Results from CheckMate 067 have shown significant improvements in objective response, progression-free survival (PFS), and overall survival (OS) with NIVO+IPI and NIVO alone vs IPI in patients with advanced treatment-naive melanoma. Here we present 5-year outcomes from the study.
Eligible patients with previously untreated stage III or IV melanoma (N = 945) were randomly assigned 1:1:1 and stratified by programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. Patients received NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W followed by NIVO 3 mg/kg Q2W (n = 314), NIVO 3 mg/kg Q2W + placebo (n = 316), or IPI 3 mg/kg Q3W for 4 doses + placebo (n = 315) until progression or unacceptable toxicity. Co-primary endpoints were OS and PFS; the study was not powered to compare the NIVO-containing groups. Descriptive analyses were performed to evaluate efficacy between NIVO+IPI and NIVO, treatment-free status, and health-related quality of life (HRQoL).
With a minimum follow-up of 60 months, the NIVO-containing arms continued to show improved OS, PFS, and response vs IPI (table). In addition, descriptive analyses showed longer OS with NIVO+IPI (median OS, > 60.0 mo [not reached]) than with NIVO alone (median OS, 36.9 mo), as well as a higher proportion of patients alive and treatment-free with the combination. No sustained deterioration of HRQoL (EQ-5D-3L utility index) was observed during treatment or following treatment discontinuation with NIVO or NIVO+IPI. LBA68_PR NR, not reached. Although a median was reported at the previous analysis, that estimate was immature and greater than the minimum study follow-up. > 60.0 mo.NIVO+IPI NIVO IPI (n = 314) (n = 316) (n = 315) Objective response rate, % (95% CI) 58 (53–64) 45 (39–50) 19 (15–24) Median duration of response, mo (95% CI) NRa NR (50.4–NR) 14.4 (8.3–53.6) Median PFS, mo (95% CI) 11.5 (8.7–19.3) 6.9 (5.1–10.2) 2.9 (2.8–3.2) 5-year PFS rate, % (95% CI) 36 (31–42) 29 (24–35) 8 (5–12) Median OS, mo (95% CI) NRb (38.2–NR) 36.9 (28.2–58.7) 19.9 (16.8–24.6) 5-year OS rate, % (95% CI) 52 (46–57) 44 (39–50) 26 (22–31) BRAF mutant 60 (50–69) 46 (36–56) 30 (21–39) BRAF wild-type 48 (41–54) 43 (37–50) 25 (19–31) PD-L1 < 5% 51 (44–57) 43 (36–50) 24 (18–30) PD-L1 ≥ 5% 57 (44–68) 51 (40–62) 33 (23–44) Median time from randomization to subsequent systemic therapy, mo (95% CI) NR (59.6–NR) 25.2 (16.0–43.2) 8.0 (6.5–8.7) Patients alive and free from subsequent therapy, n/N (%) 112/151 (74) 75/130 (58) 30/67 (45)
This 5-year analysis represents the longest phase III follow-up for checkpoint inhibitor combination therapy and demonstrates long-term survival with both NIVO-containing arms vs IPI. In descriptive analyses, NIVO+IPI was associated with improved survival and a higher likelihood of being alive and treatment-free compared with NIVO alone, both without loss of QoL.
NCT01844505.
Writing and editorial assistance was provided by Melissa Kirk, PhD, and Michele Salernitano of StemScientific, an Ashfield Company.
Bristol-Myers Squibb.
Bristol-Myers Squibb.
