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

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 next-generation 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.
(©2021 American Association for Cancer Research.)