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Analysis of efficiency and tolerance of triple BRAF inhibitor/MEK inhibitor/anti-PD1 combined therapy in patients with melanoma central nervous system metastases occurring during first-line BRAFinh/MEKinh therapy
Mémoire de Master / Thèse d'exercice   Open Access

Analysis of efficiency and tolerance of triple BRAF inhibitor/MEK inhibitor/anti-PD1 combined therapy in patients with melanoma central nervous system metastases occurring during first-line BRAFinh/MEKinh therapy

Marie Fabre
Masters , Université de Montpellier
06/10/2022

Résumé

CNS metastases Tritherapy Targeted therapy Métastases du SNC Trithérapie Thérapie ciblée Melanoma Immunotherapy Mélanome Immunothérapie
Background and purpose: eventhough new systemic therapies significantly improved objective response rate (ORR), progression free survival (PFS) along with overall survival (OS) in advanced melanoma, the outcome in patient with melanoma CNS metastases remains poor, especially when symptomatic. We aimed to investigate the intra-CNS clinical and/or morphological response rates of patients with stage IV BRAF-mutated melanoma to a combined anti-PD1/dual targeted anti-BRAF/anti-MEK therapy implemented after CNS disease progression despite prior anti-BRAF/anti-MEK therapy.Methods: a monocenter retrospective analysis was conducted from January 2017 to January 2022. The response was defined by a steady of improved statue. Clinical evaluation was monthly performed and morphological evaluation resulted of imaging comparison every 3 months, at minimum.Results: after a mean follow-up of 2.59 (±2.43) months under tritherapy, 1/17 patients had intra-CNS clinical and morphological response. No statistically significant difference, whether or not an additional local therapy was applied, was observed. 1/17 had to stop immunotherapy du to a grade 4 toxicity. Means PFS and OS were estimated at 2.59 and 4.12 months respectively.Conclusion: despite our low effective good, we can conclude that real life tritherapy is not effective on BRAF mutated melanoma CNS metastases.

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