학술논문
Molecularly matched targeted therapy: a promising approach for refractory metastatic melanoma.
Document Type
Academic Journal
Author
Connell E; Dermatology and Skin Cancer Department, Aix Marseille University, APHM, CRCM Inserm U1068, CNRS U7258, Marseille, France.; Department of Early Phase Cancer Trial Center (CEPCM) 'CLIP2,' Aix Marseille University, APHM, Marseille, France.; Gerard É; Dermatology Department, CHU de Bordeaux, Bordeaux, France.; Oules B; Dermatology Department, Cochin Hospital, Paris, France.; Brunet-Possenti F; Dermatology Department, Bichat Claude-Bernard Hospital, Paris, France.; Lamoureux A; Dermatology Department, Montpellier Cancer Institute, Montpellier, France.; Bonnefille H; Dermatology Department, CHU de Nîmes, Nîmes, France.; Mary-Prey S; Dermatology Department, CHU de Bordeaux, Bordeaux, France.; Carrasquilla A; Dermatology Department, Leon Bérard Cancer Center, Lyon, France.; Mouret S; Dermatology Department, CHU Grenoble Alpes, University Grenoble Alpes, INSERM U 1209, CNRS UMR 5309, Institut for Advanced Biosciences, Grenoble, France.; Kramkimel N; Dermatology Department, Cochin Hospital, Paris, France.; Lesage C; Dermatology Department, CHU de Montpellier, Montpellier, France.; Stoebner PE; Dermatology Department, CHU de Nîmes, Nîmes, France.; Bartoli A; Radiology Department, Aix Marseille University, APHM, CERIMED, Marseille, France.; Monestier S; Dermatology and Skin Cancer Department, Aix Marseille University, APHM, CRCM Inserm U1068, CNRS U7258, Marseille, France.; Department of Early Phase Cancer Trial Center (CEPCM) 'CLIP2,' Aix Marseille University, APHM, Marseille, France.; Correard F; Pharmacy Department, Aix Marseille University, APHM, Marseille, France.; Gros A; Tumor Biology and Tumor Bank Department, University Hospital of Bordeaux, Bordeaux, France.; Jeanson A; Department of Early Phase Cancer Trial Center (CEPCM) 'CLIP2,' Aix Marseille University, APHM, Marseille, France.; Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, CNRS, INSERM, CRCM, APHM, Marseille, France.; Ouafik L; Oncobiology Department, Aix Marseille University, APHM, CNRS, INP, Inst Neurophysiopathol, Marseille, France.; Gaudy-Marqueste C; Dermatology and Skin Cancer Department, Aix Marseille University, APHM, CRCM Inserm U1068, CNRS U7258, Marseille, France.; Department of Early Phase Cancer Trial Center (CEPCM) 'CLIP2,' Aix Marseille University, APHM, Marseille, France.; Tomasini P; Department of Early Phase Cancer Trial Center (CEPCM) 'CLIP2,' Aix Marseille University, APHM, Marseille, France.; Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, CNRS, INSERM, CRCM, APHM, Marseille, France.; Charles J; Dermatology Department, CHU Grenoble Alpes, University Grenoble Alpes, INSERM U 1209, CNRS UMR 5309, Institut for Advanced Biosciences, Grenoble, France.; Amini-Adle M; Dermatology Department, Leon Bérard Cancer Center, Lyon, France.; Malissen N; Dermatology and Skin Cancer Department, Aix Marseille University, APHM, CRCM Inserm U1068, CNRS U7258, Marseille, France.; Department of Early Phase Cancer Trial Center (CEPCM) 'CLIP2,' Aix Marseille University, APHM, Marseille, France.
Source
Publisher: Oxford University Press Country of Publication: England NLM ID: 9607837 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-490X (Electronic) Linking ISSN: 10837159 NLM ISO Abbreviation: Oncologist Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Only a fraction of patients with metastatic melanoma derive durable benefit from approved treatments. The clinical impact of personalized medicine strategies for melanoma, apart from BRAF, NRAS, or CKIT targeting, has rarely been reported.
Materials and Methods: By means of the Group of Cutaneous Oncology of the French Society of Dermatology, we retrospectively included all patients with advanced melanoma aged 18 years and older for whom molecular testing identified one or more actionable molecular alterations and who accordingly received molecularly matched therapy. We excluded patients with only BRAF, NRAS, or CKIT alterations and patients who received molecularly matched therapy for less than 15 days.
Results: We included 26 patients with a median follow-up of 8 months (1-54), a median age of 63 years (24-89), and a sex ratio of 2.7. These patients had been heavily pretreated, and 64% had elevated LDH levels. The disease control rate was 38%, with 4 cases of partial response (overall response rate: 15%) and 6 of stable disease for at least 6 months. The median duration of treatment was 3.1 months (0.9-13.5). Among patients with disease control, the median duration of control was 6.6 months (2.6-13.5) and 3 cases were ongoing at the end of the study. Patients with controlled disease had GNA11, MAP2K1, FYCO1-RAF1, HRAS, ATM, CCND1, MDM2/CDK4, and CDKN2A/NRAS alterations.
Conclusions: High-throughput sequencing followed by matched targeted therapy is a promising approach for patients with advanced melanoma refractory to approved treatments.
(© The Author(s) 2024. Published by Oxford University Press.)
Materials and Methods: By means of the Group of Cutaneous Oncology of the French Society of Dermatology, we retrospectively included all patients with advanced melanoma aged 18 years and older for whom molecular testing identified one or more actionable molecular alterations and who accordingly received molecularly matched therapy. We excluded patients with only BRAF, NRAS, or CKIT alterations and patients who received molecularly matched therapy for less than 15 days.
Results: We included 26 patients with a median follow-up of 8 months (1-54), a median age of 63 years (24-89), and a sex ratio of 2.7. These patients had been heavily pretreated, and 64% had elevated LDH levels. The disease control rate was 38%, with 4 cases of partial response (overall response rate: 15%) and 6 of stable disease for at least 6 months. The median duration of treatment was 3.1 months (0.9-13.5). Among patients with disease control, the median duration of control was 6.6 months (2.6-13.5) and 3 cases were ongoing at the end of the study. Patients with controlled disease had GNA11, MAP2K1, FYCO1-RAF1, HRAS, ATM, CCND1, MDM2/CDK4, and CDKN2A/NRAS alterations.
Conclusions: High-throughput sequencing followed by matched targeted therapy is a promising approach for patients with advanced melanoma refractory to approved treatments.
(© The Author(s) 2024. Published by Oxford University Press.)