Real-world effectiveness and safety of dabrafenib-trametinib as first-line of treatment for BRAF mutated metastatic melanoma: Results of the study GEM1801.

e21515 Background: Dabrafenib-Trametinib (DT) is included in the therapeutic arsenal for BRAFV600-mutant metastatic melanoma. However, detailed effectiveness results for dabrafenib and trametinib depending on patient prognostic profile in the real-world are limited. Methods: GEM1801 is a prospective observational study that analyzes the clinical and pathological disease presentation patterns, the different lines of treatment choices and the health outcomes derived from treatments in patients with melanoma in Spain. Here we focus on patients receiving DT as first-line treatment in the metastatic melanoma. Based on previous studies, we defined 3 subgroups: good prognosis (normal LDH and < 3 metastatic sites), poor prognosis (high LDH and ≥3 metastatic sites), and intermediate prognosis (neither of good or poor prognosis). Results: From August 2018 to December 2022, 140 patients receiving DT were enrolled; 45 (32.1%) with good, 42 (30%) with intermediate and 34 (24.3%) with poor prognosis. Subgroup allocation was not possible for 19 patients due to missing info on LDH or metastatic sites. Overall survival (OS) was longer in patients with good versus poor prognosis (median 26.2 vs 10 months; p = 0.024), while those with intermediate prognosis showed a mixed profile with a median OS of 17.4 months. Response to treatment also showed correlation with OS (3-years OS rate: 57.1% vs 23% vs 46.9% vs 26.8% for CR, PR, SD and PD, respectively; p < 0.001). In patients who had a complete response, the 5-year OS rate was 58.3% (95% CI: 31.3-100) while the median overall survival was not reached. In patients with intermediate prognosis, the ECOG-PS was the main prognostic factor in multivariate analysis (hazard ratio: 4.6; 95% CI: 1.8-1.7; p = 0.002). The reported grade 3-5 toxicity was less than 5%. Treatment-related adverse events were reported in 5 (3.6%) patients, consisting of fever, mucositis, pneumonitis, neutropenia, ocular toxicity and retinal detachment. There were no differences across prognostic subgroups ( p = 0.741). Conclusions: DT in the Real-World has an acceptable effectiveness and safety profile. Prognostic groups could help in the selection of patients who could achieve a complete response, since it is the most important prognostic biomarker. Clinical trial information: NCT03605771 . [Table: see text]