Dr. Alumkal on evolving PARP inhibitor paradigm in prostate cancer

In this video, Joshi Alumkal, MD, discusses the 3 FDA-approved PARP inhibitors for prostate cancer—olaparib (Lynparza), rucaparib (Rubraca), and talazoparib (Talzenna)—and what is next on the horizon for this class of agents.

Alumkal is Wicha Family Professor of Oncology, professor, Department of Internal Medicine, section head, Prostate and Genitourinary Medical Oncology, associate division chief, Basic Research, Division of Hematology-Oncology, member, the University of Michigan Rogel Cancer Center, director, Epigenetic Therapy, Michigan Center for Translational Pathology.

Video Transcript

It’s exciting that now in 2023 we have 3 FDA-approved PARP inhibitors for the treatment of our patients. Olaparib was first approved in the post–androgen receptor signaling setting in patients who have homologous recombination DNA repair defects. Results from the PROpel trial now allow us to use that drug earlier upfront with abiraterone acetate (Zytiga) in patients who are abiraterone-naive if they have BRCA1 or BRCA2alterations. Rucaparib has been around for several years. Its use is limited to patients who have castration-resistant disease that has progressed despite an androgen receptor–signaling inhibitor and docetaxel, and those patients need to have BRCA1 or BRCA2 alterations. And now we also have the approval of talazoparib with enzalutamide (Xtandi) in patients who have castration-resistant disease who are naive to enzalutamide and whose tumors harbor homologous recombination repair (HRR) gene defects. Patients do not need to have received prior docetaxel chemotherapy to receive this regimen and that's a more broad approval. And then we await the verdict on niraparib (Zejula), another PARP inhibitor that was tested in combination with abiraterone and prednisone in patients with abiraterone-naive metastatic castration-resistant prostate cancer.

So our options to treat the disease in those patients who have homologous recombination DNA repair defects have expanded substantially in the past several years. One issue to think about, particularly for the approved recent approval of olaparib based on the PROpel trial as well as for the approval of talazoparib/enzalutamide, is that those trials tested patients who were castration resistant but were naive to an androgen receptor–signaling inhibitor. Nowadays, it's common for patients to receive androgen deprivation therapy along with an androgen receptor–signaling inhibitor, whether that be abiraterone, enzalutamide, apalutamide (Erleada), or darolutamide (Nubeqa). So many of the patients who we see in clinic who develop castration resistance are already resistant to an androgen receptor–signaling inhibitor. In that group of patients, whether or not one should add a PARP inhibitor on top of the androgen receptor–signaling inhibitor the patients are already on, or whether one should stop the androgen receptor–signaling inhibitor and just treat with a single agent PARP inhibitor is unknown. And these clinical trials did not address that question, so we don't know the answer to that. And so as the landscape has shifted to early use androgen receptor–signaling inhibitors, the patient population that was tested in the pivotal talazoparib/enzalutamide and olaparib/abiraterone/prednisone trials has sort of gone away in many of our practices. And so it will be important to really think about how best to interpret those results and use those PARP inhibitors moving forward.

Transcript has been edited for clarity.