Is there an overtreatment of melanoma patients at the end of their life? Results of a multicenter study on 193 melanoma patients.

BACKGROUND AND OBJECTIVES: There is a lack of data regarding the situation of melanoma patients receiving systemic therapies in their last months of life. PATIENTS AND METHODS: All melanoma patients who died in 2016 or 2017 and who had been treated by systemic therapies within the last three months of life were retrospectively analyzed. The study was conducted within the Committee "supportive therapy" of the Work Group Dermatological Oncology (ADO). RESULTS: 193 patients from four dermato-oncological centers were included. More than 60 % of the patients had ECOG ≥ 2 and most of them received immune checkpoint inhibitors (ICI) or targeted therapies (TT). 41 patients benefited from the last therapy in terms of radiological and laboratory findings or state of health. Although ECOG was worse in the TT cohort compared to the ICI group, the proportion of patients benefiting from the last therapy with TT was significantly higher and TT therapy could be carried out more often on an outpatient basis. CONCLUSIONS: This study indicates that there is a tendency towards an overtreatment at the end of life. Nevertheless, TT might be a reasonable therapeutic option for advanced BRAF mutant melanoma, even in highly palliative situations.

Discontinuation of BRAF/MEK-Directed Targeted Therapy after Complete Remission of Metastatic Melanoma-A Retrospective Multicenter ADOReg Study.

The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary real-world cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT.