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Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib).

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ICR Author
De Bono, Johann
Author
Hussain, M
Corcoran, C
Sibilla, C
Fizazi, K
Saad, F
Shore, N
Sandhu, S
Mateo, J
Olmos, D
Mehra, N
Kolinsky, MP
Roubaud, G
Özgüroǧlu, M
Matsubara, N
Gedye, C
Choi, YD
Padua, C
Kohlmann, A
Huisden, R
Elvin, JA
Kang, J
Adelman, CA
Allen, A
Poehlein, C
de Bono, J
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Type
Journal Article
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Abstract
<h4>Purpose</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
URI
https://repository.icr.ac.uk/handle/internal/5096
DOI
https://doi.org/10.1158/1078-0432.ccr-21-3940
https://doi.org/10.1158/1078-0432.ccr-21-3940
 
Collections
  • Clinical Studies
Research team
Prostate Cancer Targeted Therapy Group
Language
eng
Date accepted
2022-01-26
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2022, 28 (8), pp. 1518 - 1530

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