Rubraca (rucaparib) - 2 indications

Scroll down for additional information on each indication:

• for the treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer; approved December 2016
• for the treatment of adults with previously treated deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer; approved May 2020

General Information

Rubraca (rucaparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor.

Rubraca is specifically indicated for the following:

• as a maintenance treatment for adults with ovarian cancer, fallopian tube cancer, or primary peritoneal cancer whose cancer has come back and who are in response (complete or partial response) to a platinum-based chemotherapy.
• for adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. 

Rubraca is supplied as a tablet for oral administration. The recommended dose is 600 mg orally twice daily with or without food. Treatment should be continued until disease progression or unacceptable toxicity. Patients with mCRPC should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

Mechanism of Action

Rubraca (rucaparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor; PARP's play a role in DNA repair. In vitro studies have shown that rucaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death. Increased rucaparib-induced cytotoxicity was observed in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes. Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA.

Side Effects

Adverse effects associated with the use of Rubraca may include, but are not limited to, the following:

• nausea
• fatigue (including asthenia)
• vomiting
• anemia
• abdominal pain
• dysgeusia
• constipation
• decreased appetite
• diarrhea
• thrombocytopenia
• dyspnea
• laboratory abnormalities 

Indication 1 - for the treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer

approved December 2016

Clinical Trial Results

The FDA granted accelerated approval to Rubraca for ovarian cancer based on two multicenter, single-arm, open-label clinical trials, Study 1 and Study 2, in 106 patients with advanced BRCA-mutant ovarian cancer who had progressed after 2 or more prior chemotherapies. All 106 patients received Rubraca 600 mg orally twice daily as monotherapy until disease progression or unacceptable toxicity. Objective response rate (ORR) and duration of response (DOR) were assessed by the investigator and independent radiology review (IRR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Objective Response Rate was 54%, with a Complete Response of 9%, Partial Response of 45% and Median DOR of 9.2 months. Response assessment by independent radiology review was 42%, with a median DOR of 6.7 months. Investigator-assessed ORR was 66% in platinum-sensitive patients, 25% in platinum-resistant patients, and 0% in platinum-refractory patients. ORR was similar for patients with a BRCA1 gene mutation or BRCA2 gene mutation.

Indication 2 - for the treatment of adults with previously treated deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer

approved May 2020

Clinical Trial Results

The FDA approval of Rubraca for prostate cancer was based on objective response rate (ORR) and duration of response (DOR) data from the multi-center, single arm TRITON2 clinical trial. The major efficacy outcomes are confirmed ORR and DOR by modified RECIST version 1.1/PCWG3 criteria assessed by blinded independent radiologic review (IRR). Confirmed prostate-specific antigen (PSA) response rate is an additional prespecified endpoint. Data showed a 44% ORR (N=62) by blinded-IRR assessment. Objective response rates were similar for patients with a germline BRCA versus somatic BRCA mutation. Median DOR by blinded-IRR assessment was not evaluable (NE) at data cut-off. Additionally, a 55% confirmed prostate specific antigen (PSA) response rate was observed in an  analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or non-measurable disease.