Video: Olaparib and Keytruda For Advanced Prostate Cancer | | Learn About Clinical Trials

Learn About Clinical Trials | Transcription

Hi, I'm Dr. Scholz. Let's talk about clinical trials for prostate cancer patients.

Clinical trials are an important part of expanding our armamentarium of treatments for prostate cancer. Research is what leads to new treatments and the thinking that goes into designing a clinical trial usually is looking to find a fix for an unmet need. 

In the clinical trial we're covering today, the unmet need is men with advanced prostate cancer who've already been treated with a second-generation hormone medication such as Xtandi or Zytiga and have also had Taxotere, the common type of chemo used for advanced prostate cancer. In the situation where these treatments have been utilized already and have stopped working, what's the next step? 

Well, there's a few options, but options are starting to get narrower. Probably, one of the most common next steps is if a man has been previously one second-generation hormonal agent (such as Zytiga), they're switched over to another second-generational agent such at Xtandi or vice versa. If someone's already on Xtandi and the disease is progressing, people can be switched over to the Zytiga to try the other agent. This will be helpful in some people, but the consistent results aren't that good and even when men do get responses, they tend to be brief. 

So, Merck pharmaceuticals is evaluating two of their medicines that have shown activity in prostate cancer patients. Both medicines are FDA-approved for other types of cancers. Olaparib (or Lynparza) is approved to treat ovarian cancer. Keytruda, an immune medicine, is approved to treat a variety of things including lung cancer, bladder cancer, and melanoma. 

So, in this trial, men are either going to be allocated to switching over to another second-generation agent on one hand or they'll be randomly allocated to get a combination of Lynparza and Keytruda, and then they'll compare how quickly the disease progresses with these two different approaches. They're, of course, trying to demonstrate that there'll be a delay in the time to new metastases and longer survival. 

So, just a little bit of background about Lynparza and Keytruda. Both of the medicines have been evaluated in Phase-II trials in prostate cancer. That means, just looking for activity, and there is activity. The Lynparza (or olaparib) is particularly active in men that have a certain mutation called BRCA, but this mutation is not required for this clinical trial. Lynparza does have activity in men that are not burdened with the BRCA mutation. So, the arm that gets treatment will be both medicines in combination—Lynparza plus Keytruda. 

So, what are the medicines like? Well, Lynparza I think of as sort of like a chemotherapy, but without the hair loss. Chemotherapy can cause fatigue, it can cause low blood counts. Lynparza is a pill. You take an oral medication twice-a-day. You have to be monitored just like you would be if you were getting chemotherapy. Keytruda is an immune medicine and immune medicines have become very popular for a variety of cancers. There is a type of immune medicine for prostate cancer called Provenge, but Keytruda works by a different mechanism. It's described as taking the brakes off the immune system in general. It's an infusion every three weeks. Generally well tolerated. About 20% of men will have some notable side effects due to the overactivity of the immune system. So you can get asthma or diarrhea or rashes, those sorts of things.

So, both Lynparza and Keytruda are fairly potent anti-cancer agents and there certainly will be an issue with side effects, but the men that are facing progressive disease after a second-generation agent has stopped working and after chemotherapy has stopped working really need some answers and I think both these medicines in combination offer a real genuine hope of controlling this type of aggressive prostate cancer. So, for further information, we'll provide a phone number and a website for people. I believe there are over 100 sites that are doing this clinical trial. It has been open since May and they are actively recruiting.