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

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 versus 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 versus 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 versus neoadjuvant chemotherapy in surgically relevant subgroups in early-stage NSCLC.