Efficacy and toxicity of BRAF targeted therapy in elderly patients with melanoma.
Authors: Stoff Ronen , Markovic Svetomir , McWilliams Robert R. , Kottschade Lisa A. , Montane Heather N. , Dimou Anastasios , Dudek Arkadiusz Z. , Yan Yiyi , Tan Winston , Dronca Roxana Stefania , Seetharam Mahesh , Chen Ruqin , Block Matthew Stephen 
Published: June 2024

e23270

Background: Melanoma is the most lethal form of skin cancer which have seen drastic improvement in patient survival over the last decade. BRAF is the most common driver mutation in melanoma, seen in ≈50% of all patients (≈30% of patients > 65). The use of BRAF & MEK inhibitors yields high response rates, though it is limited by toxicity and development of acquired resistance. Acknowledging these limitations, we aimed at assessing the efficacy and toxicity of these agents in melanoma patients > 65. Methods: We identified electronic medical records of all melanoma patients > 65 that were treated with BRAF & MEK inhibitors at our institution over the years 2017-2023. Data was retrospectively collected including demographics, disease characteristics, treatment given, response patterns and toxicity. Results: 106 patients were identified. The median age was 71 (65-89), 55% were males. The median follow up was 28.9 months. 32 (30%) patients were treated at first line, 58 (55%) at second line and 16 (15%) at third line. 88 (83%) evaluable patients received treatment for unresectable/metastatic disease of which 84% had an objective response (60% partial response, 24% complete response). Response rate (RR) was 82%, 85% and 87% for first, second and third line respectively. RR was 86% for patients with an increased serum lactate dehydrogenase. 33% of patients had active central nervous system (CNS) metastases at treatment initiation, for whom the systemic RR was 80% and the CNS RR was 39%. The median progression free survival (PFS) was 7.9 months, with a PFS of 6, 8.3 and 13.4 months for first, second and third line respectively. The median PFS was 5.7 months for patients with active CNS disease. The median overall survival (OS) from treatment initiation was 15.7 months (12.5, 14.5, 31.9 for first, second & third line respectively). The median OS for patients with CNS disease was 9.8 months. 16 patients were treated in the adjuvant setting, of which 6 (37%) finished treatment as planned, 3 stopped due to disease progression (19%) and 6 stopped due to toxicity (37%). 88% of patients experienced adverse events (AEs) of any grade, with 27% having grade 3-4 toxicity. There were no grade 5 toxicities reported. 36% of patients experienced one AE, while 52% experienced two or more. 21% of patients stopped treatment due to toxicity, 28% needed a dose reduction and 20% changed to different BRAF/MEK inhibitors. 10% of patients needed systemic corticosteroids to treat AEs. The most common toxicities seen were fever (30%), fatigue (30%), skin rash (22%), elevated liver function tests (20%), arthralgia/myalgia (15%), nausea (14%) and diarrhea (11%). 7% had decrease in cardiac ejection fraction with one grade 3 leading to treatment discontinuation. Conclusions: Treatment with BRAF & MEK inhibitors is challenging in older patients, with a high prevalence of toxicity leading to treatment modifications and discontinuation. Efficacy seems to be the same as in the general population.