Managment of advanced prostate cancer

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Published: 26 Jul 2017
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Prof Daniel Petrylak - Yale Cancer Center, New Haven, USA

Prof Petrylak talks with ecancer at NOSCM 2017 about the management and treatment of advanced prostate cancer and new drug approvals for prostate cancer. He goes on to discuss new FDA drug approvals and the benefit on survival rates for patients with prostate cancer. He continues by talking about the side effects and secondary effects of the new drugs outlined.

Prof Petrylak last spoke to ecancer at the Best of ASCO 2017 meeting in Miami about the use of abiraterone for prostate cancer.

I’m going to be talking about the management of advanced prostate cancer today. Prostate cancer has evolved over the last 10-15 years as far as the treatments are concerned. In 2004 we only had one treatment which was demonstrated to improve survival and that was docetaxel. Since 2010 we’ve had five approvals by the FDA for various different drugs in various different classes for castrate resistant prostate cancer. These include other chemotherapeutic agents such as cabazitaxel, hormonal agents such as abiraterone and enzalutamide, isotopes such as radium-223 and immune agents such as Provenge. The real question that comes forth from the clinician is how do we best sequence these agents and how do we maximise their therapeutic efficacy and that’s really not known at this particular point.

But what we’re seeing now are several different trends. Firstly, moving some of these treatments up earlier in the course of metastatic disease, before patients become castration resistant, seems to give a better outcome as far as survival is concerned. That’s seen with both abiraterone recently from the STAMPEDE trial as well as the LATITUDE trial as well as docetaxel from the STAMPEDE trial as well as the CHAARTED trial.

We also are beginning to identify different molecular targets that we can move forward with or help to stratify our patients with prostate cancer. These include BRCA and DNA repair mutations. We know that drugs such as PARP inhibitors do have effects in these particular patients who harbour these mutations. Additionally we can find markers of resistance to hormone therapy such as ARV7. So it’s becoming much more complicated and requires a much more sophisticated approach and drug selection for our patients with metastatic disease.

Do these drug combinations increase survival statistics?

Absolutely. As I said, in 2004 docetaxel was approved by the FDA and that was the first agent that demonstrated a survival benefit, albeit it was modest in metastatic disease, about three months. If we look at all of the other agents such as abiraterone, enzalutamide, Provenge, radium, cabazitaxel, although that’s a second line agent, we see that the survivals range between 3-5 months, or the improvement in survivals range between 3-5 months. So we’re seeing modest survival benefits when we move some of these drugs earlier, such as docetaxel or abiraterone. We’re seeing a much greater impact on the patients, a hazard ratio of about 0.75, which is about a 25% reduction in the risk of death in a high risk patient with metastatic prostate cancer. If they get docetaxel upfront they can get about a ten month improvement in their median survival. So that’s showing a bigger effect when you’re giving it earlier.

Are there many secondary effects from these new drugs?

We’re learning how to manage the side effects better than we did before. Certainly with the hormonal agents fatigue does seem to be an issue, the same thing with chemotherapy. We’re better managing this by looking at different drug schedules and trying to encourage the patient to exercise and do other things that may make them more energetic. Neutropenia, now we’re using growth factors to support that with patients who are receiving chemotherapy. So we have better secondary treatments to help us improve the outcome in these patients, better toxicity and hopefully more drug administered, this potentially could lead to a better outcome.