Article ; Online: Efficiency and tolerance of second-line triple BRAF inhibitor/MEK inhibitor/anti-PD1 combined therapy in BRAF mutated melanoma patients with central nervous system metastases occurring during first-line combined targeted therapy: a real-life survey.
2024 Volume 34, Issue 3, Page(s) 241–247
Abstract: Although current systemic therapies significantly improved the outcome of advanced melanoma, the prognosis of patient with central nervous system (CNS) metastases remains poor especially when clinically symptomatic. We aimed to investigate the efficiency ...
| Abstract | Although current systemic therapies significantly improved the outcome of advanced melanoma, the prognosis of patient with central nervous system (CNS) metastases remains poor especially when clinically symptomatic. We aimed to investigate the efficiency of CNS targets and tolerance of second-line combined anti-PD1/dual-targeted anti-BRAF/anti-MEK therapy implemented in patients with CNS progression after initially efficient first-line combined targeted therapy in patients with BRAF-mutated melanoma in a real-life setting. A monocentric retrospective analysis including all such patients treated from January 2017 to January 2022 was conducted in our tertiary referral center. The response of CNS lesions to second-line triple therapy was assessed through monthly clinical and at least quarterly morphological (according to RECIST criteria) evaluation. Tolerance data were also collected. Seventeen patients were included with a mean follow-up of 2.59 (±2.43) months. Only 1 patient displayed a significant clinical and morphological response. No statistically significant difference was observed between patients receiving or not additional local therapy (mainly radiotherapy) as to response achievement. Immunotherapy was permanently discontinued in 1 patient owing to grade 4 toxicity. Mean PFS and OS after CNS progression were 2.59 and 4.12 months, respectively. In this real-life survey, the subsequent addition of anti-PD1 to combined targeted therapy in melanoma patients with upfront CNS metastases did not result in significant response of CNS targets in most BRAF mutated melanoma patients with secondary CNS progression after initially successful first-line combined targeted therapy. |
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| MeSH term(s) | Humans ; Melanoma/drug therapy ; Melanoma/genetics ; Melanoma/pathology ; Female ; Male ; Proto-Oncogene Proteins B-raf/genetics ; Middle Aged ; Aged ; Retrospective Studies ; Central Nervous System Neoplasms/secondary ; Central Nervous System Neoplasms/drug therapy ; Adult ; Skin Neoplasms/drug therapy ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Immune Checkpoint Inhibitors/therapeutic use ; Immune Checkpoint Inhibitors/pharmacology ; Mutation ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Aged, 80 and over |
| Chemical Substances | Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; BRAF protein, human (EC 2.7.11.1) ; Protein Kinase Inhibitors ; Immune Checkpoint Inhibitors ; Programmed Cell Death 1 Receptor |
| Language | English |
| Publishing date | 2024-03-28 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 1095779-0 |
| ISSN | 1473-5636 ; 0960-8931 |
| ISSN (online) | 1473-5636 |
| ISSN | 0960-8931 |
| DOI | 10.1097/CMR.0000000000000963 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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