Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma

J Clin Oncol. 2015 Jun 10;33(17):1889-94. doi: 10.1200/JCO.2014.56.2736. Epub 2015 Feb 9.

Abstract

Purpose: To provide a more precise estimate of long-term survival observed for ipilimumab-treated patients with advanced melanoma, we performed a pooled analysis of overall survival (OS) data from multiple studies.

Methods: The primary analysis pooled OS data for 1,861 patients from 10 prospective and two retrospective studies of ipilimumab, including two phase III trials. Patients were previously treated (n = 1,257) or treatment naive (n = 604), and the majority of patients received ipilimumab 3 mg/kg (n = 965) or 10 mg/kg (n = 706). We also conducted a secondary analysis of OS data (n = 4,846) with an additional 2,985 patients from an expanded access program. OS rates were estimated using the Kaplan-Meier method.

Results: Among 1,861 patients, median OS was 11.4 months (95% CI, 10.7 to 12.1 months), which included 254 patients with at least 3 years of survival follow-up. The survival curve began to plateau around year 3, with follow-up of up to 10 years. Three-year survival rates were 22%, 26%, and 20% for all patients, treatment-naive patients, and previously treated patients, respectively. Including data from the expanded access program, median OS was 9.5 months (95% CI, 9.0 to 10.0 months), with a plateau at 21% in the survival curve beginning around year 3.

Conclusion: To our knowledge, this is the largest analysis of OS to date for ipilimumab-treated patients with advanced melanoma. We observed a plateau in the survival curve, beginning at approximately 3 years, which was independent of prior therapy or ipilimumab dose. These data add to the evidence supporting the durability of long-term survival in ipilimumab-treated patients with advanced melanoma.

Trial registration: ClinicalTrials.gov NCT00032045 NCT00058279 NCT00077532 NCT00094653 NCT00135408 NCT00261365 NCT00289627 NCT00289640 NCT00324155 NCT00623766.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug Administration Schedule
  • Follow-Up Studies
  • Humans
  • Ipilimumab
  • Kaplan-Meier Estimate
  • Melanoma / drug therapy*
  • Melanoma / secondary
  • Prospective Studies
  • Retrospective Studies
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / pathology*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Ipilimumab

Associated data

  • ClinicalTrials.gov/NCT00032045
  • ClinicalTrials.gov/NCT00058279
  • ClinicalTrials.gov/NCT00077532
  • ClinicalTrials.gov/NCT00094653
  • ClinicalTrials.gov/NCT00135408
  • ClinicalTrials.gov/NCT00261365
  • ClinicalTrials.gov/NCT00289627
  • ClinicalTrials.gov/NCT00289640
  • ClinicalTrials.gov/NCT00324155
  • ClinicalTrials.gov/NCT00623766