Abstract 1381P
Background
The risk of recurrence after neoadjuvant CRT followed by surgery (trimodality therapy) remains high in EC/GEJC. Statistically significant and clinically meaningful improvement in disease-free survival (DFS) was demonstrated for nivolumab vs placebo (median, 22.4 vs 11.0 months [mo]; HR 0.69; 96.4% CI 0.56–0.86; P = 0.0003) with a well-tolerated safety profile in patients with resected EC/GEJC who received neoadjuvant CRT in the global, randomized, phase III CheckMate 577 study. Here, we report efficacy and safety with an additional 8 mo follow-up.
Methods
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 DFS. Exploratory endpoints included distant metastasis–free survival (DMFS).
Results
794 patients were randomized (nivolumab, 532; placebo, 262). In both groups, approximately 70% of patients had adenocarcinoma and almost 60% had a pathologic lymph node status ≥ypN1. With a minimum follow-up of 14 mo, adjuvant nivolumab showed a doubling of median DFS vs placebo (Table). DFS benefit was observed across multiple subgroups. Adjuvant nivolumab showed approximately 13 mo improvement in median DMFS compared to placebo (Table). The safety profile was consistent with that reported previously and most treatment-related adverse events (TRAEs) were grade 1 or 2 (Table). Table: 1381P
| Efficacy | Nivolumab N = 532 | Placebo N = 262 |
| Median DFS, mo (95% CI) | 22.4 (16.9–33.6) | 10.4 (8.3–13.9) |
| HR (95% CI) | 0.67 (0.55–0.81) | |
| 12 mo DFS rate, % (95% CI) | 62 (57–66) | 45.5 (39–51) |
| Median DMFS, mo (95% CI) | 29.4 (23.7–36.6) | 16.6 (11.4–24.9) |
| HR (95% CI) | 0.71 (0.58–0.87) | |
| 12 mo DMFS rate, % (95% CI) | 68 (64–72) | 56 (49.5–62) |
| Safety, n (%) | N = 532 | N = 260 |
| Any-grade TRAEs | 379 (71) | 122 (47) |
| Grade 3–4 | 74 (14) | 16 (6) |
| Serious TRAEs | 41 (8) | 7 (3) |
| Grade 3-4 | 31 (6) | 3 (1) |
| Any-grade TRAEs leading to discontinuation | 49 (9) | 8 (3) |
| Grade 3-4 | 26 (5) | 7 (3) |
Conclusions
With additional follow-up data, adjuvant nivolumab continues to demonstrate clinically meaningful efficacy and a well-tolerated safety profile, further supporting its use as a new standard of care for patients with resected EC/GEJC who received neoadjuvant CRT and have residual pathologic disease.
Clinical trial identification
NCT02743494.
Editorial acknowledgement
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
M. Moehler: Financial Interests, Personal, Other, Consulting or Advisory Role: Bayer; Financial Interests, Personal, Other, Consulting or Advisory Role: MSD; Financial Interests, Personal, Other, Consulting or Advisory Role: Merck Serono; Financial Interests, Personal, Other, Consulting or Advisory Role: Amgen; Financial Interests, Personal, Other, Consulting or Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Other, Consulting or Advisory Role: Pfizer; Financial Interests, Personal, Other, Consulting or Advisory Role: Roche; Financial Interests, Personal, Other, Consulting or Advisory Role: Lilly; Financial Interests, Personal, Other, Consulting or Advisory Role: Servier; Financial Interests, Personal, Other, Consulting or Advisory Role: BeiGene; Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Amgen; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Merck Serono; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Bayer; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: ASCO; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: German Cancer Society; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: MSD; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: ESMO; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Roche/Genentech; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: MSD Oncology; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: AstraZenca/MedImmune; Financial Interests, Personal, Other, Honoraria: Servier; Financial Interests, Personal, Other, Honoraria: Pierre Fabre; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Leap Therapeutics; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: MSD. J.A. Ajani: Financial Interests, Personal, Other, Consulting or Advisory Role: American Cancer Society; Financial Interests, Personal, Other, Consulting or Advisory Role: BeiGene; Financial Interests, Personal, Other, Consulting or Advisory Role: Vaccinogen; Financial Interests, Personal, Other, Consulting or Advisory Role: Insys Therapeutics; Financial Interests, Personal, Other, Consulting or Advisory Role: Merck; Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Taiho; Financial Interests, Personal, Research Grant: MedImmune; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Aduro Biotech; Financial Interests, Personal, Other, Honoraria: DAVA Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Acrotech Biopharma; Financial Interests, Personal, Other, Honoraria: Zymeworks; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Roche/Genentech; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Research Grant: Lilly/ImClone; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Delta-Fly Pharma; Financial Interests, Personal, Research Grant: Gilead Sciences; Financial Interests, Personal, Research Grant: Takeda; Financial Interests, Personal, Research Grant: ProLynx; Financial Interests, Personal, Research Grant: Zymeworks; Financial Interests, Personal, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Personal, Research Grant: Lilly. J. Kuzdzal: Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Roche. T. Zander: Financial Interests, Personal, Other, Consulting or Advisory Role: MSD; Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting or Advisory Role: ROCHE; Financial Interests, Personal, Other, Consulting or Advisory Role: Novartis. E. Van Cutsem: Financial Interests, Personal, Advisory Role: Array; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Personal, Advisory Board: Biocartis; Financial Interests, Personal, Advisory Board: Boehringer; Financial Interests, Personal, Advisory Board: Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: Halozyme; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck