Rucaparib Demonstrates Significant Antitumor Activity for Patients with Advanced Prostate Cancer

The targeted therapy, rucaparib (Rubraca), can successfully treat patients with advanced prostate cancer who have mutated BRCA1/BRCA2 genes, according to a study published in the Journal of Clinical Oncology.

Specifically, rucaparib demonstrated antitumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC) while maintaining a safety profile consistent with previously reported studies on other solid tumor types.¹

“There is a critical need for personalized medicines to effectively treat advanced prostate cancer,” said one of the study authors Akash Patnaik, MD, PhD, UChicago Medicine, in a press release.² “Approximately 12% of advanced prostate cancer patients 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 mCRPC patients, with poor prognosis and worse clinical outcomes on conventional treatments.”

Objective response rates (ORRs), according to independent radiology review and investigator assessment, were 43.5% (n = 27; 95% CI, 31.0%-56.7%) and 50.8% (n = 33; 95% CI, 38.1%-63.4%), respectively. More, the prostate-specific antigen (PSA) response rate was 54.8% (n = 63; 95% CI, 45.2%-64.1%).

ORRs for both patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration were similar. The most frequent grade 3 or worse adverse event for patients was anemia (n = 29; 25.2%).

The research included 115 patients with a BRCA alteration with or without measurable disease. Patients who progressed after 1 to 2 lines of next-generation androgen receptor–directed therapy were enrolled in the study.

“In a separate publication, we have demonstrated that additional non-BRCA1/2 mutations within the DNA repair pathway in mCRPC patients could confer sensitivity or resistance to PARP inhibitor rucaparib," Patnaik said. "We still have a lot more to learn about which patients with additional genetically defined alterations in the DNA repair pathway will benefit most from this therapy.”

Primary end points for the study were ORR and locally assessed PSA response rate.

Based on the data from TRITON2, the FDA granted rucaparib accelerated approval in May. The findings from this study were presented in February 2020 at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology in San Francisco.

“Studies are underway within our laboratory and clinical trials to test combinations of PARP inhibitors with other conventional or experimental therapies to substantially increase the fraction of mCRPC patients that respond to PARP inhibitors,” Patnaik said. “Based on these investigations, we are optimistic about the development of additional personalized treatment options for our mCRPC patients.”

References:

1. Abida W, Patnaik A, Campbell D, et al. Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. Journal of Clinical Oncology. DOI: 10.1200/JCO.20.01035.

2. PARP inhibitor becomes new treatment option for some men with advanced prostate cancer [news release]. Published August 14, 2020. https://www.newswise.com/articles/parp-inhibitor-becomes-new-treatment-option-for-some-men-with-advanced-prostate-cancer?sc=sphr&xy=10021790. Accessed September 29, 2020.