Content area
Abstract
Abstract
Background
Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non–small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.
Methods
In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients.
Results
The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P=0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group.
Conclusions
In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.)
Details
1 From the Bloomberg–Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Kimmel Cancer Center, Baltimore (P.M.F., S.R.B., J.R.B., J.M.T.); McGill University Health Center (J.S.), and Centre Hospitalier de l’Université de Montréal (M.L.) — both in Montreal; Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (S.L.), Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin (C.W.), and Peking University School of Oncology, Beijing Cancer Hospital, Beijing (K.-N.C.) — all in China; Hospital Universitario Puerta de Hierro, Madrid (M.P.); Kindai University Faculty of Medicine, Ohno-Higashi, Osaka-Sayama (T.M.), the University of Occupational and Environmental Health, Kitakyushu (F.T.), and Kanagawa Cancer Center, Yokohama (H.I.) — all in Japan; Dana–Farber Cancer Institute, Boston (M.M.A., S.J.S.); Vall d’Hebron Institute of Oncology, Barcelona (E.F.); Aberdeen Royal Infirmary, Aberdeen, United Kingdom (K.K.); Institutul Oncologic Prof. Dr. Ion Chiricuta and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania (T.-E.C.); Charleston Oncology, Charleston, SC (G.B.S.); University of Chicago Medicine, Chicago (E.E.V.); Bristol Myers Squibb, Princeton, NJ (C.D., J.C., J.F., A.J., D.B., M.S., D.P., C.Y.C.); and Institut du Thorax Curie-Montsouris, Institut Curie, Paris (N.G.).