FDA Approved Two PARP Inhibitors for Prostate Cancer

by Angela Maas

Although poly ADP-ribose polymerase (PARP) inhibitors are not new to the market, two of them recently gained approval for use in prostate cancer for the first time. The therapies will bring a new option for the treatment of certain subpopulations of patients.

On May 19, the FDA expanded the label of AstraZeneca and Merck & Co., Inc.'s Lynparza (olaparib) to include the treatment of people with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer who have progressed following treatment with Xtandi (enzalutamide) or Zytiga/Yonsa (abiraterone acetate).

On May 15, the FDA gave accelerated approval to Clovis Oncology, Inc.'s Rubraca (rucaparib) for the treatment of adults with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.

Two other PARP inhibitors — GSK’s Tesaro, Inc.'s Zejula (niraparib) and Pfizer Inc.'s Talzenna (talazoparib) — are on the market, and both are in clinical trials for prostate cancer.

Lynparza's and Rubraca's approvals are "indicative of the growing knowledge we are gaining with respect to the intermediary pathways within the cells regulating DNA repair as it relates to tumor growth," says Winston Wong, Pharm.D., president of W-Squared Group.

The PARP inhibitors will impact "refractory patients who have failed standard-of-care therapies," notes Mesfin Tegenu, R.Ph., president of PerformRx, LLC. First-line treatment will be with antiandrogens or taxanes, he explains: Zytiga, Yonsa, Jevtana (cabazitaxel), Taxotere (docetaxel) or Xtandi. Then the top competitors in the second-line setting will be Lynparza, Rubraca and Keytruda (pembrolizumab), he says.

Asked how the two PARP inhibitors compare with other therapies in the class, Tegenu points out that "Lynparza had higher objective response rates and better radiographic progression-free survival compared to enzalutamide and abiraterone. It also showed benefit compared to docetaxel. Men with specific mutations may benefit more with PARP inhibitors."

"Rubraca after receiving taxane therapy showed benefit," he continues. "It is currently being compared to abiraterone, enzalutamide or docetaxel in an ongoing clinical trial. It has accelerated approval contingent upon verification of success in this trial.

From RADAR on Specialty Pharmacy