Biomarker-driven therapies for metastatic uveal melanoma: A prospective precision oncology feasibility study

Leyvraz, Serge; Konietschke, Frank; Peuker, Caroline; Schuette, Moritz; Kessler, Thomas; Ochsenreither, Sebastian; Ditzhaus, Marc; Spruenken, Erin D.; Doerpholz, Gina; Lamping, Mario; Rieke, Damian T.; Klinghammer, Konrad; Burock, Susen; Ulrich, Claas; Poch, Gabriela; Schaefer, Reinhold; Klauschen, Frederick; Joussen, Antonia; Yaspo, Marie-Laure und Keilholz, Ulrich (2022): Biomarker-driven therapies for metastatic uveal melanoma: A prospective precision oncology feasibility study. In: European Journal of Cancer, Bd. 169: S. 146-155

Abstract

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 (wholegenome, 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. (C) 2022 Elsevier Ltd. All rights reserved.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0959-8049
• Sprache: Englisch