NIVO+IPI and NIVO significantly improved PFS and OS vs. IPI alone in the CheckMate 067 study. Descriptively, NIVO+IPI showed longer OS than NIVO (hazard ratio: 0.88), with 2-year OS rates of 64% and 59%, respectively. Post-hoc analyses by region were performed to evaluate potential differences between patients (pts) treated in the EU and those treated in the USA.
Baseline patient characteristics, safety and efficacy were evaluated in the two highest enrolling regions (EU, 55% and USA, 22%) using data from the CheckMate 067 study. Minimum follow-up of the pts was 28 months.
EU pts were more likely to have M1c disease than USA pts (60% vs 53%), and more likely to have BRAF wild-type (WT) tumors (69% vs 59%). In a multivariate analysis, which adjusted for baseline factors, the only significant interaction between NIVO+IPI and NIVO was by region. Adjusted hazard ratios (HRs) for OS in the NIVO+IPI vs NIVO groups were 0.90 (0.66–1.23) for the EU and 0.53 (0.29–0.98) for the USA. Across all arms, 2-year OS rates were lower in the EU vs USA pts, particularly for pts with BRAF WT tumors (Table). In pts with BRAF mutant tumors, similar OS outcomes were observed between regions. Treatment exposure, safety, management of adverse events, and use of subsequent therapies did not differ substantially between the two regions. Objective response rates and progression-free survival were also similar between the two regions.Table:
|2-yr OS rates||ITT Population||EU||USA|
|Overall||BRAF WT||BRAF Mutant||Overall||BRAF WT||BRAF Mutant|
NIVO+IPI vs NIVO.
Differences in OS between the EU and the USA appear to be largely due to poorer survival outcomes in EU pts with BRAF WT tumors, which likely impacted OS differences between NIVO+IPI and NIVO in the overall population. Additional analyses by region, the first report of 3-year OS, as well as analyses by tumor mutational burden will be presented. Acknowledgement: J. Larkin and J.D. Wolchok contributed equally to this study.
Clinical trial identification
Legal entity responsible for the study
J-J. Grob: Served as a consultant for Bristol-Myers Squibb, GSK, Novartis, Roche, Merck, Amgen; participated on speakers’ bureau for Bristol-Myers Squibb, GSK, Roche; travel funding from Roche; recipient of research funding from Bristol-Myers Squibb and Roche. D. Schadendorf: Served as a consultant or advisor for Roche/Genentech, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck Serono, Sysmex, Amgen, Grunenthal Group, Immunocore; participated on a speakers’ bureau for Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Amgen, Incyte, Pierre Fabre; travel funding from Roche/Genentech, Bristol-Myers Squibb, Amgen, Merck, Merck Serono, Novartis; paid honoraria from Roche/Genentech, Novartis, Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, Sysmex, Immunocore, Grunenthal Group, Merck Serono, Agenus, Array BioPharma, LEO Pharma, Incyte, Pfizer, Pierre Fabre, Philogen, Regeneron; received institutional research funding from Bristol-Myers Squibb and Novartis. J. Wagstaff: Paid honoraria from Bristol-Myers Squibb, Merck, Roche, Astellas, Pfizer, Novartis; Consultant for Bristol-Myers Squibb, Merck, Roche, Astellas, Pfizer, Novartis; participated in speakers’ bureau for Bristol-Myers Squibb, Novartis, Astellas; travel funding from Bristol-Myers Squibb, Novartis, Astellas. I. Márquez-Rodas: Paid honoraria from Novartis, Roche, MSD, Bristol-Myers Squibb; served as a consultant for Novartis, Roche, MSD, Bristol-Myers Squibb, Amgen, Bioncotech; travel funding from MSD, Bristol-Myers Squibb, Amgen C. Lebbé: Served on an advisory board for Bristol-Myers Squibb, MSD, Roche, GSK, and Novartis. P.A. Ascierto: Served as a consultant for Bristol-Myers Squibb, Roche-GNE, MSD, Novartis, Array, Amgen, Merck-Serono, Pierre-Fabre; institution received research funding from Bristol-Myers Squibb, Roche-Genentech, Array F.S. Hodi: Employee: Dana-Farber Cancer Institute; consultant: MSD, Novartis, GNE/Roche, Amgen, EMD Serono; travel: Novartis and Bristol-Myers Squibb; patent pending royalties per inst policy; other Bristol-Myers Squibb & GNE/Roche; institutional research funding: Bristol-Myers Squibb, MSD, GNE/Roche, Novartis. J.C. Hassel: Payments for trial procedures according to study protocol from Bristol-Myers Squibb; honoraria: Bristol-Myers Squibb, MSD, Roche, GSK, Novartis, Amgen; research grant/funding: Bristol-Myers Squibb; travel: Bristol-Myers Squibb, MSD, Roche, GSK, Novartis, Amgen. D. Walker: Employed by Bristol-Myers Squibb; Immediate family member has stock or other ownership in Antares Pharma. R. Bhore: Employed by Bristol-Myers Squibb and owns stock in Bristol-Myers Squibb J. Larkin: Received research funding from Bristol-Myers Squibb, MSD, Novartis, and Pfizer; travel funding from Bristol-Myers Squibb, MSD, Pfizer, EISAI, GSK, and Roche. J.D. Wolchok: Consultant: Bristol-Myers Squibb, Merck, MedImmune, Ziopharm, Polynoma, Polaris, Jounce, GSK; Research funding: Bristol-Myers Squibb, Merck, MedImmune, GSK; patent issued for DNA vaccine of cancer in companion animals (co-investor). All other authors have declared no conflicts of interest.