Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies

Abstract

Background: This report provides a survival update at a follow-up of >5 years (5.5-6 years) for patients with advanced melanoma who previously received ipilimumab in phase II clinical trials. Safety and efficacy data following ipilimumab retreatment are also reported.

Patients and methods: Patients who previously received ipilimumab 0.3, 3, or 10 mg/kg in one of six phase II trials (CA184-004, CA184-007, CA184-008, CA184-022, MDX010-08, and MDX010-15) were eligible to enroll in the companion study, CA184-025. Upon enrollment, patients initially received ipilimumab retreatment, extended maintenance therapy, or were followed for survival only. Overall survival (OS) rates were evaluated in patients from studies CA184-004, CA184-007, CA184-008, and CA184-022. Safety and best overall response during ipilimumab retreatment at 10 mg/kg were assessed in study CA184-025.

Results: Five-year OS rates for previously treated patients who received ipilimumab induction at 0.3, 3, or 10 mg/kg were 12.3%, 12.3%-16.5%, and 15.5%-28.4%, respectively. Five-year OS rates for treatment-naive patients who received ipilimumab induction at 3 or 10 mg/kg were 26.8% and 21.4%-49.5%, respectively. Little to no change in OS was observed from year 5 up to year 6. The objective response rate among retreated patients was 23%. Grade 3/4 immune-related adverse events occurred in 25%, 5.9%, and 13.2% of retreated patients who initially received ipilimumab 0.3, 3, and 10 mg/kg, with the most common being observed in the skin (4.2%, 2.9%, 3.8%) and gastrointestinal tract (12.5%, 2.9%, 3.8%), respectively.

Conclusions: At a follow-up of 5-6 years, ipilimumab continues to demonstrate durable, long-term survival in a proportion of patients with advanced melanoma. In some patients, ipilimumab retreatment can re-establish disease control with a safety profile that is comparable with that observed during ipilimumab induction. Further studies are needed to determine the contribution of ipilimumab retreatment to OS.

Clinicaltrialsgov: NCT00162123.

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

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1.

Flow diagram for patients from phase II parent trials who enrolled in the companion study CA184-025. Upon enrollment in study CA184-025, patients received ipilimumab retreatment (cohort 1) or extended maintenance therapy (cohort 2), or were followed for survival only (cohort 3). aFive patients did not meet study criteria, and one patient failed screening for other reasons. bInduction dose received in the parent trial. MD, multidose; SD, single dose.

Figure 2.

Kaplan–Meier estimates of overall survival for studies: CA184-004 (A), CA184-007 (B), CA184-008 (C), and CA184-022 (D). Analyses for study CA184-008 include all treated patients, whereas those for studies CA184-004, CA184-007, and CA184-022 include all randomized patients.

Figure 2.

Kaplan–Meier estimates of overall survival for studies: CA184-004 (A), CA184-007 (B), CA184-008 (C), and CA184-022 (D). Analyses for study CA184-008 include all treated patients, whereas those for studies CA184-004, CA184-007, and CA184-022 include all randomized patients.