Efficacy and safety of retreatment with ipilimumab in patients with pretreated advanced melanoma who progressed after initially achieving disease control

Clin Cancer Res. 2013 Apr 15;19(8):2232-9. doi: 10.1158/1078-0432.CCR-12-3080. Epub 2013 Feb 26.

Abstract

Purpose: Ipilimumab is a fully human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) that has been shown to improve survival in patients with pretreated, advanced melanoma in a phase III trial. Some patients in this study who initially responded to ipilimumab treatment but later progressed were eligible for retreatment with their original randomized regimen. Here, outcomes for these patients concerning baseline characteristics, best overall response, and disease control rate are assessed and considered with respect to the overall study population.

Experimental design: In the phase III study, 676 pretreated patients were randomly allocated to treatment with ipilimumab 3 mg/kg plus gp100 vaccine, ipilimumab 3 mg/kg plus placebo, or gp100 vaccine alone. Of these patients, 32 had a partial or complete objective response or stable disease after treatment and met the eligibility criteria for retreatment, although a total of 40 patients were retreated.

Results: Best overall response rates (complete responses plus partial responses) for 31 retreatment-eligible patients in the ipilimumab plus gp100 and ipilimumab plus placebo groups were 3 of 23 (13.0%) and 3 of 8 (37.5%), respectively, and disease control rates were 65.2% and 75.0%. No new types of toxicities occurred during retreatment and most events were mild-to-moderate.

Conclusion: Ipilimumab provided durable objective responses and/or stable disease in qualifying patients who received retreatment upon disease progression with a similar toxicity profile to that seen during their original treatment regimen.

Trial registration: ClinicalTrials.gov NCT00094653.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • CTLA-4 Antigen / immunology
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Combined Modality Therapy
  • Disease Progression
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Ipilimumab
  • Male
  • Melanoma / pathology
  • Melanoma / therapy*
  • Middle Aged
  • Retreatment
  • Retrospective Studies
  • Skin Diseases / chemically induced
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • CTLA-4 Antigen
  • Cancer Vaccines
  • Ipilimumab
  • gp100(209-2M) vaccine

Associated data

  • ClinicalTrials.gov/NCT00094653