Retrospective Analysis Of Safety In Elderly Braf V600 Mutation-Positive Advanced Melanoma Patients Treated With Dabrafenib (D) And Trametinib (T) And Correlation With Non-Elderly Patients

Melanoma in elderly patients has different features, and this population has higher risk of comorbidities. Efficacy and safety of D+T have been well established in 2 clinical phase III trials, however limited data has been reported for the elderly population. This study analyzes the real world care of patients with advanced melanoma treated with D+T in Spain, focused on the elderly population. We performed a retrospective descriptive analysis of elderly (≥75 years old, y.o.) and non-elderly (<75y.o.) BRAFV600+ advanced melanoma patients treated with D+T or D monotherapy in 10 Spanish academic centers. Clinical variables, safety, and efficacy of both groups were compared. Influence of variables on the initial dose and safety was analyzed by univariate and multivariate analysis. 159 patients were included, 130 <75y.o. and 29 ≥75y.o. Clinical features were similar between groups, except in number of comorbidities, number of metastatic sites, ECOG-PS, and BRAFV600 mutation type. 5 patients per group received D monotherapy (p=0.019) and this decision was only influenced by age. There were no differences in adverse events (AE) rate or grade between groups. However, pyrexia was more frequent in patients <75y.o. (42.3% vs 13.8%, p=0.005) while asthenia was more frequent in the elderly group (44.8% vs 25.4%, p=0.044). Besides, AE management was different: 83.5% of AEs in <75 y.o were treated without D or T modifications vs 64.5% in the elderly (p<0.001). Overall, ≥75y.o. patients had more D dose modifications (22.3 vs 41.4%, p=0.039), lower initial dose of T (p=0.005), more T interruptions (26.4 vs 50%; p=0.029) and less D and T dose intensity (p=0.018 and p=0.020). There were no differences in efficacy between groups, with a response rate, median progression-free survival and overall survival of 63.8%, 8.6 and 22.3 months in <75y.o. vs 62%, 10.3 and 29.1 months in ≥75 y.o. D+T is safe and effective in ≥75 y.o. patients with advanced BRAF600+ melanoma. AE management is different in this population compared to <75 y.o. patients. Differences in AE profile as the lower rate of pyrexia in elderly patients should be confirmed in future studies.