Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial

J Clin Oncol. 2015 Apr 1;33(10):1191-6. doi: 10.1200/JCO.2014.56.6018. Epub 2015 Feb 23.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Diarrhea / chemically induced
  • Drug Administration Schedule
  • Exanthema / chemically induced
  • Female
  • Humans
  • Ipilimumab
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / drug therapy*
  • Melanoma / mortality
  • Middle Aged
  • Pruritus / chemically induced
  • Survival Analysis
  • Survival Rate
  • Time Factors
  • Treatment Outcome
  • Vitiligo / chemically induced

Substances

  • Antibodies, Monoclonal
  • Ipilimumab
  • Dacarbazine

Associated data

  • ClinicalTrials.gov/NCT00324155