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Expert Discusses Evolving Role of Chemotherapy in Hormone-Sensitive Prostate Cancer

Published: Wednesday, Oct 26, 2016

Tanya Dorff, MD

Tanya Dorff, MD

Several recent trials have supported the use of chemotherapy in the frontline setting for patients with hormone-sensitive metastatic prostate cancer.

For example, in the phase III CHAARTED trial, the median overall survival was 57.6 months with the addition of docetaxel to androgen-deprivation therapy (ADT) versus 44 months with ADT alone (HR, 0.61; 95% CI, 0.47-0.80; P <.001) in patients with metastatic, hormone-sensitive prostate cancer.

At the 2016 OncLive State of the Science Summit on GU Cancer, Tanya Dorff, MD, an assistant professor of Clinical Medicine, Keck School of Medicine, University of Southern California, discussed developments in the upfront treatment of hormone-sensitive metastatic prostate cancer.

In an interview with OncLive, Dorff highlighted the key points of her presentation, including the integration of chemotherapy into the frontline setting and the development of biomarkers to personalize treatment in this population.

OncLive: Can you provide an overview of your lecture at this State of the Science Summit?

Dorff: I discussed the role of chemotherapy in hormone-sensitive prostate cancer. This is largely based on the very exciting CHAARTED trial results that were presented at the 2014 ASCO Annual Meeting by Dr. Chris Sweeney. However, there are 2 other large randomized studies that have shed some light on this. We looked at those 3 trials and then some practical tips as to how to select patients for whom this is the right approach.

What are the big takeaways from those trials?

The big takeaway is that we always knew chemotherapy worked for prostate cancer, but we used it at the time of castration resistance—when hormone therapy was starting to fail. These trials show that using it early for a newly diagnosed patient with metastatic prostate cancer who is just starting out on hormone therapy actually creates an even bigger impact. However, there are some caveats. Chemotherapy has its toxicities and there may be certain groups of patients, particularly high-volume patients, for whom the benefit is much greater and worth any risk that comes with it.

The first study is CHAARTED, which was the intergroup trial of ADT alone or with 6 doses of docetaxel upfront. The second trial is the GETUG 14 study, which were similarly patients with metastatic prostate cancer receiving upfront hormone therapy alone or 9 cycles of docetaxel. The third study is STAMPEDE, which is a very large study—about 2000 patients and 4 arms— and was much more complicated. The standard of care was ADT with or without radiation therapy, and then 3 non-standard arms: one with zoledronic acid, one with docetaxel, and one with both. This is also a little bit of a different study because it wasn’t purely a metastatic population. There were some high-risk or locally advanced type patients in there.

What are some factors you consider to determine what therapy is best for patients?

The high-volume versus low-volume disease is a good stratifier. It is pretty clear that someone with just a few pelvic lymph nodes and just 1 or 2 bone metastases doesn’t stand to gain as much from intensifying therapy early on. Then, you have to look at your patient’s age, frailty, and comorbidity because there is significant toxicity that can occur with docetaxel. You do get febrile neutropenia. There were some deaths on some of these trials in the chemotherapy arms.

Typically, I talk to patients about the risks. I’ll assess their robustness. Most oncologists have a good eye for someone who is going to get through chemotherapy well versus not. There are also some formal tools that can be applied, especially in a geriatric population, which is a large part of our prostate cancer population. There are geriatric comprehensive assessments that might be able to help give a more objective or quantifiable reason why someone may or may not be a good candidate for chemotherapy. However, most of us are using a lot of our gut instinct on that.

For patients with hormone-sensitive prostate cancer, is there 1 approach that is best for most patients, or does it vary from individual to individual?

These studies that tested docetaxel upfront added to hormone therapy represent a selected population. We know that clinical trials don’t always reflect everyone who presents to an oncologist’s office. That being said, they did have broad inclusion criteria and the trials are broadly applicable. However, it doesn’t mean that every single patient needs docetaxel upfront.

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