Katrin Schaper-Gerhardt1, Steven Okoye2, Rudolf Herbst3, Jens Ulrich4, Patrick Terheyden5, Claudia Pföhler6, Jochen S Utikal7, Alexander Kreuter8, Peter Mohr9, Edgar Dippel10, Imke Satzger11, Antje Sucker12, Dirk Schadendorf13, Selma Ugurel14, Ralf Gutzmer15. 1. Skin Cancer Center Hannover, Dept. of Dermatology and Allergy, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: schaper-gerhardt.katrin@mh-hannover.de. 2. Skin Cancer Center Hannover, Dept. of Dermatology and Allergy, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: okoye.steven@mh-hannover.de. 3. Department of Dermatology, Helios Clinic, Erfurt, Germany. Electronic address: rudolf.herbst@helios-kliniken.de. 4. Department of Dermatology, Quedlinburg, Germany. Electronic address: jens.ulrich@harzklinikum.com. 5. Department of Dermatology, University of Lübeck, Lübeck, Germany. Electronic address: Patrick.terheyden@uksh.de. 6. Department of Dermatology, Saarland University Medical School, Homburg, Germany. Electronic address: Claudia.pfoehler@uks.eu. 7. Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany. Electronic address: j.utikal@dkfz-heidelberg.de. 8. Department of Dermatology, Venereology, and Allergology, HELIOS St. Elisabeth Hospital Oberhausen, University Witten-Herdecke, Germany. Electronic address: alexander.kreuter@helios-kliniken.de. 9. Department of Dermatology, Elbe Clinic, Buxtehude, Germany. Electronic address: Peter.Mohr@elbekliniken.de. 10. Department of Dermatology, Ludwigshafen Hospital, Ludwigshafen, Germany. Electronic address: Dippele@klilu.de. 11. Skin Cancer Center Hannover, Dept. of Dermatology and Allergy, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: Satzger.imke@mh-hannover.de. 12. Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: antje.sucker@uk-essen.de. 13. Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: dirk.schadendorf@uk-essen.de. 14. Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: selma.ugurel@uk-essen.de. 15. Skin Cancer Center Hannover, Dept. of Dermatology and Allergy, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: Gutzmer.ralf@mh-hannover.de.
Abstract
BACKGROUND: Targeted therapies with BRAF plus MEK inhibitors (BRAFi; MEKi) represent the major treatment strategy for patients with BRAF-mutated metastatic melanoma (MM). Previous analyses suggested a correlation between programmed death-ligand 1 (PD-L1) expression in tumour tissues and the outcome of targeted therapies. This study investigated PD-L1 as a potential predictive biomarker of BRAFi-based targeted therapies in MM patients. PATIENTS AND METHODS: We analysed two independent cohorts of BRAF V600-mutated MM patients undergoing BRAFi-based therapies for PD-L1 expression in pre-treatment tumour tissues. The oligocentre cohort 1 included 83 patients whose tumour tissues were analysed retrospectively with the anti-PD-L1 antibody clone E1L3N. The multicentre cohort 2 included 58 patients whose tumour tissues were analysed prospectively within the framework of the "Registry of the Arbeitsgemeinschaft Dermatologische Onkologie" (ADOREG) and "Tissue Registry in Melanoma" (TRIM) project using the anti-PD-L1 antibody clone 28-8. RESULTS: PD-L1 expression in pre-treatment tumour tissue did not correlate with response or survival to BRAFi-based therapies in both MM patient cohorts. This finding was not influenced by retrospective versus prospective immunohistochemistry analyses, oligocentre versus multicentre cohorts or the different anti-PD-L1 antibody clones used. In cohort 1, PD-L1 positivity was detected in tumour tissue of 41.0% and 18.1% of patients (cut-off 1% and 5%, respectively). In cohort 2, 58.6% and 39.7% of patients showed PD-L1 positivity (cut-off 1% and 5%, respectively). CONCLUSION: In two independent cohorts including a total of 141 MM patients, PD-L1 expression in tumour tissue did not correlate with the outcome of BRAFi-based treatment. Therefore, PD-L1 cannot be recommended for the use as a predictive biomarker of BRAFi-based therapy in BRAF V600-mutated MM.
BACKGROUND: Targeted therapies with BRAF plus MEK inhibitors (BRAFi; MEKi) represent the major treatment strategy for patients with BRAF-mutated metastatic melanoma (MM). Previous analyses suggested a correlation between programmed death-ligand 1 (PD-L1) expression in tumour tissues and the outcome of targeted therapies. This study investigated PD-L1 as a potential predictive biomarker of BRAFi-based targeted therapies in MMpatients. PATIENTS AND METHODS: We analysed two independent cohorts of BRAF V600-mutated MMpatients undergoing BRAFi-based therapies for PD-L1 expression in pre-treatment tumour tissues. The oligocentre cohort 1 included 83 patients whose tumour tissues were analysed retrospectively with the anti-PD-L1 antibody clone E1L3N. The multicentre cohort 2 included 58 patients whose tumour tissues were analysed prospectively within the framework of the "Registry of the Arbeitsgemeinschaft Dermatologische Onkologie" (ADOREG) and "Tissue Registry in Melanoma" (TRIM) project using the anti-PD-L1 antibody clone 28-8. RESULTS:PD-L1 expression in pre-treatment tumour tissue did not correlate with response or survival to BRAFi-based therapies in both MMpatient cohorts. This finding was not influenced by retrospective versus prospective immunohistochemistry analyses, oligocentre versus multicentre cohorts or the different anti-PD-L1 antibody clones used. In cohort 1, PD-L1 positivity was detected in tumour tissue of 41.0% and 18.1% of patients (cut-off 1% and 5%, respectively). In cohort 2, 58.6% and 39.7% of patients showed PD-L1 positivity (cut-off 1% and 5%, respectively). CONCLUSION: In two independent cohorts including a total of 141 MMpatients, PD-L1 expression in tumour tissue did not correlate with the outcome of BRAFi-based treatment. Therefore, PD-L1 cannot be recommended for the use as a predictive biomarker of BRAFi-based therapy in BRAF V600-mutated MM.
Authors: Ramy R Saleh; Jordan L Scott; Nicholas Meti; Danielle Perlon; Rouhi Fazelzad; Alberto Ocana; Eitan Amir Journal: Mol Diagn Ther Date: 2022-02-01 Impact factor: 4.074
Authors: Allison M Martin; W Robert Bell; Ming Yuan; Lauren Harris; Bradley Poore; Antje Arnold; Elizabeth L Engle; Laura Asnaghi; Michael Lim; Eric H Raabe; Charles G Eberhart Journal: J Neuropathol Exp Neurol Date: 2020-01-01 Impact factor: 3.148
Authors: Miguel-Angel Berciano-Guerrero; Rocío Lavado-Valenzuela; Aurelio Moya; Luis delaCruz-Merino; Fátima Toscano; Javier Valdivia; Victoria Castellón; Fernando Henao-Carrasco; Pilar Sancho; Juan-Luis Onieva-Zafra; Ismael Navas-Delgado; Antonio Rueda-Dominguez; Elisabeth Perez-Ruiz; Emilio Alba Journal: Biomedicines Date: 2022-01-26