Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial
Michele Maio, Jean-Jacques Grob, Steinar Aamdal, Igor Bondarenko, Caroline Robert, Luc Thomas, Claus Garbe, Vanna Chiarion-Sileni, Alessandro Testori, Tai-Tsang Chen, Marina Tschaika, Jedd D Wolchok, Michele Maio, Jean-Jacques Grob, Steinar Aamdal, Igor Bondarenko, Caroline Robert, Luc Thomas, Claus Garbe, Vanna Chiarion-Sileni, Alessandro Testori, Tai-Tsang Chen, Marina Tschaika, Jedd D Wolchok
Abstract
Purpose: There is evidence from nonrandomized studies that a proportion of ipilimumab-treated patients with advanced melanoma experience long-term survival. To demonstrate a long-term survival benefit with ipilimumab, we evaluated the 5-year survival rates of patients treated in a randomized, controlled phase III trial.
Patients and methods: A milestone survival analysis was conducted to capture the 5-year survival rate of treatment-naive patients with advanced melanoma who received ipilimumab in a phase III trial. Patients were randomly assigned 1:1 to receive ipilimumab at 10 mg/kg plus dacarbazine (n = 250) or placebo plus dacarbazine (n = 252) at weeks 1, 4, 7, and 10 followed by dacarbazine alone every 3 weeks through week 22. Eligible patients could receive maintenance ipilimumab or placebo every 12 weeks beginning at week 24. A safety analysis was conducted on patients who survived at least 5 years and continued to receive ipilimumab as maintenance therapy.
Results: The 5-year survival rate was 18.2% (95% CI, 13.6% to 23.4%) for patients treated with ipilimumab plus dacarbazine versus 8.8% (95% CI, 5.7% to 12.8%) for patients treated with placebo plus dacarbazine (P = .002). A plateau in the survival curve began at approximately 3 years. In patients who survived at least 5 years and continued to receive ipilimumab, grade 3 or 4 immune-related adverse events were observed exclusively in the skin.
Conclusion: The additional survival benefit of ipilimumab plus dacarbazine is maintained with twice as many patients alive at 5 years compared with those who initially received placebo plus dacarbazine. These results demonstrate a durable survival benefit with ipilimumab in advanced melanoma.
Trial registration: ClinicalTrials.gov NCT00324155.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.
© 2015 by American Society of Clinical Oncology.
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Source: PubMed