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

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.

Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma

“…8 In a pooled analysis of patients with advanced melanoma, treatment with single-agent ipilimumab produced a median OS of 11.4 months. 23 In CheckMate 067, objective response to ipilimumab in patients with advanced melanoma was 19%. 24 …”

Targeted agents and immunotherapies: optimizing outcomes in melanoma

“…A consistent observation throughout the clinical trials of anti-CTLA-4 antibodies was that a proportion of patients had long-term survival independent of the extent of response. In a pooled-analysis of 1,861 patients who had participated in the phase II and III clinical trials of ipilimumab 82 , 22% were alive at 3 years and a plateau on the survival curve suggested the likelihood of longerterm survival thereafter. A clinical point of interest surrounding ipilimumab and other checkpoint-inhibitor immunotherapies relates to the use of concomitant steroid administration.…”

“…Substantial evidence has established the benefit of BRAF-inhibitor-based therapy, at least in the short term, for most patients with BRAF-V600-mutant melanoma, whereas ~20% and ~35% of patients with an objective or stable-disease response to ipilimumab 82 and nivolumab 86 or pembrolizumab 103 , respectively, maintain disease control for many years (up to 5 years based on the most up-to-date follow-up data). Thus, from a clinical perspective alone, the potential role of combination regimens containing molecularly targeted and immuno therapies is of considerable interest.…”

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

“…However, as novel agents extend patient survival times, it becomes increasingly difficult to conduct long clinical trials in order to measure OS [75,76]. Although the use of ICBs has improved survival in melanoma over standard chemotherapy, with some patients experiencing OS of 3 to 5 years [77,78], when the follow-up is less than 1 year, median OS is usually not reached [22,23,39,43]. Therefore, there is an interest in validating surrogate endpoints that can accurately predict survival benefit in clinical trials of immunotherapy and using these surrogate endpoints for drug approval [75].…”