Dana E. Rathkopf, MD, Memorial Sloan Kettering Cancer Center, discusses the emergence of the androgen receptor splice variant-7 (AR-V7) biomarker in the treatment of patients with prostate cancer.

AR-V7 has been previously studied in circulating tumor cells in men with castration-resistant prostate cancer to identify primary resistance to enzalutamide (Xtandi) and abiraterone acetate (Zytiga) therapy.

AR-V7 is currently being looked at as a biomarker to find an appropriate patient population, wherein physicians then may be able to use combinations of other drugs to overcome resistance to targeted therapy.

According to Rathkopf, biomarkers like this are the key to understanding and mitigating resistance in prostate cancer.

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Dr. Rathkopf on AR-V7 Biomarker in Prostate Cancer

Dana E. Rathkopf, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses agents being explored as treatments for patients with prostate cancer, including apalutamide and PARP inhibitors.

Apalutamide, a non-steroidal antiandrogen agent, is different from abiraterone acetate (Zytiga) and enzalutamide (Xtandi), as it has not yet been approved for regular use. The agent has shown efficacy in phase I and II studies, and there are several ongoing phase III registration studies looking at the drug. However, since it is not FDA approved, it is not yet available for everyday patients who are not on clinical trials. The pressing question Rathkopf asks is, "Can this drug get approved in this space to make it available for patients in need?"

There is also ongoing work being done regarding PARP inhibition in prostate cancer. One study that was recently completed by Maha Hussain, MD explored the combination of a PARP inhibitor plus abiraterone. Then, another ongoing study is investigating abiraterone plus a PARP inhibitor. Additionally, researchers will be stratifying results based on DNA-repair deficits, Rathkopf says. Results from these trials are highly anticipated amongst the community, she adds.

Dr. Rathkopf on Investigative Agents in Prostate Cancer

Dana E. Rathkopf, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses mitigating androgen receptor (AR)-resistance in patients with prostate cancer.

AR is a very important target for prostate cancer, Rathkopf explains. Additonally, AR-targeted agents have only been available for patients with prostate cancer for about 5 years. Researchers in the field are now trying to catch up and determine which patients are best candidates to receive AR-targeted therapy, as well as working to identify what the mechanisms of resistance are and if combinations with chemotherapy, immunotherapy, or DNA mismatch-repair agents will improve outcomes.

There are phase III studies ongoing in this space that have completed accrual. One is an ALLIANCE study exploring the AR-targeted agent enzalutamide (Xtandi) versus enzalutamide plus abiraterone acetate (Zytiga; NCT01949337). There is also another phase III that is comparing abiraterone with or without apalutamide, which is a second-generation AR-directed agent. Both studies are highly anticipated in the field, Rathkopf concludes.

Dana E. Rathkopf, MD

Articles

Dr. Rathkopf on AR-V7 Biomarker in Prostate Cancer

Dr. Rathkopf on Investigative Agents in Prostate Cancer

Dr. Rathkopf on Mitigating AR-Resistance in Prostate Cancer