Published November 2022
| Version v1
Journal article
Non-V600E/K BRAF Mutations in Metastatic Melanoma: Molecular Description, Frequency, and Effectiveness of Targeted Therapy in a Large National Cohort
Creators
- Girod, Manon
- Dalle, Stéphane
- Mortier, Laurent
- Dalac, Sophie
- Leccia, Marie-Thèrèse
- Dutriaux, Caroline
- Montaudié, Henri
- de Quatrebarbes, Julie
- Lesimple, Thierry
- Brunet-Possenti, Florence
- Saiag, Philippe
- Maubec, Eve
- Legoupil, Delphine
- Stoebner, Pierre-Emmanuel
- Arnault, Jean Philippe
- Lefevre, Wendy
- Lebbe, Celeste
- Dereure, Olivier
Contributors
Others:
- Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
- Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL) ; Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Hôpital Claude Huriez [Lille] ; CHU Lille
- Hôpital du Bocage ; Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
- Hôpital la Tronche
- Service de dermatologie [Bordeaux] ; Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux] ; CHU Bordeaux [Bordeaux]
- Service de Dermatologie [Nice] ; Hôpital Archet 2 [Nice] (CHU)
- Centre méditerranéen de médecine moléculaire (C3M) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)
- Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
- CRLCC Eugène Marquis (CRLCC)
- AP-HP - Hôpital Bichat - Claude Bernard [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Hôpital Ambroise Paré [AP-HP]
- Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
- Hôpital Avicenne [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)
- Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes) ; Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)
- CHU Amiens-Picardie
- Service de Dermatologie [AP-HP Hôpital Saint-Louis] ; Hopital Saint-Louis [AP-HP] (AP-HP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Pathogenesis and Control of Chronic and Emerging Infections (PCCEI) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM)
Description
Purpose: Mitogen-activating protein kinase inhibitors (MAPKis) are largely used in V600E/K BRAF–mutated metastatic melanomas, but data regarding effectiveness of targeted therapy in patients with rare BRAF mutations and molecular description of these infrequent mutations are scarce. Patients and methods: A multicenter study was conducted on patients with metastatic melanoma harboring a well-identified mutation of BRAF and enrolled from March 2013 to June 2021 in the French nationwide prospective cohort MelBase. The molecular BRAF mutation pattern, response to MAPKis when applicable, and survival data were analyzed. Results: Of 856 selected patients, 51 (6%) harbored a non-V600E/K BRAF mutation involving codons V600 (24 of 51, 47%; V600G 27.4%, V600R 15.6%), K601 (6 of 51, 11.7%), and L597 (4 of 51, 7.8%). An objective response to MAPKis either BRAF inhibitor (BRAFi) alone or combined with MEK inhibitor was achieved in 56% (353 of 631) of V600E/K, 58% (11 of 19) of non-E/K V600, and 22% (2 of 9) of non-V600 BRAF-mutated patients, with a median progression-free survival of 7.7, 7.8, and 2.8 months, respectively. Overall, objective response rate was higher with BRAFi + MEK inhibitor combination than with BRAFi in monotherapy for each subset. Conclusion: Rare BRAF mutations are not anecdotal in the metastatic melanoma population. Although data interpretation must remain careful owing to the limited size of some subsets of patients, non-E/K V600 BRAF mutations seem to confer a high sensitivity to targeted therapy, whereas MAPKis seem less effective in patients with non-V600 BRAF mutations. However, this strategy may be used as an alternative option in the case of immunotherapy failure in the latter population.
Abstract
International audienceAdditional details
Identifiers
- URL
- https://hal.science/hal-04049589
- URN
- urn:oai:HAL:hal-04049589v1
Origin repository
- Origin repository
- UNICA