NIVO has shown improved recurrence-free survival (RFS) vs IPI in patients (pts) with resected stage III/IV melanoma in the phase III CheckMate 238 study. Updated 48-mo RFS and distant metastases-free survival (DMFS) and primary OS are presented.
Pts aged ≥ 15 y with completely resected stage IIIB/C or IV melanoma were stratified by stage and tumor programmed death ligand 1 (PD-L1) status and randomized 1:1 to NIVO (3 mg/kg Q2W; n = 453) or IPI (10 mg/kg Q3W for 4 doses, Q12W thereafter; n = 453) for ≤ 1 y or until disease recurrence/unacceptable toxicity. The primary endpoint was RFS. Secondary endpoints included OS and safety; DMFS in stage III disease was exploratory.
At 48 mo of follow-up, NIVO continued to demonstrate superior RFS vs IPI (HR 0.71; 95% CI 0.60–0.86;
NIVO continued to demonstrate improved RFS and DMFS vs IPI at 48 mo in pts with stage III/IV melanoma at high risk of recurrence. OS events (n = 211) were lower than anticipated (n = 302). OS rates were similar to NIVO and IPI, although use of subsequent IO therapy was higher in the IPI arm. Late-emergent TRAEs were consistent with the established safety profile of NIVO and IPI, with more events reported with IPI. Data are HR (95% CI) for NIVO vs IPI; aStratified; b95.03% CI; cAJCC 7th ed.; Ind, indeterminate.
RFS DMFS OS ITT populationa 0.71 (0.60–0.86) 0.79 (0.63–0.99) 0.87 (0.66–1.14)b Stagec IIIB 0.70 (0.50–0.98) 0.78 (0.54–1.14) 0.88 (0.53–1.47) IIIC 0.74 (0.57–0.96) 0.82 (0.62–1.09) 0.96 (0.67–1.39) IV 0.74 (0.49–1.11) - 0.72 (0.38–1.38) PD-L1 ≥ 1% 0.68 (0.54–0.86) 0.77 (0.58–1.04) 0.73 (0.51–1.04) < 1%/ind 0.76 (0.57–1.02) 0.80 (0.56–1.14) 1.09 (0.72–1.67) ≥ 5% 0.67 (0.47–0.96) 0.79 (0.51–1.22) 0.74 (0.43–1.27) < 5%/ind 0.74 (0.59–0.91) 0.80 (0.61–1.04) 0.92 (0.68–1.26) Mutant 0.79 (0.60–1.05) 0.82 (0.57–1.16) 1.13 (0.73–1.74) Wild-type 0.69 (0.53–0.91) 0.79 (0.57–1.09) 0.76 (0.51–1.12)
NCT02388906.
Writing and editorial assistance were provided by Jessica Augello, PhD, and Michele Salernitano of Ashfield Healthcare Communications, funded by Bristol-Myers Squibb Company.
Bristol-Myers Squibb Company.
Bristol-Myers Squibb Company.
J. Weber: Honoraria (self), Advisory/Consultancy: Celldex; Honoraria (self), Advisory/Consultancy: Ichor Medical Systems; Honoraria (self), Advisory/Consultancy: cCam Biotherapeutics; Honoraria (self), Advisory/Consultancy: Lion Biotechnologies; Honoraria (self), Advisory/Consultancy: Pieris Pharmaceuticals; Honoraria (self), Advisory/Consultancy, Shareholder/Stockholder/Stock options: Altor BioScience; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genentech; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): GSK; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Shareholder/Stockholder/Stock options: CytomX Therapeutics; Honoraria (self), Advisory/Consultancy: Nektar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Shareholder/Stockholder/Stock options: Biond; Honoraria (self): Medivation; Honoraria (self): Sellas Life Sciences; Honoraria (self): WindMIL; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Incyte; Licensing/Royalties, Named on patent submitted by Moffitt Cancer Center for an IPILIMUMAB biomarker issued: Moffitt Cancer Center; Licensing/Royalties, Named on a patent from Biodesix for a PD-1 antibody biomarker issued: Biodesix. M. Del Vecchio: Advisory/Consultancy: Novartis; Advisory/Consultancy: BMS; Advisory/Consultancy: Merck; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pierre Fabre. M. Mandala: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Honoraria (self), Advisory/Consultancy: MSD Oncology. H. Gogas: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self): Novartis; Honoraria (self), Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy: Amgen; Travel/Accommodation/Expenses: Roche. A.M. Arance Fernandez: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Amgen. S. Dalle: Advisory/Consultancy, Research grant/Funding (institution): MDS; Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Research grant/Funding (institution): Roche; Research grant/Funding (institution): AstraZeneca; Spouse/Financial dependant, An immediate family member is employed by Sanofi Pasteur: Sanofi Pasteur. C.L. Cowey: Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Regeneron; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Caudex; Research grant/Funding (institution): Array; Research grant/Funding (institution): Amgen. M. Schenker: Research grant/Funding (self), Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (self), Research grant/Funding (institution): MSD; Research grant/Funding (self), Research grant/Funding (institution): Roche; Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (self), Research grant/Funding (institution): Novartis; Research grant/Funding (self), Research grant/Funding (institution): Eli Lilly; Research grant/Funding (self), Research grant/Funding (institution): AbbVie; Research grant/Funding (self), Research grant/Funding (institution): Regeneron; Research grant/Funding (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (self), Research grant/Funding (institution): Merck Serono; Research grant/Funding (self), Research grant/Funding (institution): Mylan; Research grant/Funding (self), Research grant/Funding (institution): Samsung; Research grant/Funding (self), Research grant/Funding (institution): Gilead; Research grant/Funding (self), Research grant/Funding (institution): Amgen. J-J. Grob: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Amgen; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Merck; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi. V. Chiarion Sileni: Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Pierre Fabre. I. Márquez-Rodas: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharpe & Dohme; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy: Sanofi; Advisory/Consultancy: INCYTE; Advisory/Consultancy: Merck SERONO; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Bioncotech. M.O. Butler: Advisory/Consultancy: Merck & Co., Inc.; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novartis; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Leadership role, Safety Review Board Member: Adaptimmune; Advisory/Consultancy, Leadership role, Safety Review Board Member: GlaxoSmithKline. M. Maio: Honoraria (self), Advisory/Consultancy, Patient Fees to my institution: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (institution), Advisory/Consultancy: Merck Serono; Honoraria (institution), Advisory/Consultancy: GlaxoSmithKline; Honoraria (institution), Advisory/Consultancy: Incyte. M. Middleton: Advisory/Consultancy: Amgen; Honoraria (self), Research grant/Funding (institution): Roche; Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Millennium; Research grant/Funding (institution), Travel/Accommodation/Expenses: Immunocore; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, IDSMC: Merck/Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (institution): Rigontec (acquired by MSD); Research grant/Funding (institution): Regeneron; Advisory/Consultancy, Research grant/Funding (institution): BioLineRx; Advisory/Consultancy, Research grant/Funding (institution): Array Biopharma (now Pfizer)); Advisory/Consultancy: Kineta; Advisory/Consultancy: Silicon Therapeutics; Research grant/Funding (self), Travel/Accommodation/Expenses: Replimune. M. Lobo: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb; Shareholder/Stockholder/Stock options: Advaxis Immunotherapies. V. de Pril: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. J. Larkin: Advisory/Consultancy, Research grant/Funding (institution): Achilles Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boston Biomedical; Advisory/Consultancy: Eisai; Advisory/Consultancy: EUSA Pharma; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Imugene; Advisory/Consultancy: Incyte; Advisory/Consultancy: iOnctura; Advisory/Consultancy: Kymab; Advisory/Consultancy: Merck Serono; Advisory/Consultancy, Research grant/Funding (self): Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (self): Nektar; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy: Secarma; Advisory/Consultancy: Vitaccess; Advisory/Consultancy: Covance; Advisory/Consultancy, Research grant/Funding (self): Immunocore; Advisory/Consultancy: Aveo; Advisory/Consultancy: Pharmacyclics. P.A. Ascierto: Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): Roche/Genentech; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (self): Array BioPharma; Advisory/Consultancy, Leadership role: Merck Serono; Advisory/Consultancy: Newlink Genetics; Advisory/Consultancy: Genmab; Advisory/Consultancy: Incyte; Advisory/Consultancy: MedImmune; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Syndax; Advisory/Consultancy: Sun Pharma; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Idera; Advisory/Consultancy: Ultimovacs; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Immunocore; Advisory/Consultancy: 4SC; Advisory/Consultancy: Alkermes; Advisory/Consultancy: Italfarmaco; Advisory/Consultancy: Nektar; Advisory/Consultancy: Boehringer-Ingelheim; Travel/Accommodation/Expenses: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.