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Biomarker-driven therapies for metastatic uveal melanoma: A prospective precision oncology feasibility study
Serge Leyvraz1, Frank Konietschke2, Caroline Peuker3
1Charité Comprehensive Cancer Center, Charité Universitätsmedizin, Berlin, Germany.
Background:
Targeted therapies for metastatic uveal melanoma have shown limited benefit in biomarker-unselected populations. The Treat20 Plus study prospectively evaluated the feasibility of a precision oncology strategy in routine clinical practice.
Patients And Methods:
Fresh biopsies were analyzed by high-throughput genomics (whole-genome, whole-exome, and RNA sequencing). A multidisciplinary molecular and immunologic tumor board (MiTB) made individualized treatment recommendations based on identified molecular aberrations, patient situation, drug, and clinical trial availability. Therapy selection was at the discretion of the treating physician. The primary endpoint was the feasibility of the precision oncology clinical program.
Results:
Molecular analyses were available for 39/45 patients (87%). The MiTB provided treatment recommendations for 40/45 patients (89%), of whom 27/45 (60%) received ≥1 matched therapy. First-line matched therapies included MEK inhibitors (n = 15), MET inhibitors (n = 10), sorafenib (n = 1), and nivolumab (n = 1). The best response to first-line matched therapy was partial response in one patient (nivolumab based on tumor mutational burden), mixed response in two patients, and stable disease in 12 patients for a clinical benefit of 56%. The matched therapy population had a median progression-free survival and overall survival of 3.3 and 13.9 months, respectively. The growth modulation index with matched therapy was >1.33 in 6/17 patients (35%) with prior systemic therapy, suggesting clinical benefit.
Conclusions:
A precision oncology approach was feasible for patients with metastatic uveal melanoma, with 60% receiving a therapy matched to identify molecular aberrations. The clinical benefit after checkpoint inhibitors highlights the value of tumor mutational burden testing.
Insights
Precision oncology is feasible for metastatic uveal melanoma, with 60% of patients receiving matched therapies. Tumor mutational burden testing is valuable, especially for checkpoint inhibitor efficacy.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Metastatic uveal melanoma (MUM) targeted therapies show limited success in unselected groups.
- A precision oncology strategy was evaluated in routine clinical practice for MUM.
Purpose of the Study:
- To assess the feasibility of a precision oncology strategy for metastatic uveal melanoma.
- To evaluate individualized treatment recommendations based on molecular aberrations.
Main Methods:
- High-throughput genomics (whole-genome, whole-exome, RNA sequencing) on fresh biopsies.
- Multidisciplinary molecular and immunologic tumor board (MiTB) for treatment recommendations.
- Physician discretion in therapy selection based on MiTB guidance.
Main Results:
- Molecular analyses were feasible in 87% of patients.
- MiTB provided recommendations for 89%, with 60% receiving matched therapy.
- Clinical benefit observed in 56% of patients receiving first-line matched therapy, including MEK and MET inhibitors.
Conclusions:
- Precision oncology is a feasible approach for metastatic uveal melanoma.
- 60% of patients received therapies matched to molecular aberrations.
- Tumor mutational burden testing is valuable, particularly for checkpoint inhibitor response.
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