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Higano Examines Emerging Role of PARP Inhibitors in mCRPC

Brandon Scalea
Published: Tuesday, Apr 02, 2019

Celestia Higano, MD
Celestia Higano, MD
PARP inhibitors have not made the same headway in metastatic castration-resistant prostate cancer (mCRPC) as they have in ovarian and breast tumors, but recent data suggest that the class of drugs could play a role in patients with mCRPC who have certain DNA repair defects, said Celestia Higano, MD.

For example, preliminary data from the phase II single-arm TRITON2 trial showed that treatment with rucaparib (Rubraca) resulted in a 44% confirmed objective response rate (ORR) by investigator assessment in patients with mCRPC who harbor BRCA1/2 mutations.1 There was also a 51% confirmed prostate-specific antigen response in those who received the PARP inhibitor.

Based on these positive findings, the FDA granted a breakthrough therapy designation to rucaparib in October 2018 for the treatment of patients with BRCA1/2-mutated mCRPC. The phase III TRITON3 trial (NCT02975934), which will compare rucaparib with physician’s choice of therapy in this patient population, is currently accruing.

In addition, data from the ongoing phase II GALAHAD trial (NCT02854436) presented at the 2019 Genitourinary Cancers Symposium suggested that single-agent niraparib (Zejula) could be a beneficial option for patients with biallelic BRCA1/2 mutations. In the study, the composite response rate in those who received the agent was 62.1%, and the ORR was 37.5%.2

In an interview with OncLive, Higano, a member of the Clinical Research Division at Fred Hutchinson Cancer Research Center and a professor in the Department of Medicine and Urology at the University of Washington and Seattle Cancer Care Alliance, discussed the potential for PARP inhibitors in patients with mCRPC, as well as the role of darolutamide in nonmetastatic disease.

OncLive: What data supported the emergence of PARP inhibitors in prostate cancer?

Higano: The interesting thing is that we've seen some scant, very intriguing data in prostate cancer. There are a lot more data with PARP inhibitors in other cancers. However, in prostate cancer, we first became sensitized to the importance of PARP inhibitors in a study that was published several years ago in the New England Journal of Medicine. In that study, they found a very high response rate—approximately 88%—in patients who had DNA repair defects compared with those who did not. That particular study really got our attention and, all of a sudden, opened the door for PARP inhibitors in prostate cancer.

What percentage of patients with prostate cancer have DNA repair defects?

It's not common, but it's not that rare either. As a matter of fact, there are more people with these DNA repair problems than we previously appreciated. One of the reasons is that we were just looking at the tissue of patients who were diagnosed with early-stage prostate cancer. In that case, there was a smaller percentage.

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