Molecularly Matched Targeted Therapy: a Promising Approach for Refractory Metastatic Melanoma

Overview

Journal Oncologist

Publisher Oxford University Press

Specialty Oncology

Date 2024 May 18

PMID 38761384

Authors

Emily Connell

Emilie Gerard

Benedicte Oules

Florence Brunet-Possenti

Anouck Lamoureux

Hugo Bonnefille

Sorilla Mary-Prey

Ana Carrasquilla

Stephane Mouret

Nora Kramkimel

Candice Lesage

Pierre-Emmanuel Stoebner

Axel Bartoli

Sandrine Monestier

Florian Correard

Audrey Gros

Arnaud Jeanson

LHoucine Ouafik

Caroline Gaudy-Marqueste

Pascale Tomasini

Julie Charles

Mona Amini-Adle

Nausicaa Malissen

Affiliations

Soon will be listed here.

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.

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