The activity of pembrolizumab in therapy of pretreated metastatic melanomas — two centres’ experience

Abstract

Introduction. Pembrolizumab [programmed death 1 (PD-1) checkpoint inhibitor] mediates durable responses and prolongs survival in patients with advanced melanomas. We assessed the efficacy and safety of pembrolizumab in pretreated metastatic melanoma patients outside clinical trials. Methods. Fifty-four patients (median age 57 years; range 18–77) after progression on previous therapy (at least ipilimumab) in metastatic setting were administered pembrolizumab at a registered dose 2 mg/kg every three weeks and were observed for progression-free survival (PFS), overall survival (OS), responses, and toxicity. Median follow-up time for survivors was 8.5 months. Results. In all except six cases pembrolizumab was given in at least third line of systemic therapy. All patients (except two patients with ocular melanomas) had cutaneous origin of the primary; 16 were BRAF -positive (30%), 42 patients were in M1c stage (78%); and 27 patients had increased initial LDH level (50%). The clinical benefit of pembrolizumab therapy was 50% with one complete remission, seven partial remissions, and 19 stable diseases. Thirty-six patients received more than four doses of the drug; 13 patients still remain on treatment. Median OS was not reached. The estimated one-year OS was 48%. We observed no differences in OS between BRAF -positive and BRAF -negative cases. Poorer OS was found in patients with initially increased LDH level (p = 0.04), and slightly worse results were seen for patients treated with more than three lines of therapy and in M1c stage. Median PFS was 5.6 months, estimated one-year PFS rate was 40%, and better PFS was observed for patients with initially normal LDH (7.5 vs . 4.5 months; p = 0.02). The treatment was well tolerated with adverse events (AE) occurring in 14 patients (26%), but in only three cases grade 3 AEs were observed (6%): diarrhoea, diabetes mellitus, pneumonitis. Conclusions. Pembrolizumab confirmed its activity and safety outside clinical trials in therapy of pretreated metastatic melanomas. Anti-PD-1 inhibitors are the preferred treatment option in advanced melanoma management.