Chemotherapy efficacy in advanced melanoma patients after failure of immune checkpoint and BRAF/MEK inhibitors.

Introduction: Despite the introduction of new therapies for the treatment of advanced melanoma, treatment is ineffective for a certain number of patients. The efficacy of chemotherapy after failure of anti-programmed death receptor (PD-1) immunotherapy alone or combined with anti-cytotoxic T-lymphocyte-associated antigen (CTLA) is not fully understood. It is believed that due to the immunomodulatory effect of cytostatic agents, its efficacy may be greater when applied after the failure of immunotherapy. The aim of this study was to evaluate the efficacy of different chemotherapy regimens after failure of immunotherapy. Material and methods: Patients with advanced melanoma after failure of immunotherapy (anti-PD1+/- anti-CTLA-4) and BRAF mutation-targeted therapy with a BRAF/MEK inhibitor were included in a multicenter, retrospective analysis. Patients were treated with one of four chemotherapy regimens: dacarbazine (DTIC); paclitaxel with carboplatin; cisplatin, vinblastine and dacarbazine (CVD) or bleomycin, DTIC, lomustine, vincristine. The objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and overall survival (OS) were compared in study patients. Results: One hundred twenty-four patients were included in the study. Objective response rate was 16.88%, DCR was 38.96%, while median PFS and OS were 2.75 [95% CI: 2.25-3.5] and 6 months [95% CI: 4.75-40], respectively. There were no statistically significant differences in ORR, DCR, median PFS, and OS rates between the patients receiving different chemotherapy regimens. Conclusions: In advanced melanoma patients after failure of immune-checkpoint inhibitors with or without BRAF/MEK inhibitors, the choice of chemotherapy regimen remains dependent on the patient's general condition, comorbidities, the need for rapid reduction of tumor masses, and physician and patient preference.