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Expert Discusses Novel Therapies, Biomarkers in mCRPC

Gina Columbus @ginacolumbusonc
Published: Wednesday, Aug 24, 2016

Jingsong Zhang, MD, PhD

Jingsong Zhang, MD, PhD

With a half-dozen newly approved therapeutics, the treatment options for metastatic castration-resistant prostate cancer (mCRPC) have greatly expanded since 2010. Researchers are now looking to refine use of these agents and expand into new therapeutic areas.

Jingsong Zhang, MD, PhD, discussed these advancements in his lecture during the 2016 OncLive State of the Science Summit on Genitourinary Cancers. Zhang covered sequencing, the pathophysiology of the androgen receptor, the expanding array of hormonal approaches, strategic timing for cytotoxic therapy, and PARP inhibition and other appealing targets.

In an interview with OncLive during the meeting, Zhang, a medial oncologist at Moffitt Cancer Center, discussed the key takeaways from his talk and his vision for treating patients with mCRPC.

OncLive: Please provide an overview of how advanced prostate cancer has been an exciting field in recent years.

Zhang: Since 2010, there are 6 drugs approved for treating this disease where the cancer becomes late stage IV, and patients no longer respond to hormonal therapy, such as androgen-deprivation therapy (ADT), and things such as leuprolide acetate for depot suspension (Lupron). Five of [these agents] are based on an improvement of overall survival.

After that, the field is wondering how to sequence them, and perhaps, for some patients, we need to [look at combinations]. In the past 2 years, there have not really been any advancements in terms of how to sequence these treatments.

One important trial is the CHAARTED study, which was published last year for high-risk patients with high-volume disease. There is a [reason] to give upfront chemotherapy when patients first start ADT. That has been shown to be beneficial, in terms of improvement in survival.

Later on, in terms of the tumor markers, there is AR-V7—which shows a pretty good predictive marker in terms of response to newer androgen-deprivation agents such as abiraterone acetate (Zytiga) and enzalutamide (Xtandi).

There are phase III trials ongoing right now that are specifically targeting this patient population, but they have positive AR-V7 in their circulating tumor cells (CTCs). There are a lot of efforts to try to understand the underlying biology of this disease; that is really from the tremendous efforts of just doing next-generation sequencing of the prostate cancer. Many trials mandate biopsy for patients with metastatic disease. In the past, not many patients with metastatic prostate cancer got a biopsy. That’s kind of the hurdle to learn about this disease when they progress to late stage.

Therefore, a lot of sequencing works. We found biomarkers. We found out there is enrichment of DNA damage repair deficiency proteins, and that there are agents to explore such as PARP inhibitors. There is a phase III trial planned for patients with stage IV prostate cancer using the PARP inhibitor and conducting biomarker studies.

Those are the exciting things in the field of prostate cancer. It keeps evolving. First, we have new agents; then, we try to figure out how to sequence these agents. Perhaps for some patients, we need to combine these different agents. All of this is based on understanding the biology, and we are learning more about the biology of this disease when patients progress to late stage IV. It’s definitely a different disease compared with initial prostate cancer presentation.

You discussed the pathophysiology of the androgen receptor, as well as an expanding array of hormonal approaches. What were the main points of this portion of the lecture?

The key point is to bring up to date the AR-V7 and the qRT-PCR assay platform. It is not really 100% that, if patients are positive for AR-V7 on the qRT-PCR assay, they will have no response to treatment. What is more important is that the same AR-V7 prognostic predictive value is also confirmed with another platform.

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