TY - JOUR
T1 - Genomic Testing in Patients with Metastatic Castration-resistant Prostate Cancer
T2 - A Pragmatic Guide for Clinicians
AU - Merseburger, Axel S
AU - Waldron, Nick
AU - Ribal, Maria J
AU - Heidenreich, Axel
AU - Perner, Sven
AU - Fizazi, Karim
AU - Sternberg, Cora N
AU - Mateo, Joaquin
AU - Wirth, Manfred P
AU - Castro, Elena
AU - Olmos, David
AU - Petrylak, Daniel P
AU - Chowdhury, Simon
N1 - Funding Information:
Financial disclosures: Axel S. Merseburger certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Axel S. Merseburger has served as principal investigator or subinvestigator for clinical studies by Clovis Oncology, Astellas, Bayer, GlaxoSmithKline, Ipsen, Janssen, Novartis, Pfizer, Teva, and Wyeth; has served as a speaker for Astellas, Bayer, GlaxoSmithKline, Hexal, Ipsen, Janssen, Novartis, Sanofi Aventis, and Teva; has served on advisory boards for Clovis Oncology, Astellas, Bayer, Ipsen, Janssen, Novartis, Pfizer, and Teva; and has received research grants from Wyeth. Axel Heidenreich has served as a consultant for Astellas, Bayer, Ipsen, and Sanofi; has served on advisory boards for Amgen, Astellas, Bayer, Ipsen, Jansen, and Sanofi; has received honoraria from Amgen, Astellas, Bayer, Ferring, Ipsen, Jansen, Pfizer, Sanofi, and Takeda; and has received research grants from Amgen, Astellas, and Sanofi. Sven Perner has served as a speaker for Astellas, AstraZeneca, Bristol-Myers Squibb, Novartis, MetaSystems, Merck/Merck Sharp & Dohme, Roche, and Ventana; has served on advisory boards for Astellas, AstraZeneca, Bristol-Myers Squibb, CeGaT, MetaSystems, Merck/Merck Sharp & Dohme, Novartis, Roche, and Ventana; and has received research grants from Bristol-Myers Squibb and Ventana. Karim Fizazi has received personal fees from Amgen, Astellas, AstraZeneca, Bayer, Clovis, CureVac, ESSA, Janssen, Orion Pharma, Roche/Genentech, and Sanofi. Cora N. Sternberg has received consultancy fees or honoraria from Astellas, AstraZeneca, Bayer, Janssen, Novartis, Sanofi, Clovis, Janssen, Pfizer, and Roche/Genentech. Joaquin Mateo has participated on advisory boards for Amgen, AstraZeneca, Clovis Oncology, Janssen, MSD, and Roche; and has received research funding from AstraZeneca and Pfizer Oncology. Elena Castro has participated in advisory boards for AstraZeneca, Astellas, Bayer, Janssen-Cilag, MSD, and Pfizer; has received speaker fees from Astellas, AstraZeneca, Bayer, Clovis, Janssen-Cilag, Pfizer, and Roche; and has received institutional research funding from AstraZeneca, Bayer, and Janssen-Cilag. David Olmos reports advisory roles for Clovis Oncology, AstraZeneca, Bayer, and Janssen; travel from Bayer, Ipsen, and Janssen; honoraria from Bayer, Janssen, and Sanofi; and research funding from Astellas/Medivation, AstraZeneca, Bayer, Genentech/Roche, Janssen, Pfizer, and Tokai Pharmaceuticals. Daniel P. Petrylak reports having stock or other ownership interests in Bellicum Pharmaceuticals and TYME; has served in a consulting or advisory role for Clovis Oncology, Ada Cap, Amgen, Astellas Pharma, AstraZeneca, Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb, Exelixis, Eli Lilly, Incyte, Janssen Pharmaceuticals, Pfizer, Pharmacyclics, Roche, Seattle Genetics, and UroGen Pharma; has given expert testimony for Celgene and Sanofi; and has received institutional research funding from Clovis Oncology, Ada Cap, Astellas Pharma, AstraZeneca, Bayer AG, Bristol-Myers Squibb, Eli Lilly, Endocyte, Genentech, Innocrin Pharma, MedImmune, Medivation, Merck, Novartis, Pfizer, Progenics, Roche, Sanofi, and Seattle Genetics. Simon Chowdhury reports advisory roles for Clovis Oncology, Astellas Pharma, Bayer, Janssen-Cilag, and Pfizer; stock in Curve Life; speaker bureau participation for Pfizer; honoraria from Clovis Oncology and Novartis; and research funding from Clovis Oncology and Sanofi Aventis. The remaining authors have nothing to disclose.
