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Updated: Oct 18, 2025

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

Andrea Loehr1, Akash Patnaik2, David Campbell3

  • 1Translational Medicine, Clovis Oncology, Inc., Boulder, Colorado.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 2, 2021
PubMed
Abstract

Insights

Plasma and tissue genomic testing can identify patients with BRCA-altered metastatic castration-resistant prostate cancer (mCRPC) who benefit from rucaparib treatment. This study shows similar efficacy regardless of testing method.

Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • Rucaparib is a PARP inhibitor approved for metastatic castration-resistant prostate cancer (mCRPC) with BRCA alterations.
  • Tumor tissue sequencing is standard for identifying BRCA alterations (BRCA+), but plasma profiling offers a less invasive alternative.

Purpose of the Study:

  • To evaluate the clinical efficacy of rucaparib in BRCA+ mCRPC patients identified by central plasma, central tissue, or local genomic testing.
  • To assess the concordance between plasma and tissue BRCA testing.

Main Methods:

  • TRITON2 enrolled 115 BRCA+ mCRPC patients identified via central plasma (n=34), central tissue (n=37), or local (n=44) testing.
  • Paired plasma/tissue samples were analyzed for concordance (n=38).
  • Objective response rates (ORR) and prostate-specific antigen (PSA) response rates were compared across testing groups.

Main Results:

  • Plasma/tissue concordance was 47% in patients with somatic BRCA alterations (n=19).
  • No significant differences in ORR or PSA response rates were observed between the three testing groups.
  • Patients tested solely by plasma assay showed response rates comparable to those identified by tissue testing.

Conclusions:

  • Plasma, tissue, and local genomic testing are all viable methods for identifying mCRPC patients with BRCA alterations who can benefit from rucaparib.
  • Minimally invasive plasma testing can effectively select patients for PARP inhibitor therapy when tissue is unavailable.

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