Shore Highlights Ongoing Efforts With PARP Inhibitors, Radioligand Therapy in Prostate Cancer

Neal Shore, MD, FACS

Attempts to expand the current prostate cancer armamentarium through the development of novel, targeted therapies are vital for moving the paradigm forward and ultimately improving patient outcomes, according to Neal Shore, MD, FACS.

In an interview with OncLive®, Shore highlighted ongoing research and continuing conversations regarding the use of PARP inhibitors and targeted radiopharmaceuticals within prostate cancer. This included new data with 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer (mCRPC), PARP inhibitors and radioligand therapies that comprise the current armamentarium in mCRPC and metastatic castration-sensitive prostate cancer (mCSPC), and ongoing efforts to reduce or reverse androgen receptor (AR) resistance using CDK4/6 inhibition.

Additionally, Shore provided further insights on the recent FDA approval of enzalutamide (Xtandi) for patients with high-risk, biochemically recurrent nonmetastatic CSPC.

Shore is the US chief medical officer of Surgery and Oncology at GenesisCare USA, and the medical director of the Carolina Urologic Research Center in Myrtle Beach, South Carolina.

OncLive: What current or ongoing research on radioligand therapy in prostate cancer are you most excited about?

Shore: There are so many amazing things going on in the world of prostate cancer research. Recently, we reported on a big phase 3 trial of 177Lu-PSMA-617 radioligand therapy, specifically in patients who had not received chemotherapy, had castration-resistant disease, and had progressed on an AR inhibitor. That study met its primary end point of radiographic progression with a hazard ratio of 0.43.

We're following those patients for survival benefit as well. We already had demonstrated survival and radiographic progression benefit in post-chemotherapy mCRPC. Typically, we look at the patients who are at the far right of the continuum of advanced disease. We want to look at them earlier or more proximal in the prostate cancer continuum.

There are other radiopharmaceuticals being investigated in this space. This is very important for our urologic oncology and medical oncology colleagues as we try to continue to offer [more choices for] patients, whether that's a chemotherapy [agent] or radiopharmaceuticals.

How would you define the current landscape of PARP inhibitors and radiopharmaceuticals in metastatic prostate cancer?

We already have radium-223 dichloride [Xofigo] as [a viable option in mCRPC]. For our patients who have homologous recombination repair [HRR] mutations, particularly BRCA mutations, we have PARP inhibitors. The [phase 3] PROpel [NCT03732820], TALAPRO-2 [NCT03395197] and MAGNITUDE [NCT03748641] trials offer the opportunity for [PARP inhibitor] combinations in that space as well.

Moving into the castration-sensitive arena, we are looking at both radiopharmaceuticals and HRR drugs for all-comer populations of patients who have metastatic disease. This is [another] exciting area in the field, [and includes] some of the work that my clinical research site is focusing on.

Could you expand on ongoing efforts to address the development of AR-targeted resistance in prostate cancer?

[This is another large] area of research. There is some exciting work being done with CDK4/6 inhibitors, [such as] adding them to abiraterone acetate [Zytiga] to try and thwart resistance to the AR pathway. EZH2 pathway–targeted drugs and degrader drugs that can work to also further delay resistance are very exciting. Some additional work on depo formulations of abiraterone in the form of a 90-day intramuscular formulation [is being conducted]. Overall, there's a lot of excitement within [research] to address the development of resistance to AR pathway drugs.