Rucaparib Demonstrates Antitumor Activity in Men with BRCA-mutated mCRPC

Rucaparib (Rubraca, Clovis Oncology) demonstrated promising antitumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious BRCA alteration, according to results of a study published online in the Journal of Clinical Oncology (Abida W, et al. J Clin Oncol. 2020 Aug 14. Epub ahead of print.).

BRCA1 and BRCA2 alterations are common in men with mCRPC and may confer sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. In the international, open-label TRITON2 clinical trial, researchers assessed the PARP inhibitor rucaparib for the treatment of men with mCRPC and a deleterious alteration in a DNA-damage response gene who had progressed after 1 or 2 lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy.

Patnaik and colleagues analyzed 115 men (median age, 72 years; range, 50-88; 73.9% white) in the trial who had a BRCA1 (N = 13) or BRCA2 (N = 102) alteration with or without measurable disease and received at least 1 dose of rucaparib.

The primary end point of the study was objective response rate (ORR), and secondary end points included duration of response for radiographic response, locally assessed prostate-specific antigen (PSA) response rate, time to PSA progression, radiographic progression-free survival, overall survival (OS), and safety. Median follow-up was 17.1 months (range, 7.6-31.5).

Results showed an ORR of 43.5 (per independent radiology review) and 50.8% (per investigator assessment), with a confirmed PSA response rate of 54.8%.

ORRs appeared similar for patients with a germline or somatic BRCA alteration and those with a BRCA1 or BRCA2 alteration. Higher PSA response rates were observed among men with BRCA2 alterations.

Median time to PSA progression was 6.5 months. Median radiographic progression-free survival was 9 months (per independent radiology review) and 8.5 months (per investigator assessment). OS data at the time of the analysis remained immature, with 12-month OS estimated at 73%.

The safety profile of rucaparib appeared consistent with that observed in other solid tumor types, the researchers noted.

“There is a critical need for personalized medicines to effectively treat advanced prostate cancer,” said Akash Patnaik, MD, PhD, MMSc, Assistant Professor of Medicine, Hematology/Oncology, The University of Chicago, IL, and one of the study authors, in a press release. “Approximately 12% of [patients with advanced prostate cancer] have tumors that harbor a BRCA1 or BRCA2 alteration. We have arrived at an exciting inflection point in the field, as we now have the first FDA-approved targeted therapy that can effectively treat a genetically defined subset of patients with metastatic castration-resistant prostate cancer with a poor prognosis and worse clinical outcomes on conventional treatments.”

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