Nivolumab for Resected Stage III or IV Melanoma 9 Years

Author(s): Paolo A. Ascierto, M.D.1; Michele Del Vecchio, M.D.2; Barbara Merelli, M.D.3; Helen Gogas, M.D., Ph.D.4; Ana M. Arance, M.D., Ph.D.5; Stéphane Dalle, M.D., Ph.D.6; Charles Lance Cowey, M.D., M.P.H.7; Michael Schenker, M.D.8,9; Caroline Gaudy-Marqueste, M.D., Ph.D.10; Jacopo Pigozzo, M.D.11; Iván Márquez-Rodas, M.D., Ph.D.12; Marcus O. Butler, M.D.13,14; Anna Maria Di Giacomo, M.D., Ph.D.15; Oleg Gligich, M.D.16; Luis De La Cruz-Merino, M.D.17,18; Petr Arenberger, M.D., Ph.D.19,20; Victoria Atkinson, M.D.21,22; Paul Nathan, M.D.23; Andrew Hill, F.R.A.C.P.24; Michael Millward, M.D.25,26; Leslie A. Fecher, M.D.27; Nikhil I. Khushalani, M.D.28; Paola Queirolo, M.D.29; Raheela Soomro, M.D.30; Dhanrajsinh Rathod, M.S.30; Margarita Askelson, M.S.30; Melanie Pe Benito, M.Sc.30; Devanand Joseph, M.Sc.30; James Larkin, F.R.C.P., Ph.D.31;
Source: DOI: 10.1056/NEJMoa2504966
Original Article
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Dr. Anjan Patel's Thoughts

The 9-year CheckMate 238 data show that adjuvant Nivo maintains a significant recurrent-free survival (RFS) advantage over the International Prognostic Index (Ipi) (median 61.1 vs 24.2 months; 9-year RFS 44% vs 37%) without a statistically significant overall survival (OS) difference (69% vs 65% at 9 years). OS is similar but I think this may highlight the shift towards neoadjuvant immunotherapy (IO) and effective salvage therapies.

BACKGROUND

In the CheckMate 238 trial, patients with resected stage IIIB–C or stage IV melanoma who were treated with nivolumab had longer recurrence-free survival than those who received ipilimumab. Data were needed on longer-term survival.

METHODS

We randomly assigned patients in a 1:1 ratio to receive an intravenous infusion of nivolumab ( a dose of 3 mg per kilogram of body weight every 2 weeks) or ipilimumab ( a dose of 10 mg per kilogram every 3 weeks for four doses, then every 12 weeks) for up to 1 year or until disease recurrence or the occurrence of unacceptable toxic effects. Randomization was stratified according to disease stage and status with respect to programmed cell death ligand 1. The primary end point was recurrence-free survival; secondary end points included overall and distant metastasis–free survival and safety. Research Summary Nivolumab for Resected Stage III or IV Melanoma 9 Years

RESULTS

a minimum follow-up of nearly 9 years (107 months), the median duration of recurrence-free survival was 61.1 months with nivolumab and 24.2 months with ipilimumab (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.63 to 0.90); 9-year recurrence-free survival was 44% and 37%, respectively. The median duration of distant metastasis–free survival in patients with stage III melanoma was more than 9 years with nivolumab and 83.8 months with ipilimumab, with 9-year survival of 54% and 48%, respectively (hazard ratio for distant metastasis or death, 0.81; 95% CI, 0.65 to 1.00). The median overall survival was more than 9 years in both trial groups, with 9-year survival of 69% in the nivolumab group and 65% in the ipilimumab group (hazard ratio for death, 0.88; 95.03% CI, 0.69 to 1.11). The rates of death from melanoma 9 years were 26% with nivolumab and 30% with ipilimumab (hazard ratio, 0.87; 95% CI, 0.67 to 1.13). Subsequent systemic therapy was administered to fewer patients in the nivolumab group than in the ipilimumab group (37.3% vs. 44.6%). No new late adverse events were reported.

CONCLUSIONS

The 9-year final data support a sustained finding of longer recurrence-free survival with nivolumab than with ipilimumab. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906; Eudra-CT number, 2014-002351-26.)

Author Affiliations

1Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 2Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; 3Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII Bergamo, Bergamo, Italy; 4National and Kapodistrian University of Athens, Athens; 5Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona; 6Hospices Civils de Lyon, Pierre-Bénite, France; 7Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas; 8Oncology Center SF Nectarie, Craiova, Romania; 9University of Medicine and Pharmacy, Craiova, Romania; 10Aix-Marseille University, Assistance Publique–Hôpitaux de Marseille, Timone Hospital, Marseille, France; 11Instituto Oncologico Veneto–IRCCS, Padua, Italy; 12Hospital General Universitario Gregorio Marañón, Madrid; 13Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto; 14Department of Immunology, Princess Margaret Cancer Centre, University of Toronto, Toronto; 15University of Siena and Center for Immuno-Oncology, University Hospital, Siena, Italy; 16Mount Sinai Comprehensive Cancer Center, Miami Beach, FL; 17Cancer Immunotherapy, Biomedicine Institute of Seville–Consejo Superior de Investigaciones Científicas, Department of Clinical Oncology, University Hospital Virgen Macarena, Seville, Spain; 18School of Medicine, University of Seville, Seville, Spain; 19Charles University Third Faculty of Medicine, Prague, Czech Republic; 20University Hospital Královské Vinohrady, Prague, Czech Republic; 21Gallipoli Medical Research Foundation, Brisbane, QLD, Australia; 22Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia; 23Mount Vernon Cancer Centre, Northwood, United Kingdom; 24Tasman Health Care, Southport, QLD, Australia; 25University of Western Australia, Nedlands, Australia; 26Sir Charles Gairdner Hospital, Nedlands, WA, Australia; 27University of Michigan Rogel Cancer Center, Ann Arbor; 28Moffitt Cancer Center and Research Institute, Tampa, FL; 29European Institute of Oncology, IRCCS, Milan; 30Bristol Myers Squibb, Princeton, NJ; 31Royal Marsden Hospital, London

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