Only a couple of weeks after Rubraca (rucaparib) was approved for the treatment of prostate cancer, the National Comprehensive Cancer Network (NCCN) has updated its guidelines recommending this PARP inhibitor as an option for select prostate cancer patients in the U.S.
According to Clovis Oncology, which makes Rubraca, the NCCN recommends Rubraca as a “treatment option for patients with mCRPC [metastatic castration-resistant prostate cancer] and a pathogenic BRCA1 or BRCA2 mutation (…) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.”
Also, “if the patient is not fit for chemotherapy, rucaparib [Rubraca] can be considered even if taxane-based therapy has not been given,” the guidelines state.
The NCCN Clinical Practice Guidelines in Oncology are a comprehensive set of guidelines that provide detailed recommendations for the sequential management of cancer patients based on the best available evidence. They are considered the standard guide for clinical decisions and, according to the NCCN, are the most frequently updated guidelines available in any area of medicine.
The Rubraca recommendation is classified as Category 2A, meaning there is uniform consensus from the NCCN (based on lower-level evidence) that Rubraca is appropriate for the described indication. It was based on findings from the TRITON2 Phase 2 trial (NCT02952534), in which Rubraca led to promising response rates and duration of responses.
Based on these results, the treatment received conditional approval by the U.S. Food and Drug Administration (FDA) for mCRPC patients with BRCA mutations who previously received an androgen receptor inhibitor and taxane-based chemotherapy.
“We are pleased that the NCCN has acknowledged the importance of novel targeted therapies for the treatment of advanced prostate cancer, and the need for new treatment options for patients with BRCA mutations, including Rubraca, the first PARP inhibitor approved for these patients,” Patrick J. Mahaffy, president and CEO of Clovis Oncology, said in a press release.
“In particular, in the current COVID-19 environment, many patients would prefer to avoid chemotherapy, which requires frequent clinical visits, in favor of an oral agent that can be delivered directly to and taken at home,” Mahaffy added.
The ongoing TRITON2 study includes 209 men with mCRPC and mutations in genes involved in homologous recombination — a mechanism of DNA repair — including in BRCA genes. They previously had received one to two next-generation androgen receptor inhibitors and one taxane-based chemotherapy.
Results showed that of 62 patients with BRCA mutations and measurable disease, 44% responded to treatment and more than half of those responses lasted six months or longer. Also, among 115 men with BRCA mutations irrespective of measurable disease, 55% experienced meaningful reductions (by 50% or more) in their prostate-specific antigen (PSA) levels.
Treatment was overall safe and well-tolerated. The most common adverse reactions seen in BRCA-mutated patients were fatigue, nausea, anemia, transient increase in liver enzymes, decreased appetite, and constipation.
An ongoing Phase 3 trial — TRITON3 (NCT02975934) — is enrolling men with mCRPC and mutations in the most common HRR mutated genes, BRCA and ATM, to confirm the findings in TRITON2 and support a full approval of Rubraca in the U.S.
The international study is recruiting approximately 400 participants who have received one prior therapy with second-generation androgen receptor inhibitors, and will compare the benefits of Rubraca over standard care treatment with either Xtandi (enzalutamide), Zytiga (abiraterone acetate), or the chemotherapy Taxotere (docetaxel).
Rubraca is an oral treatment that works by blocking the activity of PARP enzymes, which are responsible for repairing DNA in cells. By doing so, Rubraca prevents cancer cells from fixing their DNA, ultimately causing their death. The therapy was approved initially for ovarian cancer.