Background B-rapidly accelerated fibrosarcoma (BRAF) inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF-mutated melanoma patients. So far, the range of cutaneous adverse events has been characterized only for established BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (trametinib, cobimetinib).Objective The aim of this study was to investigate cutaneous adverse events emerging in melanoma patients treated with encorafenib and binimetinib.Methods Patients treated with BRAF and MEK inhibitors in clinical trials at the University Hospital of Zurich were identified. Frequency and features of cutaneous adverse events as well as their management were assessed based on the prospectively collected clinical and histopathological data. The events emerging during encorafenib and/or binimetinib therapy were compared to other BRAF and MEK inhibitors at the institution and in the literature. ResultsThe most frequent cutaneous adverse events observed in patients treated with encorafenib alone (n = 24) were palmoplantar hyperkeratosis (54%), palmoplantar erythrodysesthesia (58%) and alopecia (46%). Drug-induced papulopustular eruptions prevailed in patients with binimetinib monotherapy (n = 25). The most frequent cutaneous adverse events in patients treated with encorafenib/binimetinib (n = 49) were palmoplantar hyperkeratosis (10%).Conclusion Compared to data published for established BRAFi, encorafenib monotherapy showed less hyperproliferative cutaneous adverse events. In contrast, palmoplantar hyperkeratosis and palmoplantar erythrodysesthesia seem to occur more often. The combination of encorafenib and binimetinib is well tolerated and induces few cutaneous adverse events.

9590 Background: BRAF inhibitor (BRAFi) an MEK inhibitor (MEKi) monotherapies have shown to cause more cutaneous adverse events (cuAEs) in monotherapy compared to combination therapy. Encorafenib in combination with binimetinib showed improved PFS in patients with BRAF mutant melanoma (14.9 months). Furthermore, encorafenib showed superiority over vemurafenib. Objective: The aim of this study was to investigate cuAEs of melanoma patients treated with encorafenib and/or binimetinib and compare them to other BRAFi and MEKi induced cuAEs reported in the literature and observed in our control population. Methods: Patients treated with encorafenib, binimetinib, and other BRAFi/MEKi within approved clinical trials at the University Hospital of Zurich were collected and analyzed. Clinical and histological assessments were performed. Results: In 111 patients treated with BRAFi and/or MEKi, 212 related or possibly related cuAEs were identified. The percentage of patients with at least one cuAE is shown in the table below. The most frequent cuAEs observed in patients treated with encorafenib where palmoplantar hyperkeratosis (PPH, 50%), palmoplantar erythrodysesthesia (PPD, 53.8%) and alopecia (42.3%), whereas acanthopapillomas (83%), maculopapular exanthemas (63.3%), PPH and PPD (each 50%) prevailed in patients treated with vemurafenib. The most frequent observed cuAE in patients with dabrafenib/trametinib combination therapy were maculopapular exanthemas (18.2%) and erythema-annulare-like eruptions (18.2%), with encorafenib/binimetinib combination therapy PPH (10.6%) respectivly. Conclusions: Encorafenib showed less hyperproliferative cuAEs as previous BRAFi. However, PPH and PPD seem to occur more often compared to the literature of other BRAFi. Both is supporting the argument that encorafenib is a second generation BRAFi with a longer dissociation time. [Table: see text]