Rubraca (rucaparib), Clovis Oncology‘s PARP inhibitor, shrank tumors in 44% of metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA mutations included in a Phase 2 clinical trial, the company announced.
The treatment, which already is approved for ovarian cancer, also reduced PSA levels — a biomarker of prostate cancer — in 51.1% of patients with BRCA mutations.
The findings were presented recently at the European Society of Medical Oncology (ESMO) 2018 Congress by Wassim Abida, a medical oncologist at the Memorial Sloan Kettering Cancer Center, and principal investigator for the Phase 2 study.
The poster was titled “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.”
Nearly 12% of men with mCRPC have a mutation in the BRCA1 or BRCA2 genes, which play key roles in repairing errors in the DNA. These tumors are more susceptible to further DNA damage, and often respond well to treatments that block other proteins involved in DNA damage repair.
“Rubraca has previously demonstrated antitumor activity in its approved indications for women with advanced ovarian cancer,” Abida said in a press release. “These new data show that Rubraca may also offer a new approach for the treatment of mCRPC associated with BRCA1 and BRCA2 alterations, with the potential to achieve a clinical response in patients with few remaining therapy options.”
The trial included 85 mCRPC patients who had received at least one treatment blocking the androgen receptor and one taxane-based chemotherapy, and who had an inherited or acquired mutation in BRCA genes or in one of the 13 DNA repair genes known to increase susceptibility to PARP inhibitors.
Depending on their disease and mutation status, patients were divided in three groups: those with BRCA or ATM mutations and with measurable disease; those with BRCA or ATM mutations without measurable disease; and those with mutations in other DNA repair genes, with or without measurable disease.
The study’s primary objectives were to determine overall response rates in patients with measurable disease, and the proportion of patients without measurable disease who saw a reduction in the PSA levels after treatment.
Secondary goals included duration of response, time to disease progression or death, overall survival, and safety measures.
After a median follow-up of 5.7 months, 46 patients were evaluable for responses. Among the 25 patients with BRCA mutations, 44% had seen their tumor shrink, after only a median of 3.7 months on treatment. At the time of the analysis, more than half of patients were still responding to Rubraca.
The results also showed that 51.1% of patients with BRCA mutations saw a reduction in their PSA levels.
The most common adverse events were fatigue, nausea, anemia, and constipation. Five patients discontinued Rubraca due to a treatment-related adverse effect, and one patient died of disease progression.
Findings from the trial have led the U.S. Food and Drug Administration to grant breakthrough therapy designation to Rubraca as a treatment for mCRPC patients with BRCA mutations, earlier this month.
“We are very encouraged by these initial findings from the TRITON2 study, which demonstrate the potential of Rubraca to treat men with advanced prostate cancer whose disease has progressed after receiving multiple prior lines of therapy,” said Patrick J. Mahaffy, president and CEO of Clovis Oncology.
“PARP inhibitors are now a validated therapeutic class in oncology in multiple tumor types, and these new data underscore the benefit that Rubraca may provide for men with advanced, BRCA-mutant castration-resistant prostate cancer,” Mahaffy added. “Having recently received Breakthrough Therapy designation based on these data, we are committed to the rapid development of Rubraca for men with this very difficult-to-treat disease.”