Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials.

Background: Neoadjuvant ipilimumab plus nivolumab has yielded high response rates in patients with macroscopic stage III melanoma. These response rates translated to high short-term survival rates. However, data on long-term survival and disease recurrence are lacking.
Patients and Methods: In OpACIN, 20 patients with macroscopic stage III melanoma were randomized to ipilimumab 3 mg/kg plus nivolumab 1 mg/kg q3w four cycles of adjuvant or split two cycles of neoadjuvant and two adjuvant. In OpACIN-neo, 86 patients with macroscopic stage III melanoma were randomized to arm A (2× ipilimumab 3 mg/kg plus nivolumab 1 mg/kg q3w; n = 30), arm B (2× ipilimumab 1 mg/kg plus nivolumab 3 mg/kg q3w; n = 30), or arm C (2× ipilimumab 3 mg/kg q3w plus 2× nivolumab 3 mg/kg q2w; n = 26) followed by surgery.
Results: The median recurrence-free survival (RFS) and overall survival (OS) were not reached in either trial. After a median follow-up of 69 months for OpACIN, 1/7 patients with a pathologic response to neoadjuvant therapy had disease recurrence. The estimated 5-year RFS and OS rates for the neoadjuvant arm were 70% and 90% versus 60% and 70% for the adjuvant arm. After a median follow-up of 47 months for OpACIN-neo, the estimated 3-year RFS and OS rates were 82% and 92%, respectively. The estimated 3-year RFS rate for OpACIN-neo was 95% for patients with a pathologic response versus 37% for patients without a pathologic response (P < 0.001). In multiple regression analyses, pathologic response was the strongest predictor of disease recurrence. Of the 12 patients with distant disease recurrence after neoadjuvant therapy, 5 responded to subsequent anti-PD-1 and 8 to targeted therapy, although 7 patients showed progression after the initial response.
Conclusions: Updated data confirm the high survival rates after neoadjuvant combination checkpoint inhibition in macroscopic stage III melanoma, especially for patients with a pathologic response. Pathologic response is the strongest surrogate marker for long-term outcome.
Competing Interests: Disclosure AMM reports an advisory role for Bristol-Myers Squibb, MSD Oncology, Novartis, Pierre Fabre, QBiotics, and Roche. RPMS reports an advisory role for Merck Sharpe & Dohme, Novartis, and QBiotics; and was a speaker for Bristol-Myers Squibb. WJvH reports an advisory role for Amgen, Bristol-Myers Squibb, and Sanofi. BAvdW reports employment with Bristol-Myers Squibb. RAS reports an advisory role for Amgen, Bristol-Myers Squibb, Evaxion Biotech, GlaxoSmithKline, Merck Sharp & Dohme, Myriad Genetics, NeraCare GmbH, Novartis Australia, Novartis, Provectus Biopharmaceuticals Australia, QBiotics, and Roche; has received compensation for travel expenses from Bristol-Myers Squibb and Novartis Australia; has received honoraria from GlaxoSmithKline, Harvard Medical School, and Wake Forest School of Medicine; and has received research funding from the Australian National Health and Medical Research Council. JBAGH reports an advisory role for Achilles Therapeutics, BioNTech, Bristol-Myers Squibb, Immunocore, Instil Bio, Iovance Biotherapeutics, Ipsen, Molecular Partners, MSD Oncology, Neogene Therapeutics, Novartis, PokeAcell, Roche/Genentech, Sanofi, Third Rock Ventures, and T-Knife; has received research funding, paid to the institute, from Amgen, Asher Biotherapeutics, BioNTech, Bristol-Myers Squibb, MSD, Neon Therapeutics, and Novartis; and is stockowner of Neogene Therapeutics. TNS reports an advisory role for Allogene Therapeutics, Asher Bio, Celsius, Merus, Neogene Therapeutics, Scenic Biotech, and Third Rock Ventures; and is stockowner of Allogene Therapeutics, Asher Bio, Celsius, Merus, Neogene Therapeutics, Scenic Biotech, and Third Rock Ventures. ACJvA reports an advisory role for 4SC, Bristol-Myers Squibb, Amgen, Merck/Pfizer, Novartis, MSD Oncology, Pierre Fabre, Provectus, Sanofi, and Sirius Medical; and received research funding, all paid to the institute, from Amgen and Merck/Pfizer. GVL reports an advisory role for Agenus, Amgen, Array BioPharma, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Evaxion Biotech A/S, Hexal, Highlight Therapeutics, Innovent Biologics, Merck Sharp & Dohme, Novartis, OncoSec, PHMR Ltd, Pierre Fabre, Provectus Australia, QBiotics, and Regeneron; and has received honorarium from Bristol-Myers Squibb and Pierre Fabre. CUB reports research funding from Bristol-Myers Squibb, Novartis, and NanoString, all paid to the institute; has an advisory role for Bristol-Myers Squibb, MSD Oncology, Roche/Genentech, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, Genmab, Pierre Fabre, and Third Rock Ventures; and is stockowner of Uniti Cars and Immagene. All other authors have declared no conflicts of interest.
(Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)