Clinical Implications of New Data on Apalutamide + ADT in Castrate-Sensitive Prostate Cancer

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Clinical Implications of New Data on Apalutamide + ADT in Castrate-Sensitive Prostate Cancer

Interview with Neeraj Agarwal MD Interview by Sumanta Kumar Pal MD

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Clinical Implications of New Data on Apalutamide ADT in Castrate-Sensitive Prostate Cancer

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Dr. Sumanta Pal:

Welcome to Practice Update. My name is Monty Pal and I'm a GU medical oncologist at the City of Hope Comprehensive Cancer Center. I always enjoy doing these interviews for Practice Update, but I'm particularly delighted to have my good friend and colleague, Dr. Neeraj Agarwal, here, who directs the genitourinary program at the Huntsman Cancer Institute in Salt Lake City, Utah. Neeraj, welcome.

Dr. Neeraj Agarwal:

It's always a pleasure, Monty.

Dr. Sumanta Pal:

Thanks, and I've got to tell you, I am so excited for you at this meeting. New England Journal publication yesterday, you know, related to the TITAN trial. Can you tell us about TITAN?

Dr. Neeraj Agarwal:

Yes, and we are very excited about the results. TITAN was a phase III registration trial with more than 1 thousand patients with newly diagnosed metastatic hormone-sensitive or castration-sensitive prostate cancer who randomized a standard of care therapy with testosterone separation and/or testosterone separation or androgen deprivation therapy with apalutamide. As we know from the previous studies of apalutamide in nonmetastatic castration-sensitive prostate cancer, this is a very important direct androgen receptor inhibitor, a new class of drug, which also represents enzalutamide, for example.

So, these two drugs belong to androgen receptor potent AR inhibitor and for the first time, this drug was tested in this metastatic castration-sensitive prostate cancer setting and what we see was really remarkable. This is for the first time, in this class of agent, which is apalutamide, increased both overall survival and radiographic progression-free survival at the first interim analysis so which was the most striking thing, I think, in my view, is how early we saw the results, improving both radiographic progression-free survival and overall survival and please note that this study allowed patients to have received docetaxel chemotherapy. This study allowed patients with low-volume and high-volume metastatic disease, so really this study was for all patients who have metastatic prostate cancer which is newly diagnosed.

Dr. Sumanta Pal:

It's really interesting and I congratulate you on the results. It's becoming a crowded landscape, isn't it? So, you've got abiraterone potentially, you have enzalutamide, apalutamide. For our viewership, now help them understand the place of apalutamide in this context.

Dr. Neeraj Agarwal:

That's a great question. So, for me, decision making is very simple. I have hardly come across a patient, and I'm sure this is your experience also, who is enthusiastic about receiving chemotherapy with all the short-term and long-term side effects of chemotherapy. So, in my view, docetaxel is obviously not a contender here because there's no enthusiasm for continuing chemotherapy in our patients anywhere, regardless of the setting. So, when you have such a...we have such strong results coming from an oral pill, the decision making is pretty simple.

Another competition is abiraterone with prednisone, a steroid. Again, patients have concerns about being on steroids for three years. The median progression-free survival in this setting is approximately three years, or at least a year 00:03:25 and to be on steroids, corticosteroids, for years is a concern, given the long-term side effects of these drugs. So, I think abiraterone with prednisone is clearly not a match for an agent, which is an oral pill, but doesn't require corticosteroids and is highly well-tolerated. It was very satisfying to see that level of fatigue was not significant and we will present quality of life data in upcoming meetings and hopefully, we'll be able to allay any concerns about any of the side effects like fatigue, which are really associated or at least seem to be associated with this class of drug, doesn't seem to be a concern.

Dr. Sumanta Pal:

Yeah, but it seems like a slam dunk. Not chemotherapy, no steroids necessary in this context, and less fatigue than you see with enzalutamide. It seems like a definitely preferred regiment frontline. Is that safe to say?

Dr. Neeraj Agarwal:

Yeah. So, I would like to make it very clear that this drug has not been compared with enzalutamide in a, you know, in a randomized setting. So, without comparing with enzalutamide, I can tell you that as far as decision making regarding selection of chemotherapy or abiraterone is concerned, apalutamide clearly has an edge and given how well-tolerated the drug has been in the TITAN study, I don't have any doubt that this is one of my preferred drugs in this setting moving forward.

Dr. Sumanta Pal:

That's fantastic. Very good. Very good and just for the folks who get some experience with apalutamide, see their patients progress and develop further castration-resistant disease, what are you using there? Are you starting to get some experience for treatment beyond these first-line therapies?

Dr. Neeraj Agarwal:

That's a huge challenge for us now. So, this is a great news that these patients are living so much longer, years longer than what we used to see. So, when my patients living much longer, obviously, this is very satisfying, very gratifying, but now next challenge comes is when you're living longer, we are allowing more time for tumors to evolve, to acquire more mutations, more newer capabilities and I think that's a next challenge. How to treat these patients who are developing castration-resistant prostate cancer having received or experienced upfront, intensified regimens in the past.

Dr. Sumanta Pal:

Well, I smell another New England Journal paper for you, Dr. Agarwal. Well, congratulations on your fantastic paper and I wish you continued success and thank you so much for joining us today.

Dr. Neeraj Agarwal:

Thank you very much for having me.