Tumor Genomic Testing for >4000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib).

Successful implementation of genomic testing in clinical practice is critical for identification of men with metastatic castration-resistant prostate cancer (mCRPC) eligible for olaparib and future molecularly targeted therapies.

An investigational clinical trial assay, based on the FoundationOne®CDx tissue test, was used to prospectively identify patients with qualifying homologous recombination repair (HRR) gene alterations in the phase III PROfound study. Evaluation of next-generation sequencing (NGS) tissue test outcome against pre-analytical parameters was performed to identify key factors influencing NGS result generation.

4858 tissue samples from 4047 patients were tested and reported centrally. NGS results were obtained in 58% (2792/4858) of samples, equating to 69% of patients. Of samples submitted, 83% were primary tumor samples (96% were archival and 4% newly obtained). Almost 17% were metastatic tumor samples (60% were archival and 33% newly obtained). NGS results were generated more frequently from newly obtained compared with archival samples (63.9% v. 56.9%), and metastatic compared with primary samples (63.9% v. 56.2%). Although generation of an NGS result declined with increasing sample age, approximately 50% of samples aged >10 years generated results. While higher tumor content and DNA yield resulted in greater success in obtaining NGS results, other factors, including selection and preservation of samples, may also have had an impact.

The PROfound study demonstrates that tissue testing to identify HRR alterations is feasible and that high-quality tumor tissue samples are key to obtaining NGS results and identifying patients with mCRPC who may benefit from olaparib treatment.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 Jan 28 [Epub ahead of print]

Maha Hussain, Claire Corcoran, Caroline Sibilla, Karim Fizazi, Fred Saad, Neal Shore, Shahneen Sandhu, Joaquin Mateo, David Olmos, Niven Mehra, Michael P Kolinsky, Guilhem Roubaud, Mustafa Ӧzgüroǧlu, Nobuaki Matsubara, Craig Gedye, Young Deuk Choi, Charles Padua, Alexander Kohlmann, Robert Huisden, Julia A Elvin, Jinyu Kang, Carrie A Adelman, Allison Allen, Christian Poehlein, Johann de Bono

Hematology/Oncology, Northwestern University ., Precision Medicine & Biosamples, R&D Oncology, AstraZeneca (Australia)., AstraZeneca (United Kingdom)., Department of Medical Oncology, Institut Gustave Roussy, University of Paris Sud., Department of Surgery, Centre Hospitalier de l'Université de Montréal, Université de Montréal., Atlantic Urology Clinics., Division of Cancer Medicine, Peter MacCallum Cancer Centre and the University of Melbourne., Prostate Cancer Translational Research, Vall d'Hebron Institute of Oncology and Vall d'Hebron University Hospital., Clinical Research programme, Spanish National Cancer Research Centre., Medical Oncology, Radboud University Nijmegen Medical Centre., Cross Cancer Institute and University of Alberta., Institut Bergonie., Medical Oncology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty., Breast and Medical Oncology, National Cancer Center Hospital East., School of Biomedical Sciences and Pharmacy, University of Newcastle., Department of Urology, Yonsei University College of Medicine., Centro de Pesquisa, Cetus Medicina Oncologica., Precision Medicine, R&D Oncology, AstraZeneca (United Kingdom)., Pathology and Diagnostic Medicine, Foundation Medicine Inc., AstraZeneca (United States)., Global Medical Affairs, AstraZeneca (United Kingdom)., Merck & Co, Inc., Clinical Studies, Institute of Cancer Research.

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