KGaA; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Sirtex; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Merck KGaA; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Servier. G. Piessen: Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting or Advisory Role: Nestle Health Sciences; Financial Interests, Personal, Other, Consulting or Advisory Role: MSD Oncology; Financial Interests, Personal, Other, Consulting or Advisory Role: Stryker; Financial Interests, Personal, Other, Consulting or Advisory Role: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Medtronic. G. Mendez: Financial Interests, Personal, Other, Consulting or Advisory Role: Merck; Financial Interests, Personal, Other, Consulting or Advisory Role: Roche; Financial Interests, Personal, Other, Consulting or Advisory Role: Servier; Financial Interests, Personal, Other, Consulting or Advisory Role: Lilly; Financial Interests, Personal, Other, Consulting or Advisory Role: MSD; Financial Interests, Personal, Other, Consulting or Advisory Role: Amgen; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Servier; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Servier; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bayer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche. J. Feliciano: Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Consulting or Advisory Role: Merck; Financial Interests, Personal, Other, Consulting or Advisory Role: Genentech; Financial Interests, Personal, Other, Consulting or Advisory Role: Pfizer; Financial Interests, Personal, Other, Consulting or Advisory Role: Lilly; Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb. S. Motoyama: Financial Interests, Personal, Other, Consulting or Advisory Role: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical Co., Ltd. A. LIÈVRE: Financial Interests, Personal, Other, Honoraria: Advanced Accelerator Applications; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: HalioDx; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Pierre Fabre; Financial Interests, Personal, Other, Honoraria: Sandoz; Financial Interests, Personal, Other, Honoraria: Servier; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Other, Consulting or Advisory Role: Advanced Accelerator Applications; Financial Interests, Personal, Other, Consulting or Advisory Role: Amgen; Financial Interests, Personal, Other, Consulting or Advisory Role: Bayer; Financial Interests, Personal, Other, Consulting or Advisory Role: Ipsen; Financial Interests, Personal, Other, Consulting or Advisory Role: Merck; Financial Interests, Personal, Other, Consulting or Advisory Role: Novartis; Financial Interests, Personal, Other, Consulting or Advisory Role: Pierre Fabre; Financial Interests, Personal, Other, Consulting or Advisory Role: Sandoz; Financial Interests, Personal, Other, Consulting or Advisory Role: Servier; Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte; Financial Interests, Personal, Other, Consulting or Advisory Role: Roche; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: IntegraGen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Advanced Accelerator Applications; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bayer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sandoz; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Servier; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Incyte; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer. H. Uronis: Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Leap Therapeutics; Financial Interests, Personal, Other, Employment and Stocks (Immediate Family Member): GeneCentric. E. Elimova: Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Zymeworks; Financial Interests, Institutional, Other, Consulting fees: Adaptimmune; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board: Zymeworks; Financial Interests, Personal, Other, Spouse employee: Merck Vaccines. K. Geboes: Financial Interests, Personal, Other, Consulting or Advisory Role: Ipsen; Financial Interests, Personal, Other, Consulting or Advisory Role: MSD; Financial Interests, Personal, Other, Consulting or Advisory Role: Servier; Financial Interests, Personal, Research Grant: Vifor; Financial Interests, Personal, Expert Testimony: Merck Darmstadt; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Ipsen; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Servier. J. Zhang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S. Soleymani: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. M. Lei: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Other, Patent, Royalties, Other intellectual property: Bristol Myers Squibb. K. Kondo: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb. J. Cleary: Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Invited Speaker, Travel, Accommodations, Expenses: Aglos; Financial Interests, Personal, Invited Speaker, Travel, Accommodations, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Tesaro; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Esperas Pharma; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Merus; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. R.J. Kelly: Financial Interests, Personal, Other, Consulting or Advisory Role: Novartis; Financial Interests, Personal, Other, Consulting or Advisory Role: Lilly; Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Consulting or Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting or Advisory Role: Merck; Financial Interests, Personal, Other, Consulting or Advisory Role: Medscape; Financial Interests, Personal, Other, Consulting or Advisory Role: Pieris Pharmaceuticals; Financial Interests, Personal, Other, Consulting or Advisory Role: Takeda; Financial Interests, Personal, Other, Consulting or Advisory Role: OncLive; Financial Interests, Personal, Other, Consulting or Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Other, Consulting or Advisory Role: EMD Serono; Financial Interests, Personal, Other, Consulting or Advisory Role: Eisai; Financial Interests, Personal, Other, Consulting or Advisory Role: Peerview; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Lilly. All other authors have declared no conflicts of interest.