In contrast with a 3 mg/kg dose, ipilimumab monotherapy at a dose of 10 mg/kg is associated with improved overall survival, but a higher risk of treatment-related adverse events, among patients with metastatic melanoma, according to a study presented at the European Society for Medical Oncology (ESMO) 2016 Congress.1

Ipilimumab is a CTLA-4 inhibitor approved by the U.S. Food and Drug Administration for the treatment of unresectable or metastatic melanoma at a dose of 3 mg/kg every 3 weeks for 4 doses. Findings from a dose-ranging phase 2 study suggested, however, that the 10 mg/kg dose prolongs survival versus 3 mg/kg. Researchers therefore compared 3 mg/kg ipilimumab with 10 mg/kg in a phase 3 trial.

For the double-blind study (ClinicalTrials.gov Identifier: NCT01515189), investigators enrolled 727 treatment-naive or previously treated patients with unresectable stage III or IV melanoma who had not received prior therapy with BRAF or immune checkpoint inhibitors.

Participants were randomly assigned 1:1 to receive ipilimumab 3 mg/kg or 10 mg/kg intravenously every 3 weeks for 4 doses.

Median follow-up was about 43 months. Ipilimumab 10 mg/kg was associated with a median overall survival of 15.7 months (95% CI, 11.6-17.8) compared with 11.5 months (95% CI, 9.9-13.3) with 3 mg/kg, representing a 16% reduction in the risk of death with the 10 mg/kg dose (hazard ratio [HR], 0.84; 95% CI, 0.70-0.99; P = .04).

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Patients treated with the 10 mg/kg dose, however, reported higher rates of treatment-related grade 3 to 5 adverse events, grade 3 to 5 adverse events resulting in treatment discontinuation, and grade 3 to 5 immune-mediated adverse events.

Four patients in the 10 mg/kg arm died due to drug toxicity; 2 patients died from drug toxicity in the 3 mg/kg arm.

Reference

  1. Ascierto PA, Del Vecchio M, Robert C, et al. Overall survival (OS) and safety results from a phase 3 trial of ipilimumab (IPI) at 3 mg/kg vs 10 mg/kg in patients with metastatic melanoma. Paper presented at: European Society for Medical Oncology (ESMO) 2016 Congress; October 7-11, 2016; Copenhagen, Denmark.