Cutaneous adverse events: a predictor of tumour response under anti-PD-1 therapy for metastatic melanoma, a cohort analysis of 189 patients.

Abstract

Cutaneous adverse events (AEs) are the most prevalent toxicity under checkpoint inhibitors in clinical trials. In 'real-life' conditions of use, skin toxicities under anti-PD-1 have not been described to date in a large cohort. The objective of this study was to determine the clinical features of skin toxicities in patients with advanced melanoma receiving anti-PD-1 therapy under 'real-life' conditions of use. Secondary objectives were to evaluate the characteristics of patients with skin toxicities and to analyse associated extra-cutaneous toxicities, progression-free survival (PFS) and overall survival (OS). Advanced melanoma patients treated with nivolumab or pembrolizumab between August 2014 and October 2017 were included. Patients lost to follow-up or receiving anti-PD-1 as part of a clinical trial were excluded. One hundred and eighty-nine patients with metastatic melanoma (with 109 men (57.7%) were included. Cutaneous AE occurred in 39 patients (20.6%). The three most prevalent cutaneous AEs were skin eruption (macular-papular or eczematous) (n=18, 9.5%), vitiligo (n=16; 8.5%) and isolated pruritus (n=5, 2.6%). Grade 3-4 skin toxicity was diagnosed in five patients (2.6%). Atopy (28.2% vs. 12.0%; P=0.024), hypereosinophilia (20.5% vs. 8.7%; P=0.046), thyroiditis (17.9% vs. 4.7%; P=0.011) and renal toxicity (15.4% vs. 4%; P=0.019) were significantly associated with cutaneous AE. Patients with skin eruption (log-rank=0.001), vitiligo (log-rank=0.001) and any type of cutaneous AE (log-rank<0.001) had a better overall survival. Cutaneous AEs are frequent and often manageable toxicity and were a predictor of tumour response in melanoma patients under anti-PD-1 therapy in this cohort.