Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma
Paolo A. Ascierto, Michele Del Vecchio, Andrzej Maćkiewicz, Caroline Robert, Vanna Chiarion‐Sileni, Ana Arance, Célèste Lebbé, Inge Marie Svane, Catriona M. McNeil, Piotr Rutkowski, Carmen Loquai, Laurent Mortier, Omid Hamid, Lars Bastholt, Brigitte Dréno, Dirk Schadendorf, Claus Garbe, Marta Nyakas, Jean-Jacques Grob, L. Thomas, Gabriella Liszkay, Michael Smylie, Christoph Höeller, Virginia Ferraresi, Florent Grange, Ralf Gutzmer, Joanna Pikiel, Fareeda Hosein, Burçin Şimşek, Michele Maio
Abstract
Background We have previously reported significantly longer overall survival (OS) with ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with advanced melanoma, with higher incidences of adverse events (AEs) at 10 mg/kg. This follow-up analysis reports a 5-year update of OS and safety. Methods This randomized, multicenter, double-blind, phase III trial included patients with untreated or previously treated unresectable stage III or IV melanoma. Patients were randomly assigned (1:1) to ipilimumab 10 mg/kg or 3 mg/kg every 3 weeks for 4 doses. The primary end point was OS. Results At a minimum follow-up of 61 months, median OS was 15.7 months (95% CI 11.6 to 17.8) at 10 mg/kg and 11.5 months (95% CI 9.9 to 13.3) at 3 mg/kg (HR 0.84, 95% CI 0.71 to 0.99; p=0.04). In a subgroup analysis, median OS of patients with asymptomatic brain metastasis was 7.0 months (95% CI 4.0 to 12.8) in the 10 mg/kg group and 5.7 months (95% CI 4.2 to 7.0) in the 3 mg/kg group. In patients with wild-type or mutant BRAF tumors, median OS was 13.8 months (95% CI 10.2 to 17.0) and 33.2 months (95% CI 19.4 to 45.2) in the 10 mg/kg group, and 11.2 months (95% CI 9.2 to 13.8) and 19.7 months (95% CI 11.6 to 25.3) in the 3 mg/kg group, respectively. The incidence of grade 3/4 treatment-related AEs was 36% in the 10 mg/kg group vs 20% in the 3 mg/kg group, and deaths due to treatment-related AEs occurred in four (1%) and two patients (1%), respectively. Conclusions This 61-month follow-up of a phase III trial showed sustained long-term survival in patients with advanced melanoma who started metastatic treatment with ipilimumab monotherapy, and confirmed the significant benefit for those who received ipilimumab 10 mg/kg vs 3 mg/kg. These results suggest the emergence of a plateau in the OS curve, consistent with previous ipilimumab studies. Trial registration number NCT01515189 .