NEW YORK – The US Food and Drug Administration has approved Clovis Oncology's rucaparib (Rubraca) for men with BRCA1/2-mutated, metastatic castration-resistant prostate cancer who have previously received androgen receptor-directed therapy and taxane-based chemotherapy.
The agency granted accelerated approval based on the single-arm TRITON2 study, involving 62 patients with a germline or somatic BRCA mutation and measurable disease; 115 BRCA-mutated patients with measurable or non-measurable disease; and 209 patients with homologous recombination deficiency. Clovis collaborated with Foundation Medicine to use a next-generation sequencing panel to identify patients in this study with alterations in BRCA1/2, ATM, and in 13 other genes indicating homologous recombination deficiency.
The objective response rate was 44 percent, and responses were similar regardless of whether patients had somatic or germline BRCA1/2 mutations. The median duration of response was not reached by the data cut-off, but patients who saw their tumors shrink continued to respond to the drug for at least six months.
Researchers also measured prostate-specific antigen as another indicator of drug response. The PSA response rate was 55 percent among the 115 BRCA-mutated patients with measurable and non-measurable disease.
The safety of rucaparib was evaluated in 209 patients with HRD-positive metastatic, castration-resistant prostate cancer and 115 patients with BRCA-mutated disease. Patients, particularly those with BRCA mutations, commonly experienced asthenia/fatigue, nausea, anemia, and elevated liver tests. The drug carries warnings for myelodysplastic syndrome, acute myeloid leukemia, and embryo-fetal toxicity.
There are limited treatment options for patients with metastatic castration-resistant prostate cancer, including androgen receptor-targeting therapies, taxane chemotherapy, Radium-223 and sipuleucel-T.
"The FDA approval of Rubraca is a significant milestone for patients with metastatic castration-resistant prostate cancer and a deleterious BRCA mutation," Howard Soule, executive VP and chief science officer of the Prostate Cancer Foundation, said in a statement. "Although new treatments for prostate cancer have been approved in recent years, most men living with advanced stages of this disease continue to face a difficult journey with few treatment options."
Since FDA granted accelerated approval in this indication, Clovis will have to provide confirmation of rucaparib's benefit in this setting in the TRITON3 study.