Rucaparib Sparks Major Change in the Prostate Cancer Space

Until the recent FDA approval of rucaparib (Rubraca) for BRCA-mutant metastatic castration-resistant prostate cancer (mCRPC), this patient population had no biomarker-driven therapies. But now the accelerated approval will bring a sea change to the prostate cancer space, while stressing the importance of genetic testing for men with high-risk and metastatic disease, according to Alan Bryce, MD.

Bryce recently sat down with Oncology Nursing News’ sister publication, OncLive, and discussed how the PARP inhibitor rucaparib is transforming the field.

“This is an important moment in prostate cancer in that we finally have the fist approval for a biomarker-selected targeted therapy,” Bryce said. “We’ve known for some time that BRCA1/2 mutations in prostate cancer are predictors for efficacy to PARP inhibitors. Multiple studies have shown that. Now, we have [data] which led to the FDA approval of the PARP inhibitor rucaparib for use in patients with BRCA1/2-mutatnt mCRPC.”

Adverse Events of Rucaparib

TRITON2, the phase II trial that led to the approval, showed that rucaparib had a 44% confirmed objective response rate (ORR) in 62 evaluable patients with BRCA-mutant mCRPC who had prior androgen receptor-directed therapy and taxane-based chemotherapy. And while these results are promising, there are still adverse events (AEs) that nurses should look out for.

The most common AEs were asthenia/fatigue, nausea, anemia/decreased hemoglobin, decreased appetite, transient increased aspartate transaminase/alanine aminotransferase, constipation, vomiting, and diarrhea. The toxicity profile was not different to what is typically seen in patients with breast or ovarian cancer who are on rucaparib.

There is one key AE that clinicians should be aware of. “The main toxicity is anemia,” Bryce said. “Prolonged use of a PARP inhibitor can certainly cause some myelosuppression. You can see the blood counts drop.”

“However, it’s fairly well tolerated and consistent with what oncologists already know from their use in patients with breast and ovarian cancer.”

Genetic Testing Is Crucial

NCCN guidelines already call for germline testing in every patient with high-risk, very high-risk, or metastatic prostate cancer. But somatic testing will become more important, too.

“Somatic mutation are the private mutations in the cancer cells themselves,” Bryce explpained. “PARP inhibitors have utility in patients with germline or somatic mutations. In the setting of any high-risk, very high-risk, or metastatic prostate cancer, patients should have germline testing to inform themselves and their family.”

Bryce also emphasized the importance of getting both types of genetic testing.

“Secondly, in the context of treatment decisions, somatic testing needs to be done on top of germline testing. It’s really not one or the other. At least half of patients will only have mutations in their tumor and not in their germline.”

TRITON3 and Beyond

Rucaparib’s approval is contingent on results from the TRITON3 trial evaluating patients who were not previously treated with chemotherapy, pushing the PARP inhibitor to earlier in the treatment regimen.

“We expect to see the [same] drug development with rucaparib as we see with every other cancer drug in which it starts in the late-stage setting and is marched forward in the treatment paradigm,” Bryce said. “TRITON3 is moving [rucaparib] further forward.”