J.M.G. Larkin: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Achilles; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boston Biomedical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): BMS; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: EUSA Pharma; Honoraria (self), Advisory / Consultancy: GSK; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Imugene; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy: iOnctura; Honoraria (self), Advisory / Consultancy: Kymab; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Nektar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Secarna; Research grant / Funding (self): Aveo; Research grant / Funding (self): Covance; Honoraria (self), Advisory / Consultancy: Vitaccess. V. Chiarion-Sileni: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck-Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Incyte. R. Gonzalez: Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): Genentech/Roche; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): GSK; Honoraria (self), Research grant / Funding (self): Array; Honoraria (self), Research grant / Funding (self): Amgen; Honoraria (self), Research grant / Funding (self): Incyte; Honoraria (self), Research grant / Funding (self): NewLink Genetics; Research grant / Funding (self): Merck; Research grant / Funding (self): Takeda; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Checkmate Pharmaceuticals; Research grant / Funding (self): Tesaro; Research grant / Funding (self): Syndax; Research grant / Funding (self): Nektar. J.J. Grob: Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Roche/Genentech; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: AMGEN; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Sun Pharma. P. Rutkowski: Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): Blueprint Medicines . C. Lao: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Dynavax; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Immunocore. D. Schadendorf: Honoraria (self): Roche/Genentech; Honoraria (self): Merck Serono; Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis, Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Immunocore, Philogen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Incyte, Regeneron; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: 4SC, Mologen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Mologen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Sanofi/Regeneron; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Sysmex; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Grünenthal Group; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Agenus; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Array; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BioPharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: LEO Pharma. J. Wagstaff: Honoraria (self): Bristol-Myers Squib . R. Dummer: Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Sun Pharma; Advisory / Consultancy: Sanofi; Honoraria (self): Amgen; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre; Honoraria (self): Roche; Honoraria (self): Sun Pharma; Honoraria (self): Takeda; Honoraria (self): Sanofi. P.F. Ferrucci: Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre. M. Smylie: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck; Honoraria (self): Sanofi Genzyme; Honoraria (self): Novartis. D. Hogg: Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): EMD Sereno; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): Merck. I. Marquez-Rodas: Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (self): BIONCOTECH; Honoraria (self), Research grant / Funding (self): AMGEN; Honoraria (self), Research grant / Funding (self): Incyte; Honoraria (self): Sanofi ; Honoraria (self): Regeneron. J.B.A.G. Haanen: Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Novartis; Research grant / Funding (self): MSD; Research grant / Funding (self): Neon Therapeutics . J. Rizzo: Honoraria (self), Full / Part-time employment: Bristol-Myers Squibb. A. Balogh: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. F..S. Hodi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): Merck, EMD Serono, Takeda, Surface, ; Honoraria (self): Genentech/Roche, Compass Therapeutics,; Honoraria (self): Apricity, Bayer, Aduro, Partners Therapeutics; Honoraria (self): Sanofi, Pfizer, Pionyr, Verastem; Honoraria (self): Rheos, Kairos, Bicara; Honoraria (self), Research grant / Funding (self): Novartis; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Torque, 7 Hills Pharma, Psioxus Therapeutics ; Licensing / Royalties: patent Methods for Treating MICA-Related Disorders (#20100111973) with royalties paid; a patent Tumor Antigens and Uses Thereof (#7250291) issued; a patent Angiopoiten-2 Biomarkers Predictive of Anti-Immune Checkpoint Response (#20170248603) pending; a . J. Wolchok: Patent information: Xenogeneic DNA Vaccines; Alphavirus Replicon Particles Expressing TRP2; Myeloid-derived Suppressor cell (MDSC) assay; Newcastle Disease Viruses for Cancer Therapy; Genomic Signature to Identify Responders to Ipilimumab in Melanoma; Engineered Vaccinia Viruses for Cancer Immunotherapy; Anti-CD40 agonist mAb fused to Monophosphoryl Lipid A (MPL) for cancer therapy; CAR+ T cells targeting differentiation antigens as means to treat cancer; Anti-PD1 Antibody; Anti-CTLA4 antibodies; Anti-GITR antibodies and methods of use thereof; Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb ; Honoraria (self): Advaxis, Elucida, Amgen, Eli Lilly; Honoraria (self): Apricity, F Star, Array BioPharma, Imvaq; Honoraria (self): Ascentage, Janssen, Astellas, Kleo; Honoraria (self): Bayer, Merck, Adaptive Biotech, Neon Therapeutics; Honoraria (self): Beigene, ONO, Celgene, Polaris Pharma; Honoraria (self): Chugai, Polynoma, PsiOxus, Puretech; Honoraria (self): Recepta, Sellas Life Sciences; Honoraria (self): Serametrix, Surface, Syndax; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Potenza Therapeutics, Tizona Pharma; Honoraria (self), Research grant / Funding (self): Genentech, MedImmune; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Trieza, Linneaus. All other authors have declared no conflicts of interest.