Four-year survival rates for patients with metastatic melanoma who received ipilimumab in phase II clinical trials

Abstract

Background: This analysis was carried out to evaluate the long-term survival of patients with metastatic melanoma who received ipilimumab, a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte antigen-4, in clinical trials.

Patients and methods: Patients received ipilimumab in one of three completed phase II clinical trials (CA184-008, CA184-022, and CA184-007). Previously treated patients were enrolled in all studies, and treatment-naïve patients were also included in study CA184-007. Patients received ipilimumab at a dose of 10 mg/kg in studies CA184-008 and CA184-007, and at doses of 0.3, 3, or 10 mg/kg in study CA184-022. Ipilimumab was given every 3 weeks for four doses, and eligible patients could receive ipilimumab maintenance therapy every 12 weeks. In study CA184-022, patients could cross over to be retreated with ipilimumab at 10 mg/kg upon disease progression. Ongoing survival follow-up is conducted in a companion study, CA184-025.

Results: Four-year survival rates [95% confidence interval (95% CI)] for previously treated patients who received ipilimumab at 0.3, 3, or 10 mg/kg were 13.8% [6.1-22.5], 18.2% [9.5-27.6], and 19.7% [13.4-26.5] to 28.4% [13.9-44.2], respectively. In treatment-naïve patients who received ipilimumab at 10 mg/kg, 4-year survival rates were 37.7% [18.6-57.4] to 49.5% [23.8-75.4].

Conclusions: These results demonstrate durable survival in a significant proportion of patients with metastatic melanoma who received ipilimumab therapy.

Keywords: cytotoxic T-lymphocyte antigen-4; immunotherapy; ipilimumab; long-term survival; metastatic melanoma; survival rate.

Figure 1.

Treatment of patients included in the survival analyses. Patients in studies CA184-007, CA184-008, and CA184-022 could enroll in study CA184-025 for (i) retreatment with ipilimumab [10 mg/kg, every 3 weeks (Q3W) for 4 doses] if they experienced PD after an objective response or SD; (ii) ipilimumab maintenance therapy (Q12W) if they had an objective response or SD but had not progressed; (iii) survival follow-up only without further ipilimumab treatment if PD was their best overall response. In study CA184-022, patients treated with ipilimumab at 0.3 or 3 mg/kg could enroll at any time to receive ipilimumab retreatment. In groups 1 and 2, patients with PD could be reinduced with ipilimumab or followed up for survival if they experienced intolerable toxicity (Tox) or withdrew consent (WD).

Figure 2.

Kaplan–Meier estimates of overall survival. Analyses include all treated patients for study CA184-008 (A) and all randomized patients for studies CA184-022 (B) and CA184-007 (C). For study CA184-022 (B), 33% and 42% of patients in the 0.3 and 3 mg/kg dose groups, respectively, crossed over to the 10 mg/kg dose group. The vertical lines represent the current analyses of 4-year survival rates. Symbols indicate censored observations.