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

Abstract

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 <i>BRCA1</i> or <i>BRCA2</i> (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 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. TRITON2 enrolled 115 patients with BRCA⁺ identified by central plasma (<i>n</i> = 34), central tissue (<i>n</i> = 37), or local (<i>n</i> = 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. 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.