Clin Cancer Res. 2021 Oct 1:clincanres.2199.2021. doi: 10.1158/1078-0432.CCR-21-2199. Online ahead of print.
ABSTRACT
PURPOSE: The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is approved in the US 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 BRCA+ mCRPC patients identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2.
EXPERIMENTAL DESIGN: 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 BRCA+ patients 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 three assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different to patients identified as BRCA+ by tissue testing.
CONCLUSION: 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.
PMID:34598946 | DOI:10.1158/1078-0432.CCR-21-2199
