Clinical Characteristics and Surgical Outcomes of Patients Receiving Perioperative Pembrolizumab in KEYNOTE-671

Abstract

BACKGROUND The phase 3 KEYNOTE-671 study (NCT03425643) demonstrated significantly improved event-free survival (EFS) and overall survival with neoadjuvant pembrolizumab plus chemotherapy followed by surgery and adjuvant pembrolizumab vs neoadjuvant chemotherapy and surgery for early-stage non-small cell lung cancer (NSCLC). We describe participant characteristics, surgical outcomes, and EFS in surgically relevant subgroups. METHODS Participants with untreated, resectable, stage II-IIIB (N2) NSCLC were randomized 1:1 to neoadjuvant pembrolizumab 200 mg or placebo plus cisplatin-based chemotherapy every 3 weeks for 4 cycles, then surgery and adjuvant pembrolizumab or placebo for 13 cycles. Surgery was performed <= 20 weeks after first neoadjuvant dose (if 4 cycles of neoadjuvant therapy) or 4-8 weeks after last neoadjuvant dose (1-3 cycles); surgery beyond this was considered surgical delay. Adjuvant therapy began 4-12 weeks after surgery. EFS was assessed in the surgical population. RESULTS Of 397 participants randomized to pembrolizumab and 400 to placebo, 325 (82.1%) and 317 (79.4%), respectively, underwent surgery. At data cutoff (July 10, 2023), 4.9% (pembrolizumab) and 7.6% (placebo) of participants experienced surgical delay; 38.9% and 28.4%, respectively, experienced nodal downstaging; 78.8% and 75.1% underwent lobectomy; and 92.0% and 84.2% had R0 resections. Pembrolizumab improved EFS irrespective of disease stage, nodal status, and type of surgery vs chemotherapy. Eight participants (pembrolizumab, n = 6; placebo, n = 2) died <= 30 days after surgery from surgery-related adverse events. CONCLUSIONS Neoadjuvant pembrolizumab did not adversely affect surgical outcomes, was associated with numerically higher R0 resections, and improved EFS vs neoadjuvant chemotherapy in surgically relevant subgroups in early-stage NSCLC. (Ann Thorac Surg 2026;121:281-9) (c) 2026 Published by Elsevier Inc. on behalf of The Society of Thoracic Surgeons