Survival for patients discontinuing nivolumab plus ipilimumab

June 16, 2016

Abstract

Background
Results from CheckMate 069 demonstrated a significant improvement in objective response rate (ORR) and progression-free survival (PFS) with NIVO+IPI vs IPI alone in treatment-naïve patients (pts) with BRAF wild-type MEL (N Engl J Med2015;372:2006). We evaluated overall survival (OS) in pts who discontinued treatment due to toxicity in this study. 

Methods
Pts (N = 142) were randomized 2:1 to receive NIVO 1 mg/kg plus IPI 3 mg/kg or IPI 3 mg/kg plus placebo every 3 weeks x 4 doses, followed by NIVO 3 mg/kg or placebo, respectively, every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was ORR in pts with BRAF wild-type tumors. Secondary and exploratory endpoints included PFS and OS. A post-hoc analysis was performed to evaluate OS in pts who discontinued treatment due to toxicity. 

Results
At a follow-up of 18 months, median OS in pts who discontinued treatment was not reached with NIVO+IPI and was 11.2 months for IPI alone (Table). Similar 18-month OS rates were observed in pts who discontinued NIVO+IPI due to toxicity and in the overall treatment group (Table). Among pts who discontinued NIVO+IPI, ORR was 68% (27% achieved a complete response). Median duration of response was not reached and 21 of 30 pts (70%) remain in response. Grade 3/4 treatment-related adverse events (AEs) occurred in 55% of pts in the NIVO+IPI group vs 22% with IPI, and led to discontinuation in 30% and 9% of pts, respectively. In pts who discontinued NIVO+IPI due to toxicity, resolution rates of treatment-related select AEs ranged from 89% to 100% (40% for endocrine AEs). Efficacy updates, including 2-year OS rates, will be presented for these pts. 

Conclusions
These data suggest that pts who discontinue NIVO+IPI treatment due to drug toxicity derive an OS benefit similar to that observed in the overall population.

Source:

Hodi, FS, et al. Overall survival in patients with advanced melanoma (MEL) who discontinued treatment with nivolumab (NIVO) plus ipilimumab (IPI) due to toxicity in a phase II trial (CheckMate 069).  Journal of Clinical Oncology, 2016 ASCO Annual Meeting (June 3-7, 2016). Vol 34, No 15 suppl (May 20 Supplement), 2016: 9518 © 2016 American Society of Clinical Oncology
http://meeting.ascopubs.org/cg...