- U.S. Food and Drug Administration (FDA) (https://voice.ons.org/topic/us-food-and-drug-administration-fda)
- Oncology drug research (https://voice.ons.org/topic/oncology-drug-research)
- Prostate cancer (https://voice.ons.org/topic/prostate-cancer)
- Clinical practice (https://voice.ons.org/topic/clinical-practice)
FDA Grants Accelerated Approval to Rucaparib for BRCA-Mutated, Metastatic, Castration-Resistant Prostate Cancer
On May 15, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval (https://www.fda.gov/drugs/fda-grants-accelerated-approval-rucaparib-brca-mutated-metastatic-castration-resistant-prostate) to rucaparib (Rubraca®) for patients with deleterious BRCA mutation (germline or somatic)-associated, metastatic, castration-resistant prostate cancer (mCRPC) who had been treated with androgen receptor-directed therapy and taxane-based chemotherapy.
Efficacy was investigated in an ongoing, multicenter, single-arm clinical trial (TRITON2; NCT02952534) of 115 patients with BRCA-mutated (germline or somatic) mCRPC who had been treated with androgen receptor-directed therapy and taxane-based chemotherapy. Patients received rucaparib 600 mg orally twice daily and concomitant gonadotropin-releasing hormone (GnRH) analog or had prior bilateral orchiectomy.
Investigators assessed objective response rate (ORR) and duration of response (DOR) in 62 patients with measurable disease. Confirmed ORR was 44% (95% CI = 31, 57). Median DOR was not evaluable (95% CI = 6.4, not evaluable). The range for DOR was 1.7 to over 24 months. Fifteen of the 27 patients with confirmed objective responses (56%) had DOR of greater than or equal to six months.
The most common adverse reactions (≥ 20%) were fatigue, nausea, anemia, increased ALT/AST, decreased appetite, rash, constipation, thrombocytopenia, vomiting, and diarrhea.
The recommended rucaparib dose is 600 mg orally twice daily with or without food. Patients receiving rucaparib for mCRPC should also receive a GnRH analog concurrently or should have had bilateral orchiectomy.
FDA granted the indication accelerated approval based on ORR and DOR. Continued approval for the indication may be contingent on verification and description of clinical benefit in confirmatory trials.
FDA previously granted rucaparib breakthrough therapy designation for the indication. The application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).