Updated OS Data for the CA184-043 Trial: Immunotherapy with Ipilimumab Does Not Improve Survival in Patients with Metastatic Prostate Cancer
Ipilimumab is an approved immunotherapy that blocks the function of the immune checkpoint modulator CTLA-4 (cytotoxic T-lymphocyte antigen-4) to augment T-cell antitumor immune responses. The multicenter, randomized, double-blind, phase 3 clinical trial CA184-043 evaluated the efficacy of radiotherapy followed by ipilimumab or placebo in 799 men with advanced metastatic castration-resistant prostate cancer (mCRPC) who had at least 1 bone metastasis and had progressed with previous docetaxel therapy. It was previously reported that the primary end point of improvement in overall survival (OS) in patients with mCRPC was not met (hazard ratio [HR], 0.85; P = .053). At ESMO 2014, Fizazi and colleagues reported updated OS data for the CA184-043 trial with an additional 1 year of follow-up, which was conducted with the intent-to-treat population of patients with mCRPC in the CA184-043 trial (Fizazi K, et al. ESMO 2014: Abstract 763PD).
Consistent with the previous published report, the updated OS analysis showed no significant improvement in OS (HR, 0.84; P = .268) with ipilimumab plus radiotherapy compared with the control with an additional year of follow-up. The 2-year and 3-year OS rates for ipilimumab plus radiotherapy were 25% and 12%, respectively, compared with 17% and 6%, respectively, for radiotherapy alone. A post-hoc subgroup analysis showed that ipilimumab might benefit patients with favorable prognostic features, such as alkaline phosphatase <1.5 upper limit of normal, hemoglobin .11 g/dL, and no visceral metastasis (median OS, 22.1 vs 16.1; HR, 0.70).
As previously reported, immune-related adverse events included gastrointestinal, dermatologic, endocrine, and hepatic toxicities; however, the majority of the immune-related adverse events were manageable with established ipilimumab treatment algorithms.
With an additional 1 year of follow-up, ipilimumab plus radiotherapy did not improve survival outcomes in patients with advanced melanoma, with some preliminary evidence suggesting that specific subgroups might derive some benefit.