Rucaparib active in BRCA-mutated metastatic castration-resistant prostate cancer
Click Here to Manage Email Alerts
Rucaparib demonstrated antitumor activity among men with metastatic castration-resistant prostate cancer and a deleterious BRCA alteration, according to results of the phase 2 TRITON2 study published in Journal of Clinical Oncology.
Safety of rucaparib (Rubraca, Clovis Oncology), a poly(ADP-ribose) polymerase (PARP) inhibitor, appeared consistent with that observed in other solid tumor types, researchers noted.
“There is a critical need for personalized medicines to effectively treat advanced prostate cancer,” Akash Patnaik, MD, PhD, MMSc, assistant professor of medicine in the hematology/oncology section of the department of medicine at The University of Chicago, said 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.”
Androgen receptor-directed therapy, taxane chemotherapy and other treatments have improved outcomes for men with metastatic castration-resistant prostate cancer. However, most of these men eventually experience disease progression, and subsequent treatment options are limited.
The international, open-label TRITON2 trial assessed rucaparib for treatment of men with metastatic castration-resistant prostate cancer and a deleterious alteration in a DNA-damage response gene who had progressed after one or two 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 one dose of rucaparib.
Objective response rate served as the study’s primary endpoint. Secondary endpoints included duration of response for radiographic response, locally assessed PSA response rate (50% or greater decrease from baseline), time to PSA progression, radiographic PFS, OS and safety.
Median follow-up was 17.1 months (range, 7.6-31.5).
Results showed an ORR of 43.5% (95% CI, 31-56) per independent radiology review and 50.8% (95% CI, 38.1-63.4) per investigator assessment, with a confirmed PSA response rate of 54.8% (95% CI, 45.2-64.1).
ORRs appeared similar for men with a germline or somatic BRCA alteration and for men with a BRCA1 or BRCA2 alteration. Researchers observed higher PSA response rates among men with BRCA2 alterations.
Median time to PSA progression was 6.5 months (95% CI, 5.9-7.8).
Median radiographic PFS was 9 months (95% CI, 8.3-13.5) per independent radiology review and 8.5 months (95% CI, 8.1-11.2) per investigator assessment. OS data at the time of the analysis remained immature, with 12-month OS estimated at 73% (95% CI, 62.9-80.7).
The most common grade 3 or higher adverse event was anemia (25.2%).
Based on these results, the FDA granted accelerated approval to rucaparib in May for treatment of men with BRCA-mutated metastatic castration resistant prostate cancer.
“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,” Patnaik said in the release. “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 patients with [metastatic castration-resistant prostate cancer who] respond to PARP inhibitors.”
Collapse
Click Here to Manage Email Alerts