Abstract
Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA ), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after nextgeneration androgen receptor-directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA identified by central plasma (n 34), central tissue (n 37), or local (n 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6677-6686 |
| Number of pages | 10 |
| Journal | Clinical Cancer Research |
| Volume | 27 |
| Issue number | 24 |
| DOIs | |
| State | Published - Dec 15 2021 |
ASJC Scopus subject areas
- Oncology
- Cancer Research
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Response to Rucaparib in BRCA-Mutant Metastatic Castration-Resistant Prostate Cancer Identified by Genomic Testing in the TRITON2 Study. / Loehr, Andrea; Patnaik, Akash; Campbell, David; Shapiro, Jeremy; Bryce, Alan H.; McDermott, Ray; Sautois, Brieuc; Vogelzang, Nicholas J.; Bambury, Richard M.; Voog, Eric; Zhang, Jingsong; Piulats, Josep M.; Hussain, Arif; Ryan, Charles J.; Merseburger, Axel S.; Daugaard, Gedske; Heidenreich, Axel; Fizazi, Karim; Higano, Celestia S.; Krieger, Laurence E.; Sternberg, Cora N.; Watkins, Simon P.; Despain, Darrin; Simmons, Andrew D.; Dowson, Melanie; Golsorkhi, Tony; Chowdhury, Simon; Abida, Wassim.
In: Clinical Cancer Research, Vol. 27, No. 24, 15.12.2021, p. 6677-6686.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Response to Rucaparib in BRCA-Mutant Metastatic Castration-Resistant Prostate Cancer Identified by Genomic Testing in the TRITON2 Study
AU - Loehr, Andrea
AU - Patnaik, Akash
AU - Campbell, David
AU - Shapiro, Jeremy
AU - Bryce, Alan H.
AU - McDermott, Ray
AU - Sautois, Brieuc
AU - Vogelzang, Nicholas J.
AU - Bambury, Richard M.
AU - Voog, Eric
AU - Zhang, Jingsong
AU - Piulats, Josep M.
AU - Hussain, Arif
AU - Ryan, Charles J.
AU - Merseburger, Axel S.
AU - Daugaard, Gedske
AU - Heidenreich, Axel
AU - Fizazi, Karim
AU - Higano, Celestia S.
AU - Krieger, Laurence E.
AU - Sternberg, Cora N.
AU - Watkins, Simon P.
AU - Despain, Darrin
AU - Simmons, Andrew D.
AU - Dowson, Melanie
AU - Golsorkhi, Tony
AU - Chowdhury, Simon
AU - Abida, Wassim
N1 - Funding Information: Research support for the study: This study was funded by Clovis Oncology, Inc. Funding Information: A. Loehr reports other support from Clovis Oncology, Inc., during the conduct of the study. A. Patnaik reports other support from Clovis Oncology, Inc., during the conduct of the study as well as grants from Bristol-Myers Squibb and other support from Progenics, Laekna Inc, Exelixis, Prime, Jounce Therapeutics, Janssen, and Merck outside the submitted work. J. Shapiro has served in a consulting or advisory role for Amgen, Astellas, Ipsen, Merck, and Roche and received financial support for travel from Amgen and Merck. A.H. Bryce reports personal fees from Merck, Astellas, Bayer, and Pfizer outside the submitted work. R. McDermott reports personal fees from Clovis Oncology, Inc., during the conduct of the study as well as personal fees from Bayer, MSD, Sanofi, Janssen, Astellas, BMS, Pfizer, and Novartis outside the submitted work. B. Sautois reports other support from Clovis Oncology, Inc., during the conduct of the study as well as personal fees from Janssen, Astellas, and Sanofi outside the submitted work. N.J. Vogelzang reports personal fees from Clovis Oncology, Inc., AstraZeneca, and Pfizer during the conduct of the study. R.M. Bambury reports educational grant support and honoraria from Pfizer, Roche, Janssen, Astellas, and BMS; in addition, R.M. Bambury is the co-founder of Portable Medical Technology Ltd. J. Zhang reports personal fees from Clovis Oncology, Inc., during the conduct of the study as well as grants and personal fees from Astellas, Bayer, and AstraZeneca and personal fees from Merck outside the submitted work. J.M. Piulats reports grants and personal fees from MSD, Pfizer, and Janssen; grants from BeiGene; and nonfinancial support from Clovis Oncology, Inc., during the conduct of the study as well as personal fees from Astellas, Bayer, and Roche and grants, personal fees, and nonfinancial support from BMS outside the submitted work. A. Hussain reports other support from Clovis Oncology, Inc., during the conduct of the study as well as personal fees from Bayer, Merck, and Aveo Pharmaceuticals outside the submitted work; in addition, A. Hussain serves as institutional principal investigator (PI) on several sponsored clinical trials in prostate cancer, renal cancer, and bladder cancer where the respective sponsors provide funding directly to the institution (University of Maryland Greenebaum Comprehensive Cancer Center) to help defray costs of running the clinical trials. C.J. Ryan has received research support from Clovis Oncology, Inc., and has served as a consultant for AstraZeneca and Bayer. A.S. Merseburger reports personal