Key clinical point: Rucaparib is well tolerated and shows good response in patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious BRCA alteration.

Major finding: The overall response rate, complete response, and partial response were 3.5%, 11.3%, and 32.3%, respectively, in the independent radiology review and 50.8%, 6.2%, and 44.6%, respectively, in the investigator assessment. The most frequent grade 3 or higher treatment-emergent adverse event was anemia (25.2%).

Study details: The data come from the open-label non-comparator phase 2 TRITON2 trial involving 115 patients with mCRPC and a deleterious BRCA alteration treated with rucaparib.

Disclosures: The study was funded by Clovis Oncology. SP Watkins, D Despain, AD Simmons, A Loehr, M Dowson, T Golsorkhi, and S Chowdhury are employees of Clovis Oncology. The authors reported relationships with multiple pharmaceutical companies, including Clovis Oncology.

Commentary

“The identification of mutations in proteins involved in DNA damage repair (DDR) in prostate cancer has led to numerous studies focused on targeting this pathway in prostate cancer. Inhibitors of poly(ADP-ribose) polymerase (PARP) can induce synthetic lethality in tumors with DDR mutations. In the phase II Triton-2 study, patients with who had failed one or two androgen receptor-directed therapies and a taxane were treated with the PARP inhibitor rucaparib. In this report, only patients with germline or somatic alterations in BRCA1 or BRCA2 were included. The overall response rate (per independent radiologist review) was 43.5% in patients who received rucaparib, while the PSA response rate was 54.8%. Overall survival data were not mature at the time of publication. This study provides additional evidence that PARP inhibitors are effective in this subset of prostate cancer.”

Mark Klein, MD
Disclosure: Dr. Klein was a local site investigator for this study.