Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma

Robert, Caroline and Thomas, Luc and Bondarenko, Igor and O’Day, Steven and Weber, Jeffrey and Garbe, Claus and Lebbe, Celeste and Baurain, Jean-François and Testori, Alessandro and Grob, Jean-Jacques and Davidson, Neville and Richards, Jon and Maio, Michele and Hauschild, Axel and Miller, Wilson H. and Gascon, Pere and Lotem, Michal and Harmankaya, Kaan and Ibrahim, Ramy and Francis, Stephen and Chen, Tai-Tsang and Humphrey, Rachel and Hoos, Axel and Wolchok, Jedd D. (2011) Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma. The New England Journal of Medicine = N Engl J Med, 364. pp. 2517-2526. ISSN 0028-4793 (print); 1533-4406 (online)

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Background Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma. Methods We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no doselimiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was overall survival. Results Overall survival was significantly longer in the group receiving ipilimumab plus dacarbazine than in the group receiving dacarbazine plus placebo (11.2 months vs. 9.1 months, with higher survival rates in the ipilimumab–dacarbazine group at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%), and 3 years (20.8% vs. 12.2%) (hazard ratio for death, 0.72; P<0.001). Grade 3 or 4 adverse events occurred in 56.3% of patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated with dacarbazine and placebo (P<0.001). No drug-related deaths or gastrointestinal perforations occurred in the ipilimumab–dacarbazine group. Conclusions Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma. The types of adverse events were consistent with those seen in prior studies of ipilimumab; however, the rates of elevated liver-function values were higher and the rates of gastrointestinal events were lower than expected on the basis of prior studies. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00324155.)

Item Type: Article
Additional Information: https://www.nejm.org/doi/full/10.1056/NEJMoa1104621
Subjects: Oncology
Divisions: Departments > Department of Oncology and Medical Radiology
Depositing User: Елена Шрамко
Date Deposited: 28 Dec 2021 13:20
Last Modified: 28 Dec 2021 13:20
URI: http://repo.dma.dp.ua/id/eprint/7270

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