fees, nonfinancial support, and other support from Clovis Oncology, Inc., during the conduct of the study as well as personal fees and nonfinancial support from AstraZeneca, Astellas, Janssen, Pfizer, and Ipsen outside the submitted work. G. Daugaard has served in a consulting or advisory role for Clovis Oncology, Inc., Astellas, AstraZeneca, Janssen, Merck, and Sanofi. A. Heidenreich reports personal fees from Clovis Oncology, Inc., during the conduct of the study as well as personal fees from Astellas, Bayer, Ipsen, Janssen, Pfizer, Takeda and MSD and grants and personal fees from Amgen and BMS outside the submitted work. K. Fizazi reports personal fees from Bayer, CureVac, and Orion and nonfinancial support from Astellas, Sanofi, Janssen, AstraZeneca, Clovis Oncology, Inc., and Novartis outside the submitted work. C.S. Higano reports grants and personal fees from Clovis Oncology, Inc., during the conduct of the study as well as personal fees and other support from Advanced Accelerator Applications, Blue Earth, Janssen, and Merck; grants from Aptevo, Emergent, Hoffman-LaRoche, and Medivation; grants, personal fees, and other support from Astellas, AstraZeneca, and Ferring; grants and personal fees from Bayer, Dendreon, Genetech, and Pfizer; and other support from Exelixis outside the submitted work. L.E. Krieger reports personal fees from Clovis Pharmaceuticals outside the submitted work. C.N. Sternberg reports personal fees from Clovis Oncology, Inc., during the conduct of the study as well as personal fees from Pfizer, BMS, Sanofi-Genzyme, MSD, Merck, Roche-Genentech, Incyte, Foundation Medicine, Immunomedics, Medscape, UroToday, Janssen, CCO Clinical, and NCI outside the submitted work. S.P. Watkins reports other support from Clovis Oncology, Inc., during the conduct of the study as well as other support from Clovis Oncology, Inc., outside the submitted work. D. Despain reports other support from Clovis Oncology, Inc., outside the submitted work; in addition, D. Despain is an employee of Clovis Oncology, Inc., the sponsor of rucaparib and the TRITON2 study. A.D. Simmons reports other support from Clovis Oncology, Inc., during the conduct of the study. M. Dowson reports personal fees from Clovis Oncology, Inc., outside the submitted work. T. Golsorkhi reports other support from Clovis Oncology, Inc., during the conduct of the study. S. Chowdhury reports grants and personal fees from Clovis Oncology, Inc., and personal fees from AstraZeneca, Novartis, Janssen, Bayer, Telix, Astellas, Huma, and Remedy Bio during the conduct of the study. W. Abida reports personal fees from Clovis Oncology, Inc., Roche, Medscape, Onclive, Clinical Education Alliance, Aptitude Health, Janssen, ORIC Pharmaceuticals, and Daiichi and other support from Clovis Oncology, Inc., during the conduct of the study as well as other support from AstraZeneca, Zenith Epigenetics, ORIC Pharmaceuticals, and Epizyme outside the submitted work. No disclosures were reported by the other authors. Funding Information: This work was funded by Clovis Oncology, Inc., and supported in part by the NCI Cancer Center Support Grant No. P30-CA008748, NCI Prostate Specialized Program of Research Excellence (SPORE) Grant No. P50-CA092629-16, Department of Defense Prostate Cancer Research Program Grant No. W81XWH-17-1-0124, and a Prostate Cancer Foundation Young Investigator Award (to W. Abida), and supported in part by a Prostate Cancer Foundation Challenge Award and NCI Prostate SPORE Grant No. P50-CA180995 (to A. Patnaik). Editorial support funded by Clovis Oncology, Inc., was provided by Shelly Lim and Stephen Bublitz of Ashfield MedComms, an Ashfield Health company. Publisher Copyright: © 2021 American Association for Cancer Research.
PY - 2021/12/15
Y1 - 2021/12/15
N2 - Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA ), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after nextgeneration androgen receptor-directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA identified by central plasma (n 34), central tissue (n 37), or local (n 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.
AB - Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA ), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after nextgeneration androgen receptor-directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA identified by central plasma (n 34), central tissue (n 37), or local (n 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.
UR - http://www.scopus.com/inward/record.url?scp=85122367564&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85122367564&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-21-2199
DO - 10.1158/1078-0432.CCR-21-2199
M3 - Article
C2 - 34598946
AN - SCOPUS:85122367564
VL - 27
SP - 6677
EP - 6686
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 24
ER -