points were EFS and OS. Secondary end points included mPR rate, pCR rate, AEs, and quality of life.

Patients 18 years and older with previously untreated and pathologically confirmed resectable stage II, IIIA, or IIIB NSCLC were eligible for enrollment on the trial. Other eligibility criteria included having an ECOG performance status of 0 or 1 and adequate organ function.

Regarding surgical outcomes in the pembrolizumab and placebo arms, respectively, the most common procedures were lobectomies in the node-negative group (75.2% vs 70.4%) as well as the node-positive group (80.7% vs 77.7%). Additionally, a majority of patients in each arm underwent an R0 resection in the node-negative (92.3% vs 85.2%) and node-positive populations (91.8% vs 83.7%).

References

1. Wakelee HA, Demedts I, Langleben A, et al. Perioperative pembrolizumab in non-small cell cancer (NSCLC): 4-Year outcomes by nodal status in the KEYNOTE-671 study. Presented at the IASLC 2025 World Conference on Lung Cancer (WCLC); September 6-9, 2025; Barcelona, Spain. MA04.04.
2. Efficacy and safety of pembrolizumab (MK-3475) with platinum doublet chemotherapy as neoadjuvant/​adjuvant therapy for participants with resectable stage II, IIIA, and resectable IIIB (T3-4N2) non-small cell lung cancer (MK-3475-671/​KEYNOTE-671). ClinicalTrials.gov. Updated December 3, 2024. Accessed September 8, 2025. https://tinyurl.com/3hp6d5yb