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Updated: Jun 26, 2025
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Molecularly matched targeted therapy: a promising approach for refractory metastatic melanoma
Emily Connell1,2, Émilie Gerard3, Bénédicte Oules4
1Dermatology and Skin Cancer Department, Aix Marseille University, APHM, CRCM Inserm U1068, CNRS U7258, Marseille, France.
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.
Insights
Targeted therapy matched to molecular alterations shows promise for advanced melanoma patients resistant to standard treatments. This approach achieved disease control in 38% of heavily pretreated individuals.
Area of Science:
- Oncology
- Genomics
- Dermatology
Background:
- Metastatic melanoma patients often show limited durable benefit from current treatments.
- The clinical utility of personalized medicine beyond BRAF, NRAS, or CKIT mutations in melanoma is underreported.
Purpose of the Study:
- To evaluate the efficacy of molecularly matched targeted therapy for advanced melanoma patients with actionable molecular alterations.
- To assess outcomes in patients refractory to standard therapies.
Main Methods:
- Retrospective analysis of advanced melanoma patients (≥18 years) receiving molecularly matched therapy.
- Exclusion of patients with only BRAF, NRAS, or CKIT alterations or therapy <15 days.
- Molecular testing identified actionable alterations guiding targeted therapy selection.
Main Results:
- 26 heavily pretreated patients included; median follow-up 8 months.
- 38% disease control rate (15% overall response rate, 6 months stable disease).
- Controlled disease associated with alterations in GNA11, MAP2K1, RAF1, HRAS, ATM, CCND1, MDM2/CDK4, CDKN2A/NRAS.
Conclusions:
- High-throughput sequencing and matched targeted therapy offer a promising strategy for advanced melanoma.
- This approach shows potential for patients with treatment-refractory disease.
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