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

Autor: Leyvraz S; Charité Comprehensive Cancer Center, Charité Universitätsmedizin, Berlin, Germany. Electronic address: serge.leyvraz@charite.de., Konietschke F; Institut für Biometrie und Klinische Epidemiologie, Berliner Institut für Gesundheitsforschung, Charité Universitätsmedizin, Berlin, Germany., Peuker C; Klinik für Hämatologie, Onkologie und Tumorimmunologie, Charité Universitätsmedizin, Berlin, Germany., Schütte M; Alacris Theranostics, Berlin, Germany., Kessler T; Alacris Theranostics, Berlin, Germany., Ochsenreither S; Klinik für Hämatologie, Onkologie und Tumorimmunologie, And Comprehensive Cancer Center, Charité Universitätsmedizin, Berlin, Germany., Ditzhaus M; Fakultät für Statistik, Technische Universität Dortmund, Dortmund, Germany., Sprünken ED; Institut für Biometrie und Klinische Epidemiologie, Berliner Institut für Gesundheitsforschung, Charité Universitätsmedizin, Berlin, Germany., Dörpholz G; Charité Comprehensive Cancer Center, Charité Universitätsmedizin, Berlin, Germany., Lamping M; Klinik für Hämatologie, Onkologie und Tumorimmunologie, Charité Universitätsmedizin, Berlin, Germany., Rieke DT; Klinik für Hämatologie, Onkologie und Tumorimmunologie, And Comprehensive Cancer Center, Charité Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany., Klinghammer K; Klinik für Hämatologie, Onkologie und Tumorimmunologie, Charité Universitätsmedizin, Berlin, Germany., Burock S; Charité Comprehensive Cancer Center, Charité Universitätsmedizin, Berlin, Germany., Ulrich C; Klinik für Dermatologie, Venerologie und Allergologie, Charité Universitätsmedizin, Berlin, Germany., Poch G; Klinik für Dermatologie, Venerologie und Allergologie, Charité Universitätsmedizin, Berlin, Germany., Schäfer R; Charité Comprehensive Cancer Center, Charité Universitätsmedizin, Berlin, Germany., Klauschen F; Institut für Pathologie, Ludwig-Maximilians-Universität München, München, Germany., Joussen A; Klinik für Augenheilkunde, Charité Universitätsmedizin, Berlin, Germany., Yaspo ML; Otto Warburg Laboratory 'Gene Regulation and Systems Biology of Cancer' Max Planck Institute of Molecular Genetics, Berlin, Germany., Keilholz U; Charité Comprehensive Cancer Center, Charité Universitätsmedizin, Berlin, Germany.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2022 Jul; Vol. 169, pp. 146-155. Date of Electronic Publication: 2022 May 12.
DOI: 10.1016/j.ejca.2022.04.004
Abstrakt: 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.
Competing Interests: Conflict of interest statement SL reports travel and advisory board support from Immunocore and Bayer. CP reports speaker honoraria from Bristol-Myers Squibb, Novartis, Daiichi-Sankyo, EUSA Pharma and Sirtex Medical and advisory honoraria from EUSA Pharma. MS is employee of Alacris Theranostics. TK is employee of Alacris Theranostics. SO reports consultancy fees from Astra Zeneca, Bristol-Myers Squibb, Janssen Biotech, Merck. DTR reports Honoraria from Lilly, Bristol-Myers Squibb and Advisory Honoraria from Bayer and Alacris Theranostics. KK reports advisory board and conference honoraria from Merck, Sanofi, Merck Sharp & Dohme, Glycotope, Roche, Novartis and Bristol-Myers Squibb. CU reports consulting fees from Sanofi, grant for educational activities form Galderma, Beiresdorf and Almirall. GP reports consulting fees and grant for educational activities from Amgen. Novartis, Sun Pharma. Bristol-Myers Squibb, Merck Sharp & Dohme. FK is co-founder of Aignostics GmbH and has received consulting support from Roche, Novartis, Bristol-Myers Squibb, Lilly, Agilent and Iomedico. AJ reports Consultant fees from Novartis, Roche, Boehringer, Allergan, Bayer. MLY is an employee and shareholder of Alacris Theranostics. UK reports consulting fees for Merck Sharp & Dohme, travel support from Merck Serono, Pfizer, grant for educational activities from Merck Serono, Bristol-Myers Squibb, Pierre-Fabre. FK, MD, ES, GD, ML, SB, RS have no conflict of interest.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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