Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer

Authors

Heather Wakelee
Moishe Liberman
Terufumi Kato
Masahiro Tsuboi
Se-Hoon Lee
Shugeng Gao
Ke-Neng Chen
Christophe Dooms
Margarita Majem
Ekkehard Eigendorff
Gastón L Martinengo
Olivier Bylicki
Delvys Rodríguez-Abreu
Jamie E Chaft
Silvia Novello
Jing Yang
Steven M Keller
Ayman Samkari
Jonathan D Spicer
KEYNOTE-671 Investigators

Publication Date

8-10-2023

Journal

New England Journal of Medicine

Abstract

BACKGROUND: Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone.

METHODS: We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety.

RESULTS: A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P

CONCLUSIONS: Among patients with resectable, early-stage NSCLC, neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological response, and pathological complete response as compared with neoadjuvant chemotherapy alone followed by surgery. Overall survival did not differ significantly between the groups in this analysis. (Funded by Merck Sharp and Dohme; KEYNOTE-671 ClinicalTrials.gov number, NCT03425643.).

Keywords

Humans, Adjuvants, Immunologic, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Cisplatin, Combined Modality Therapy

Comments

Supplementary Materials

PMID: 37272513