Patrick M Forde1, Jonathan Spicer1, Shun Lu1, Mariano Provencio1, Tetsuya Mitsudomi1, Mark M Awad1, Enriqueta Felip1, Stephen R Broderick1, Julie R Brahmer1, Scott J Swanson1, Keith Kerr1, Changli Wang1, Tudor-Eliade Ciuleanu1, Gene B Saylors1, Fumihiro Tanaka1, Hiroyuki Ito1, Ke-Neng Chen1, Moishe Liberman1, Everett E Vokes1, Janis M Taube1, Cecile Dorange1, Junliang Cai1, Joseph Fiore1, Anthony Jarkowski1, David Balli1, Mark Sausen1, Dimple Pandya1, Christophe Y Calvet1, Nicolas Girard1. 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.).
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.).
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.).
Authors: Adrienne M Luoma; Shengbao Suo; Yifan Wang; Lauren Gunasti; Caroline B M Porter; Nancy Nabilsi; Jenny Tadros; Andrew P Ferretti; Sida Liao; Cagan Gurer; Yu-Hui Chen; Shana Criscitiello; Cora A Ricker; Danielle Dionne; Orit Rozenblatt-Rosen; Ravindra Uppaluri; Robert I Haddad; Orr Ashenberg; Aviv Regev; Eliezer M Van Allen; Gavin MacBeath; Jonathan D Schoenfeld; Kai W Wucherpfennig Journal: Cell Date: 2022-07-07 Impact factor: 66.850
Authors: Yinjie Gao; Michelle M Stein; Matthew Kase; Amy L Cummings; Ramit Bharanikumar; Denise Lau; Edward B Garon; Sandip P Patel Journal: Cancer Immunol Immunother Date: 2022-07-26 Impact factor: 6.630
Authors: Marco de Scordilli; Anna Michelotti; Elisa Bertoli; Elisa De Carlo; Alessandro Del Conte; Alessandra Bearz Journal: Int J Mol Sci Date: 2022-06-29 Impact factor: 6.208