FDA Approves Rucaparib for BRCA+ mCRPC


The FDA has approved rucaparib for the treatment of adult patients with BRCA-mutant recurrent, metastatic castration-resistant prostate cancer.

The FDA has granted rucaparib (Rubraca) an accelerated approval for the treatment of adult patients with 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.1

“Standard treatment options for men with mCRPC have been limited to androgen receptor-targeting therapies, taxane chemotherapy, radium-223 and sipuleucel-T,” Wassim Abida, MD, principal investigator of TRITON2 and medical oncologist, Memorial Sloan Kettering Cancer Center, stated in a press release. “Rubraca is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation. Given the level and duration of responses observed with Rubraca in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”

In the international, multicenter, open-label TRITON2 study, investigators enrolled male patients with mCRPC associated with 1 of 13 homologous recombination repair (HRR) gene alterations. Patients had disease progression on androgen receptor—directed therapy and 1 prior taxane-based chemotherapy. Additionally, they had an ECOG performance status of 0 or 1 and could not have received a prior PARP inhibitor, mitoxantrone, cyclophosphamide, or platinum-based chemotherapy.2

Patients were treated with rucaparib at 600 mg twice daily until radiographic progression or treatment discontinuation. Tumors were radiographically assessed every 8 weeks for 24 weeks, and then every 12 weeks. Prostate-specific antigen (PSA) assessments were performed every 4 weeks.

The primary end points of the trial include confirmed ORR per RECIST/Prostate Cancer Clinical Trials Working Group 3 criteria in patients with measurable disease at baseline and PSA response in patients with no measurable disease at baseline.

The evaluable population for PSA response included 45 patients with BRCA1/2 mutations, and the population evaluable for radiographic response included 25 patients with BRCA1/2 mutations.

The median age of the evaluable 45 patients with BRCA1/2 mutations was 71 years (range, 50-88); most (62.2%) had an ECOG performance status of 1. Prior therapies included abiraterone acetate (Zytiga; 55.6%), enzalutamide (Xtandi; 73.3%), both abiraterone and enzalutamide (31.1%), docetaxel (95.6%), cabazitaxel (Jevtana; 8.9%), sipuleucel-T (Provenge; 13.3%), and radium-223 dichloride (Xofigo; 11.1%).

A total of 88.9% of patients with BRCA1/2 mutations had bone metastases, 62.2% had nodal metastases, and 42.2% had visceral metastases. Additionally, 33.3% of patients had a germline BRCA1/2 mutation and 66.7% had a somatic BRCA1/2 mutation.

The preliminary results included data from 85 patients enrolled through June 29, 2018, with a median follow-up of 5.7 months (range, 2.6-16.4). These data showed that rucaparib demonstrated a 44% confirmed ORR (95% CI, 24.4%-65.1%) by investigator assessment among evaluable men with BRCA1/2-mutated mCRPC. Among those with BRCA1/2 alterations, 51.1% had a confirmed PSA response to rucaparib.

All 11 investigator-assessed radiographic responses in the patients with BRCA-mutated tumors were partial responses (PRs); 9 patients (36.0%) had stable disease. The median duration of response had not been reached.

Updated findings were presented at the 2019 ESMO Congress, with a median follow-up of 13.1 months (range, 4.1-28.5).3 Results showed that rucaparib elicited a 43.9% confirmed ORR and a confirmed PSA response of 52.0% in patients with mCRPC and a BRCA1/2 mutation. Responses were durable, with 60% of responses lasting ≥24 weeks.

Regarding safety, all-grade treatment-emergent adverse events occurring in >20% of patients were asthenia/fatigue (55.3%), nausea (49.5%), anemia/decreased hemoglobin (37.9%), decreased appetite (27.9%), transient increased aspartate transaminase/alanine aminotransferase (24.7%), constipation (24.7%), vomiting (22.1%), and diarrhea (21.1%).

The accerated approval of rucaparib in this setting is contingent on the results of a confirmatory trial. The ongoing, multicenter, randomized phase 3 TRITON3 trial (NCT02975934) is comparing single-agent rucaparib with physician’s choice of abiraterone acetate, enzalutamide, or docetaxel in men with mCRPC and homologous recombination deficiency whose disease has progressed on prior treatment.

Rubraca was previously approved as monotherapy for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a CR or PR to platinum-based chemotherapy. It is also approved for the treatment of patients with deleterious BRCA mutation—germline and/or somatic—associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥2 chemotherapies and selected for therapy based on an FDA-approved companion diagnostic.


  1. Rubraca® (Rucaparib) Approved In The U.S. As Monotherapy Treatment For Patients With BRCA1/2-Mutant, Metastatic Castration-Resistant Prostate Cancer (MCRPC) Who Have Been Treated With Androgen Receptor-Directed Therapy And A Taxane-Based Chemotherapy.Published May 15, 2020. https://bit.ly/2z0rMrK. Accessed May 15, 2020.
  2. Clovis Oncology highlights Rubraca (rucaparib) updated data from the ongoing TRITON2 clinical trial in patients with mCRPC and exploratory and integrated analyses in recurrent ovarian cancer at the ESMO Congress 2019 [news release]: Boulder, CO. Clovis Oncology, Inc. Published September 29, 2019. https://bit.ly/2u4iEPS. Accessed January 15, 2020.
  3. Abida W, Bryce AH, Vogelzang NJ, et al. Preliminary results from TRITON2: a phase 2 study of rucaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination repair (HRR) gene alterations. Ann Oncol. 2018;29(suppl_8):viii271-viii302. doi: 10.1093/annonc/mdy284

The approval is based on findings from the ongoing phase II TRITON2 trial (NCT02952534), in which the PARP inhibitor induced a 44% confirmed objective response rate (ORR) in 62 evaluable patients with BRCA1/2-mutant mCRPC.

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