# A Subgroup Analysis of Perioperative Pembrolizumab in Clinical Stage II Non-Small-Cell Lung Cancer from the Randomized KEYNOTE-671 Study

## TL;DR

Adding pembrolizumab to chemotherapy before and after surgery improves outcomes for stage II non-small-cell lung cancer patients.

## Contribution

This study provides subgroup analysis showing pembrolizumab benefits stage II NSCLC patients in the KEYNOTE-671 trial.

## Key findings

- Perioperative pembrolizumab improved event-free survival and major pathological response in stage II NSCLC.
- Treatment-related adverse events were higher with pembrolizumab but manageable and non-fatal.
- R0 resection rates were higher in the pembrolizumab group compared to chemotherapy alone.

## Abstract

Perioperative pembrolizumab plus neoadjuvant chemotherapy significantly improved outcomes versus neoadjuvant chemotherapy alone in early-stage, resectable, non-small-cell lung cancer (NSCLC) in the phase 3 KEYNOTE-671 study. We report outcomes in participants with baseline clinical stage II disease.

Participants with untreated, resectable, stage II-IIIB (N2) NSCLC were randomized 1:1 to receive pembrolizumab 200 mg or placebo every 3 weeks plus chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab or placebo for 13 cycles (∼9 months). Exploratory analyses were performed in participants with clinical stage II disease.

Of 797 randomized participants, 239 had stage II disease (pembrolizumab plus chemotherapy, n = 118; chemotherapy only, n = 121). Median study follow-up at data cutoff (August 19, 2024) was 49.9 (range, 32.2-75.3) months. Among participants who underwent surgery, 94/99 (94.9%) had R0 resections in the pembrolizumab arm and 89/103 (86.4%) in the neoadjuvant chemotherapy only arm. Event-free survival (hazard ratio [HR], 0.50; 95% CI, 0.34-0.74), overall survival (HR, 0.69; 95% CI, 0.43-1.11), major pathological response (difference, 25.7%; 95% CI, 15.3-35.9), and pathological complete response (difference, 21.3%; 95% CI, 13.2-30.2) were improved in the pembrolizumab arm. Grade 3-4 treatment-related adverse events (AEs) occurred in 50.0% of participants treated with pembrolizumab plus chemotherapy and 40.5% with chemotherapy; no treatment-related AEs led to death.

In participants with stage II NSCLC, perioperative pembrolizumab improved efficacy outcomes with manageable safety versus neoadjuvant chemotherapy alone, consistent with the overall KEYNOTE-671 population. These results support the use of this regimen in patients with stage II disease.

ClinicalTrials.gov, NCT03425643, registered/first posted on February 7, 2018 (https://www.clinicaltrials.gov/study/NCT03425643).

The addition of perioperative anti-programmed cell death protein 1 or anti-programmed cell death ligand 1 (anti-PD-[L]1) therapy to neoadjuvant chemotherapy has improved outcomes versus neoadjuvant chemotherapy alone in patients with early-stage, resectable, non-small-cell lung cancer (NSCLC).