The FDA ( U.S. Food and Drug Administration ) has approved Rubraca ( Rucaparib ) tablets for the treatment of 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.
The FDA has approved this indication under accelerated approval based on objective response rate ( ORR ) and duration of response ( DOR ) data from the multi-center, single arm TRITON2 clinical trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
The FDA approval for this third indication for Rubraca is based on efficacy data from patients with mCRPC and a deleterious BRCA mutation (g ermline and/or somatic ) enrolled in 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.
Evaluable patient populations in the supplemental New Drug Application ( NDA ) dataset included the following: 62 RECIST-evaluable patients with a BRCA ( germline and/or somatic ) mutation and measurable disease ( IRR ); 115 patients with a BRCA ( germline and/or somatic ) mutation and measurable or non-measurable disease; and 209 patients with HRD-positive mCRPC enrolled in TRITON2.
The major efficacy outcomes were objective response rate and duration of response. Confirmed PSA response rate was also a prespecified endpoint. Data were assessed by independent radiologic review.
For the patients with measurable disease and a BRCA mutation, the ORR was 44%. The ORR was similar for patients with a germline BRCA mutation.
Median duration of response was not evaluable at data cutoff but ranged from 1.7 to 24+ months. Of the 27 patients with a confirmed objective response, 15 ( 56% ) patients showed a response that lasted 6 months or longer.
Additionally, a 55% confirmed prostate specific antigen ( PSA ) response rate ( 95% CI: 45, 64 ) was observed in an analysis of 115 patients with a deleterious BRCA mutation ( germline and/or somatic ) and measurable or non-measurable disease.
The safety evaluation of Rucaparib 600 mg twice daily as monotherapy treatment is based on an analysis of 209 patients with HRD-positive mCRPC from the multi-center, single arm TRITON2 clinical study, including 115 with BRCA-mutated mCRPC.
The most common adverse reactions ( greater than or equal to 20% of patients; CTCAE grade 1-4 ) occurring in the BRCA mutant population ( n=115 ) were asthenia / fatigue, nausea, anemia, ALT/AST increased, decreased appetite, constipation, rash, thrombocytopenia, vomiting, and diarrhea.
The most common laboratory abnormalities ( greater than or equal to 35% of patients; CTCAE grade 1-4 ) were increase in ALT, decrease in leukocytes, decrease in phosphate, decrease in absolute neutrophil count, decrease in hemoglobin, increase in alkaline phosphatase, increase in creatinine, increase in triglycerides, decrease in lymphocytes, decrease in platelets, and decrease in sodium.
The American Cancer Society estimates that nearly 192,000 men in the United States will be diagnosed with prostate cancer in 2020, and the GLOBOCAN Cancer Fact Sheets estimated that approximately 450,000 men in Europe were diagnosed with prostate cancer in 2018.
Castration-resistant prostate cancer has a high likelihood of developing metastases.
Metastatic castration-resistant prostate cancer, or mCRPC, is an incurable disease, usually associated with poor prognosis.
Approximately 43,000 men in the U.S. are expected to be diagnosed with mCRPC in 2020.
According to the American Cancer Society, the 5-year survival rate for mCRPC is approximately 30 %.
Approximately 12% of patients with mCRPC harbor a deleterious germline and/or somatic mutation in the genes BRCA1 and BRCA2. These molecular markers may be used to select patients for treatment with a PARP inhibitor. ( Xagena )
Source: Clovis Oncology, 2020