Funding Information:
Funding/Support and role of the sponsor: Writing and editorial assistance funded by Clovis Oncology .
Publisher Copyright:
© 2021 European Association of Urology
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - CONTEXT: Genomic testing is becoming increasingly important in patients with advanced prostate cancer (PC) and is being incorporated in clinical practice to guide treatment.OBJECTIVE: To review the current understanding of genomic alterations and the status of genomic testing in patients with metastatic castration-resistant PC (mCRPC), and the potential use of genomic tests in clinical practice.EVIDENCE ACQUISITION: We reviewed recent publications (past 15 yr) from PubMed, proceedings of scientific conferences, and published guidelines. Reports on mCRPC in the following areas were selected: development, testing, and validation of techniques for identifying genomic alterations; molecular characterization; and trials of genetically targeted therapies.EVIDENCE SYNTHESIS: mCRPC tumors harbor molecular alterations that are possible targets for treatment, and a number of therapies are in development to exploit these alterations (eg, PD-1 inhibitors, PARP inhibitors, tyrosine kinase inhibitors). Next-generation sequencing of DNA from tumor tissue can identify somatic alterations that would not be identified by germline testing. Work is ongoing to evaluate the use of less invasive somatic testing methods (eg, sequencing of cell-free circulating tumor DNA). Current international guidelines recommend germline and/or somatic testing for men with advanced and/or high-risk PC regardless of family history to identify those with homologous recombination repair gene mutations or mismatch repair defects/microsatellite instability who may be eligible for treatment with a PARP inhibitor or pembrolizumab, respectively.CONCLUSIONS: Genomic testing for mCRPC may provide information on prognostic, predictive, and resistance biomarkers. Although the incorporation of testing into clinical practice remains challenging, routine genomic testing of men with advanced PC is recommended to guide management and treatment decisions.PATIENT SUMMARY: Similar to many cancers, prostate cancer is caused by defects in the cancer's DNA, which are called genetic or genomic defects. New treatments targeting these defects are approved for metastatic castration-resistant prostate cancer. Specific new tests are under development to detect these potentially treatable genetic defects.
AB - CONTEXT: Genomic testing is becoming increasingly important in patients with advanced prostate cancer (PC) and is being incorporated in clinical practice to guide treatment.OBJECTIVE: To review the current understanding of genomic alterations and the status of genomic testing in patients with metastatic castration-resistant PC (mCRPC), and the potential use of genomic tests in clinical practice.EVIDENCE ACQUISITION: We reviewed recent publications (past 15 yr) from PubMed, proceedings of scientific conferences, and published guidelines. Reports on mCRPC in the following areas were selected: development, testing, and validation of techniques for identifying genomic alterations; molecular characterization; and trials of genetically targeted therapies.EVIDENCE SYNTHESIS: mCRPC tumors harbor molecular alterations that are possible targets for treatment, and a number of therapies are in development to exploit these alterations (eg, PD-1 inhibitors, PARP inhibitors, tyrosine kinase inhibitors). Next-generation sequencing of DNA from tumor tissue can identify somatic alterations that would not be identified by germline testing. Work is ongoing to evaluate the use of less invasive somatic testing methods (eg, sequencing of cell-free circulating tumor DNA). Current international guidelines recommend germline and/or somatic testing for men with advanced and/or high-risk PC regardless of family history to identify those with homologous recombination repair gene mutations or mismatch repair defects/microsatellite instability who may be eligible for treatment with a PARP inhibitor or pembrolizumab, respectively.CONCLUSIONS: Genomic testing for mCRPC may provide information on prognostic, predictive, and resistance biomarkers. Although the incorporation of testing into clinical practice remains challenging, routine genomic testing of men with advanced PC is recommended to guide management and treatment decisions.PATIENT SUMMARY: Similar to many cancers, prostate cancer is caused by defects in the cancer's DNA, which are called genetic or genomic defects. New treatments targeting these defects are approved for metastatic castration-resistant prostate cancer. Specific new tests are under development to detect these potentially treatable genetic defects.
UR - http://www.scopus.com/inward/record.url?scp=85099799468&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/8102884f-1e71-34bd-98e0-adcd30f37443/
U2 - 10.1016/j.eururo.2020.12.039
DO - 10.1016/j.eururo.2020.12.039
M3 - Scientific review articles
C2 - 33494937
AN - SCOPUS:85099799468
SN - 0302-2838
VL - 79
SP - 519
EP - 529
JO - European Urology
JF - European Urology
IS - 4
ER -
