Overall Survival with Neoadjuvant Nivolumab plus Chemotherapy in Lung Cancer

Author(s): Patrick M. Forde, M.D.¹; Jonathan D. Spicer, M.D.²; Mariano Provencio, M.D.³; Tetsuya Mitsudomi, M.D.⁴; Mark M. Awad, M.D.⁵; Changli Wang, M.D.⁶; Shun Lu, M.D.⁷; Enriqueta Felip, M.D.⁸; Scott J. Swanson, M.D.⁹; Julie R. Brahmer, M.D.¹⁰; Keith Kerr, M.D.¹¹; Janis M. Taube, M.D.¹²; Tudor-Eliade Ciuleanu, M.D.¹³; Fumihiro Tanaka, M.D.¹⁴; Gene B. Saylors, M.D.¹⁵; Ke-Neng Chen, M.D.¹⁶; Hiroyuki Ito, M.D.¹⁷; Moishe Liberman, M.D.¹⁸; Claudio Martin, M.D.¹⁹; Stephen Broderick, M.D.²⁰; Lily Wang, M.D.²¹; Junliang Cai, M.D.²²; Quyen Duong, M.D.²³; Stephanie Meadows-Shropshire, M.D.²⁴; Joseph Fiore, M.D.²⁵; Sumeena Bhatia, M.D.²⁶; Nicolas Girard, M.D.²⁷;

Source: DOI: 10.1056/NEJMoa

Dr. Maen Hussein's Thoughts

There was a 28% reduction in mortality. Patients who achieved a complete response (CR) or clearance of circulating tumor DNA (ctDNA) also experienced better outcomes.

BACKGROUND

Neoadjuvant nivolumab plus chemotherapy significantly improved pathological complete response and event-free survival in patients with resectable non–small-cell lung cancer (NSCLC) in a phase 3 trial. Data are needed on overall survival.

METHODS

In this open-label, phase 3 trial, patients with stage IB to IIIA resectable NSCLC were randomly assigned to receive nivolumab plus chemotherapy or chemotherapy alone for three cycles, followed by surgery. The primary end points were event-free survival and pathological complete response. Here, we report the results of the planned analysis of overall survival. Research Summary Overall Survival with Neoadjuvant Nivolumab in NSCLC

RESULTS

A total of 358 patients were concurrently assigned to receive nivolumab plus chemotherapy (179 patients) or chemotherapy alone (179 patients). The final analysis of overall survival significantly favored neoadjuvant nivolumab plus chemotherapy over chemotherapy (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.523 to 0.998; P=0.048). At a median follow-up of 68.4 months, the 5-year overall survival was 65.4% with nivolumab plus chemotherapy and 55.0% with chemotherapy alone, with consistency across most subgroups. In exploratory analyses, the 5-year overall survival in the nivolumab-plus-chemotherapy group was 95.3% (95% CI, 82.7 to 98.8) among the patients with a pathological complete response and 55.7% (95% CI, 46.9 to 63.7) among those without such a response; survival was 75.0% among the patients with presurgery clearance of circulating tumor DNA (ctDNA) and 52.6% among those without such clearance. No new safety signals were observed.

CONCLUSIONS

Three cycles of neoadjuvant nivolumab plus chemotherapy significantly improved overall survival among patients with resectable NSCLC as compared with chemotherapy alone. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.)

Author Affiliations

¹Trinity St. James’s Cancer Institute, Trinity College Dublin, Dublin; ²McGill University Health Centre, Montreal; ³Hospital Universitario Puerta de Hierro, Madrid; ⁴Kindai University Faculty of Medicine, Ohno-Higashi, Osaka-Sayama, Japan; ⁵Memorial Sloan Kettering Cancer Center, New York; ⁶Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; ⁷Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; ⁸Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Universitat Autònoma Barcelona, Barcelona; ⁹Brigham and Women’s Hospital, Boston; ¹⁰Bloomberg–Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore; ¹¹Aberdeen Royal Infirmary, Aberdeen, United Kingdom; ¹²Bloomberg–Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore; ¹³Institutul Oncologic Prof. Dr. Ion Chiricuţă and University of Medicine and Pharmacy Iuliu Haţieganu, Cluj-Napoca, Romania; ¹⁴University of Occupational and Environmental Health, Kitakyushu, Japan; ¹⁵Charleston Oncology, Charleston, SC; ¹⁶State Key Laboratory of Molecular Oncology, Peking University Cancer Hospital and Institute, Beijing; ¹⁷Kanagawa Cancer Center, Yokohama, Japan; ¹⁸Centre Hospitalier de l’Université de Montréal, Montreal; ¹⁹Instituto Alexander Fleming, Buenos Aires; ²⁰Bristol Myers Squibb, Princeton, NJ; ²¹Institut du Thorax Curie-Montsouris, Institut Curie, Paris

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