Abstract
Purpose: 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. Patients and Methods: An investigational clinical trial assay, based on the FoundationOneCDx tissue test, was used to prospectively identify patients with qualifying homologous recombination repair gene alterations in the phase III PROfound study. Evaluation of next-generation sequencing (NGS) tissue test outcome against preanalytic parameters was performed to identify key factors influencing NGS result generation. Results: A total of 4,858 tissue samples from 4,047 patients were tested and reported centrally. NGS results were obtained in 58% (2,792/4,858) of samples (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% vs. 56.9%) and metastatic compared with primary samples (63.9% vs. 56.2%). Although generation of an NGS result declined with increasing sample age, approximately 50% of samples ages >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. Conclusions: The PROfound study shows that tissue testing to identify homologous recombination repair 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1518-1530 |
| Number of pages | 13 |
| Journal | Clinical Cancer Research |
| Volume | 28 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 15 2022 |
Funding
This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ. Medical writing assistance was provided by Juliet Fawcett, PhD for Mudskipper Business Ltd., funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. M. Hussain reports grants from AstraZeneca during the conduct of the study, as well as grants from Genentech, Pfizer, Bayer, and Arvinas and personal fees from AstraZeneca, AZ/Merck, Janssen, BMS, Daiichi Sankyo, Novartis, AstraZeneca, Merck, and Astellas outside the submitted work. C. Corcoran reports other support from AstraZeneca and Mudskipper during the conduct of the study and other support from AstraZeneca outside the submitted work, and is an employee of AstraZeneca and holds shares with the company. K. Fizazi reports other support from AstraZeneca during the conduct of the study; other support from Astellas, Amgen, Bayer, Clovis, Janssen, Novartis, and Sanofi, and personal fees from Orion outside the submitted work. F. Saad reports grants, personal fees, and nonfinancial support from AstraZeneca and Merck during the conduct of the study and grants, personal fees, and nonfinancial support from Astellas, Janssen, Bayer, Novartis, and Sanofi outside the submitted work. N. Shore reports personal fees from AstraZeneca, Merck, Invitae, Clovis Oncology, Myriad, Astellas, Pfizer, Janssen, Foundation Medicine, Tempus, and Sema4 during the conduct of the study. S. Sandhu reports grants from Merck Sharp & Dohme, AstraZeneca, Amgen, Novartis, Genentech, and Pfizer and personal fees from Merck Sharp & Dohme and AstraZeneca outside the submitted work. J. Mateo reports nonfinancial support and other support from AstraZeneca during the conduct of the study; grants and personal fees from AstraZeneca and Pfizer Oncology; and personal fees from Roche, Guardant Health, and Merck Sharp & Dohme outside the submitted work. D. Olmos reports grants, personal fees, and other support from AstraZeneca, Bayer, and Janssen; other support from F. Hoffman La-Roche/Genen-tech; and personal fees from Merck Sharp & Dohme and Clovis outside the submitted work. N. Mehra reports grants and personal fees from AstraZeneca and Merck Sharp & Dohme during the conduct of the study; personal fees from Janssen and Bayer; grants from Astellas and Bristol Myers Squibb; and grants and personal fees from Pfizer outside the submitted work. M.P. Kolinsky reports other support from AstraZeneca during the conduct of the study and personal fees from AstraZeneca, Merck, Astellas, Bayer, Bristol Myers Squibb, Eisai, Ipsen, and Janssen outside the submitted work. G. Roubaud reports grants from Bayer; personal fees from Astellas, Sanofi, and AstraZeneca; and personal fees and nonfinancial support from Janssen outside the submitted work. N. Matsubara reports grants from AstraZeneca during the conduct of the study; grants and personal fees from Janssen and Sanofi; and grants from AstraZeneca, Bayer, Roche, Merck Sharp & Dohme, Taiho, Astellas, Amgen, Eisai, Eli Lilly, Takeda, Pfizer, and Chugai outside the submitted work. C. Gedye reports personal fees from Merck EMD Serono, Merck Sharp & Dohme, Bristol Myers Squibb, Astellas, Pfizer, and AstraZeneca outside the submitted work; and C. Gedye has participated in consulting roles and advisory boards with Merck EMD Serono, MSD, BMS, Astellas, Pfizer, AstraZeneca, and Astellas. All payments and fees from these activities are directed to a third-party not-for-profit; C. Gedye does not accept any payments personally: the third party is ANZUP Cancer Trials Group unless otherwise stated, and donations can be made to ANZUP at https://www.anzup.org.au/ donate/donate.aspx to support their work to conduct clinical trials research to improve treatments of bladder, kidney, testicular, penile and prostate cancers. C. Gedye receives travel support (when we could travel!) from BMS, Astellas, MSD, was accepted in lieu of NSW Health employment contract allowances (pharma pays for conferences that would have been received via publicly funded TESL reimbursement). C. Gedye reports research funding direct to third-party (no salary or payments to individual) from Bristol Myers Squibb, Amgen, and Merck Sharp & Dohme; MRFF funding to COGNO/University of Sydney; consulting for Novotech-CRO PTY, to help them improve and enhance clinical trial concepts and proposals, aiming to make for more effective commercial cancer clinical trials; and scientific advisory committee membership with ANZUP Cancer Trials Group, COGNO, Mark Hughes Foundation, and International Kidney Cancer Consortium. A. Kohlmann reports other support from AstraZeneca during the conduct of the study and other support from AstraZeneca outside the submitted work. R. Huisden reports personal fees from AstraZeneca during the conduct of the study. J.A. Elvin reports other support from Foundation Medicine and F. Hoffmann La-Roche outside the submitted work. J. Kang reports personal fees from AstraZeneca outside the submitted work and is an employee of AstraZeneca and owns stocks of the company. C.A. Adelman reports employment and stock ownership with AstraZeneca. C. Poehlein reports other support from Merck & Company, outside the United States and Canada known as Merck Sharp & Dohme, outside the submitted work. J. de Bono reports grants and personal fees from AstraZeneca during the conduct of the study; grants and personal fees from Amgen, Astellas, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi, Eisai, Genentech/Roche, Genmab, GlaxoSmithKline, Harpoon, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Orion, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, and Vertex Pharmaceuticals and grants from Menarini/Silicon Biosystems outside the submitted work; in addition, J. de Bono has a patent for DNA repair defects PARP (ICR owned patent) and does not receive royalties issued and a patent for Abiraterone acetate (ICR owned patent) but does not receive any royalties issued. No disclosures were reported by the other authors.
ASJC Scopus subject areas
- General Medicine
