PARP Inhibitors in Prostate Cancer - Episode 10

Systemic Treatment Options for Metastatic Castration-Resistant Prostate Cancer

Dr Morgans examines systemic treatment options for patients with metastatic castration-resistant prostate cancer.

Matthew Fowler: Could you talk a little about some of the systemic treatment options for this disease?

Alicia Morgans, MD, MPH: Metastatic castration-resistant prostate cancer [mCRPC] has become incredibly complex over the last few years in terms of its treatment options. Before I get into the specific options, I want to emphasize that 1 of the main purposes of our treatment plan for men with prostate cancer is that, while continuing an ADT [androgen deprivation therapy] backbone at all times, we want to change the mechanism of action in most cases of the treatment that we combine with our ADT to target evolving mutations that may give patients’ cancers resistance to the prior therapy that they may have seen in their last treatment.

Importantly, when we think about what we’re doing in mCRPC, we typically want to use a different approach from what we used in combination with ADT in the metastatic hormone-sensitive situation. For patients who received an androgen receptor [AR]–targeted agent in combination with ADT in the metastatic hormone-sensitive setting, we typically want to change to some other approach, whether it’s chemotherapy, immunotherapy with something like sipuleucel-T, something like radium for patients who have bone-only metastatic disease, or a PARP inhibitor for patients who have specific DNA-repair defect alterations. We want to change that mechanism of action rather than use another AR-targeted agent.

In the metastatic CRPC [castration-resistant prostate cancer] setting, if patients have had chemotherapy in combination with their ADT for their hormone-sensitive disease or have only had ADT, we can use things like abiraterone acetate and prednisone or enzalutamide in the mCRPC setting, because those are the 2 androgen receptor–targeted agents approved for mCRPC. Other than that, we have pembrolizumab for patients who have MSI [microsatellite instability]–high status or, as I mentioned, olaparib or rucaparib for patients who have DNA-repair defect alterations. These are slightly different indications that we can get into shortly.

This transcript has been edited for clarity.