Response to Rucaparib in BRCA-Mutant Metastatic Castration-Resistant Prostate Cancer Identified by Genomic Testing in the TRITON2 Study

Andrea Loehr, Akash Patnaik, David Campbell, Jeremy Shapiro, Alan H. Bryce, Ray McDermott, Brieuc Sautois, Nicholas J. Vogelzang, Richard M. Bambury, Eric Voog, Jingsong Zhang, Josep M. Piulats, Arif Hussain, Charles J. Ryan, Axel S. Merseburger, Gedske Daugaard, Axel Heidenreich, Karim Fizazi, Celestia S. Higano, Laurence E. KriegerCora N. Sternberg, Simon P. Watkins, Darrin Despain, Andrew D. Simmons, Melanie Dowson, Tony Golsorkhi, Simon Chowdhury, Wassim Abida

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)6677-6686
Number of pages10
JournalClinical Cancer Research
Volume27
Issue number24
DOIs
StatePublished - Dec 15 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Response to Rucaparib in BRCA-Mutant Metastatic Castration-Resistant Prostate Cancer Identified by Genomic Testing in the TRITON2 Study'. Together they form a unique fingerprint.

Cite this