1123P - Safety profile of nivolumab (NIVO) and ipilimumab (IPI) combination therapy in patients (pts) with advanced melanoma (MEL)

Abstract

Cumulative data indicate greater tumor response from the addition of IPI (anti-CTLA-4 antibody) to NIVO (anti-PD-1 antibody) in MEL pts, but with a higher frequency of adverse events (AEs) than observed with either agent alone. The objective of this pooled analysis is to describe the safety profile of NIVO + IPI across MEL studies in which established guidelines for AE management were utilized. A retrospective safety review was conducted for three phase 1-3 trials in which all MEL pts who received at least 1 dose of the standard regimen, NIVO 1 mg/kg + IPI 3 mg/kg Q3W x 4, then NIVO 3 mg/kg Q2W until disease progression or unacceptable toxicity. Analyses included AEs, select (immune-related) AEs, time to onset and resolution, use of immune-modulating agents (IMs) for management of toxicity, and effect of IMs on outcome. Among 448 pts, median age was 61 (range:18-87) and 25% had ECOG PS > 0. Median duration of follow-up was 13.2 months. Treatment-related grade 3–4 AEs occurred in 55% of pts, and led to discontinuation in 28%. The most frequent treatment-related select AEs of any grade were skin (64%) and gastrointestinal (47%); the most frequent grade 3–4 select AEs were hepatic (17%) and gastrointestinal (16%; Table). 30% developed a grade 2-4 select AE in >1 organ category. Median time to onset of grade 3–4 treatment-related select AEs ranged from 3.1 wks (skin) to 16.3 wks (renal). Excluding endocrine AEs, median time to resolution of grade 3–4 select AEs with IMs ranged from 1.1 wks (renal) to 7.3 wks (pulmonary). Resolution rates for non-endocrine grade 3–4 select AEs ranged between 79─100% using IMs. 4 (<1%) deaths were attributed to therapy. The frequency of grade 3–4 treatment-related AEs was higher with NIVO + IPI and time to onset of select AEs occurred earlier than with either agent alone. Resolution rates of select AEs were similar to those previously reported with IPI monotherapy.Tabled 1NIVO + IPI-treated pts (N = 448)Select AEs, %Any gradeGrade 3–4Skin647Rash354Pruritus352Gastrointestinal4716Diarrhea4410Colitis139Hepatic2917Alanine aminotransferase increased189Aspartate aminotransferase increased176Hepatitis22Endocrine305Hypophysitis92 Open table in a new tab