The risk of recurrence after neoadjuvant CRT followed by surgery (trimodality therapy) remains high in EC/GEJC and there is no established adjuvant treatment. CheckMate 577 is the first global, randomized, double-blind, phase 3 study to report the efficacy and safety of a checkpoint inhibitor in the adjuvant setting after trimodality therapy for EC/GEJC.
Adults with resected (R0) stage II/III EC/GEJC who received neoadjuvant CRT and had residual pathologic disease were randomized 2:1 to nivolumab 240 mg or placebo Q2W for 16 weeks, followed by nivolumab 480 mg or placebo Q4W. Maximum treatment duration was 1 year. The primary endpoint was disease-free survival (DFS).
794 patients were randomized (nivolumab, 532; placebo, 262). Approximately 70% of patients had adenocarcinoma and almost 60% had a pathologic lymph node status ≥ypN1 in both groups. At a pre-specified interim analysis, adjuvant nivolumab showed a statistically significant improvement in DFS vs placebo (HR 0.69 [96.4% CI 0.56 -0.86]; P = 0.0003); median DFS was doubled (22.4 vs 11.0 mo, respectively; Table). The majority of treatment-related adverse events (TRAEs) were grade 1 or 2. The frequency of serious TRAEs and TRAEs leading to discontinuation were ≤ 9% with nivolumab and 3% with placebo (Table). Data including DFS rate and an analysis of DFS across pre-specified subgroups will be presented.
Efficacy Nivolumab Placebo Median DFS, mo (95% CI) HR (96.4% CI; Safety, n (%) Any-grade TRAEs Grade 3–4 Serious TRAEs Grade 3–4 TRAEs leading to discontinuation Grade 3–4
Adjuvant nivolumab is the first therapeutic to provide a statistically significant and clinically meaningful improvement in DFS vs placebo and a well-tolerated safety profile in patients with resected EC/GEJC, who have received neoadjuvant CRT. These results represent the first treatment advance in many years for these patients, potentially establishing adjuvant nivolumab as a new standard of care.
NCT02743494.
Writing and editorial assistance was provided by Patricia McChesney, PhD, CMPP, of Parexel International, funded by Bristol-Myers Squibb Company.
Bristol-Myers Squibb Company.
Bristol-Myers Squibb Company.
R.J. Kelly: Advisory/Consultancy, Research grant/Funding (institution), Advisory Board Member: Bristol Myers Squibb; Advisory/Consultancy, Advisory Board Member: Merck; Advisory/Consultancy, Advisory Board Member: Novartis ; Advisory/Consultancy, Research grant/Funding (institution), Advisory Board Member: Eli Lilly; Advisory/Consultancy, Advisory Board Member: Pieris Pharmaceuticals; Advisory/Consultancy, Advisory Board Member: Cardinal Health; Advisory/Consultancy, Advisory Board Member: Astellas; Advisory/Consultancy, Advisory Board Member: Takeda; Advisory/Consultancy, Advisory Board Member: Ono Pharmaceuticals; Advisory/Consultancy, Advisory Board Member: AstraZeneca. J.A. Ajani: Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb. J. Kuzdzal: Research grant/Funding (institution): Bristol Myers Squibb; Research grant/Funding (institution): Roche. T. Zander: Advisory/Consultancy, advisory boards: Bristol Myers Squibb; Advisory/Consultancy, advisory boards: MSD; Advisory/Consultancy, advisory boards: Roche; Advisory/Consultancy, advisory boards: Lilly; Advisory/Consultancy, advisory boards: Novartis. E. Van Cutsem: Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Servier; Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Merck Sharp & Dolme; Advisory/Consultancy, Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Merck. G. Piessen: Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Amgen. J.L. Feliciano: Advisory/Consultancy, Research grant/Funding (institution), consulting fees: AstraZeneca; Advisory/Consultancy, consulting fees: Genentech; Advisory/Consultancy, Research grant/Funding (institution), consulting fees: Bristol Myers Squibb; Advisory/Consultancy, consulting fees: Merck; Advisory/Consultancy, consulting fees: Eli Lilly. A. Lièvre: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, lectures, consulting, travel support: AAA; Honoraria (self), Advisory/Consultancy, lectures, consulting: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, lectures, consulting, travel support: Bayer; Honoraria (self), Travel/Accommodation/Expenses, lectures, travel support: Bristol Myers Squibb; Honoraria (self), lectures: Celgene; Honoraria (self), lectures: HalioDX; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, lectures, consulting, travel support: Ipsen; Honoraria (self), Advisory/Consultancy, lectures, consulting: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, lectures, consulting, travel support: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, lectures, consulting, travel support: Novartis; Honoraria (self), Advisory/Consultancy, lectures, consulting: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, lectures, consulting, travel support: Sandoz; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, lectures, consulting, travel support: Servier; Travel/Accommodation/Expenses, equipment supply: Integragen; Advisory/Consultancy, Travel/Accommodation/Expenses, consulting, travel support: Incyte; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, lectures, consulting, travel support: Roche; Travel/Accommodation/Expenses, travel support: Pfizer. H. Uronis: Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Advaxis; Research grant/Funding (institution): Bristol Myers Squibb. E. Elimova: Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Zymeworks; Spouse/Financial dependant: Merck Vaccines. C. Grootscholten: Research grant/Funding (institution): Bristol Myers Squibb. J. Zhang: Full/Part-time employment: Bristol Myers Squibb. L. Zhu: Full/Part-time employment: Bristol Myers Squibb. M. Lei: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. K. Kondo: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. J.M. Cleary: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol Myers Squibb; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Esperas Pharma. M. Moehler: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Adboards: Bristol Myers Squibb. All other authors have declared no conflicts of interest.