ASCO GU: A Decade of Advances in Prostate Cancer With More to Come

Charles J. Ryan, MD

The 2014 ASCO Genitourinary Cancers Symposium was held January 30 to February 1 in San Francisco. Today we are joined by Charles J. Ryan, MD, professor of clinical medicine and urology at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, and leader of the Genitourinary Medical Oncology Program, who will discuss highlights from this year's meeting.

-Interviewed by Leah Lawrence

Cancer Network: Dr. Ryan, this year was the 10th anniversary of the Genitourinary Cancers Symposium. Can you discuss some of the major advances in the field in the last decade?

Dr. Ryan: The last decade has been a decade of tremendous advances in the management of advanced prostate cancer as well as refinement and advances in the management of localized prostate cancer and even the assessment of prostate risk in terms of who should receive treatment. More to the point of the most recent advances, we have seen a number of new agents and new therapies of multiple different classes that have gained regulatory approval and, more importantly, widespread use around the world for patients with advanced prostate cancer. The survival of these patients is increasing quite significantly as well.

It is interesting to look back 10 years ago. It was 2004 when the Tax 327 chemotherapy study was published and when docetaxel received its FDA approval. At that point, we were looking at patients with a median survival of about 19 months entering into clinical trials. Now, more or less, we are seeing that similar patients are surviving 30 months, 35 months. We are seeing clinical trials now where the survival is getting out into that range. Overall, a number of new options are available and our sense is that the survival of patients is increasing quite a bit as well as the quality of life of these patients.

Cancer Network: Several exciting studies came out of this year's meeting. Can you briefly discuss?

Dr. Ryan: The top study that was presented this year was that which was presented by Dr. Tomasz Beer from Oregon Health Sciences University. He presented preliminary results of a phase III clinical trial in men with metastatic castration-resistant prostate cancer. This is a study with enzalutamide, which is already FDA approved but approved in patients who have docetaxel-resistant disease. His trial, which enrolled about 1,700 patients, demonstrated a very significant improvement in overall survival as well as progression-free survival for patients with metastatic castration-resistant disease. Enzalutamide is a very important new therapy. This trial, by demonstrating, for example, that the therapy decreases the risk of radiographic progression by as much as 80% over placebo, will most likely move this therapy into earlier patients and allow more of them to receive the benefits of this important drug.

That is the top abstract that was presented and that was a late-breaking abstract. In addition, there have been a couple of other important observations in updates from other trials.

Dr. Sophie FossÃ¥ from Norway presented a 10- to 15-year update of prostate cancer specific survival in patients who received long-term hormonal therapy for prostate cancer. This was an important study from the standpoint of that it was patients that received an anti-androgen alone or had received androgen ablation and an anti-androgen radiation. Essentially what she showed was these results continued to favor the use of radiation therapy and lifelong anti-androgens. Again, this builds on the concept of long-term hormonal therapy being beneficial for patients. This is an important study partly because it’s 15-year data, but it could be criticized because the treatments that are used are not necessarily those that are used today. Nevertheless, it is important data supporting the concept of radiation and hormonal therapy being used in combination.

Cancer Network: Of these trials, are there any that you feel will have an immediate effect on clinical practice?

The enzalutamide trial will affect our clinical practice. I think it is a fair assumption that this will be favorably received by the FDA here in the United States and a fair assumption that regulatory approval may change and expand to include these pre-chemotherapy patients.

This will bring a third agent into this pre-chemotherapy space, abiraterone and sipuleucel-T being the other two. I think this will open up therapeutic options for a lot of patients. It may create a little bit of confusion for some clinicians in so far as there will now be many options, many choices, and we don’t have any comparative data, for example, comparing enzalutamide to abiraterone for the practicing oncologist or urologist to make a data-driven decision.

Cancer Network: Finally, the last decade has brought major advances in the treatment of genitourinary cancers. What do you feel will be the major advances in the next few years?

Dr. Ryan: That is a great question. As I look to the next decade, I look to really a couple of things happening. One is we are clearly in a time of great advancement in our ability to interrogate tumors and to find drugable targets in these tumors. There are a number of major efforts underway to characterize the biology of progressing prostate cancer. What this means is down the road we may not have to do these 1,700-patient or 1,000-patient randomized phase III trials. We might be able to select patients based on the presence of a particular marker or of a particular target or a particular biomarker, and treat a smaller number of patients with that. This even gets down to terms that you hear like “n of 1 trials” meaning one person entering a clinical trial, which means under certain circumstances there are very interesting results coming out of one patient who has that dramatic response to a particular drug because they harbor a mutation that makes them sensitive to that particular agent. That is what I think is going to be a major effort in the coming years.

The second thing is what we are seeing is that all of these agents and drugs that are coming into late-stage disease are gradually moving their way into earlier disease. Even into patients with high-risk prostate cancer who have not even had surgery yet to remove the prostate. We may see that some of these newer agents get used upfront and, by extension, if there are better results, we may actually see that these agents are able to cure some individuals by eliminating disease before surgery is done. That would be tremendously exciting so that we might do more treatment for patients upfront and have fewer patients that experience castration-resistant prostate cancer and as a result, fewer patients who die of the disease.

Cancer Network: Thank you again for taking the time to speak with us today.

Dr. Ryan: My pleasure.