The TITAN Study: Secondary End Points


Neeraj Agarwal, MD, and Simon Chowdhury, MD, comment on the secondary end points from the final analysis of the TITAN trial.

Simon Chowdhury, MD: We’ll go to the next slide, which has the secondary end points. The graphs here are very powerful. For me, the ones that are most powerful are B and C. I’ll see whether Neeraj agrees with me. B is the time to PSA [prostate-specific antigen] progression. PSA is so important in the clinic because when patients come in, they’re asking about their PSA. Patients often refer to PSA as the promoter of stress and anxiety. You can see here that time to PSA progression with ADT [androgen deprivation therapy] alone is only 12.9 months. Most of figure D, castration resistance, is driven by PSA. Those 2, B and D, are very similar.

This is a double-blinded study, with big recruitments to this study. Patients didn’t know the benefit of PSA control and the psychological impact it has. When a patient comes in to see Professor Agarwal, they’re anxious. One of the first things he’ll do is sit down and say, “The PSA is well-controlled,” and the patient will relax. You see them physically relax in front of you. They’ll say, “I had that bit of ache in my shoulder, probably from playing tennis. There’s nothing really there.” I’ve had patients say to me that the pain goes away as soon as you tell them the result.

The other one is C, which is progression-free survival 2 [PFS2]. This is about the second treatment. We have PFS1, which we know was significantly positive from the New England Journal of Medicine paper. Then it’s looking at what happens in the second treatment. This is all about what Neeraj was touching on earlier. Can you catch up? For a lot of people, ADT alone—we’ll talk about that a little in the discussion—still predominates in the treatment of men with metastatic castration-sensitive prostate cancer. That’s something Neeraj and I are trying to push back on, which is complicated.

Basically, this is saying that despite coming in with active second therapies—many crossed over to apalutamide, the same active drug that’s benefiting upfront treatment—those men never catch up. It’s a consistent story of PSA progression, PFS1 progression, PFS2 progression, and overall survival. There’s a consistency in the narrative, in the story. Do you have any other thoughts on this, Neeraj? You’ve been very involved in the PFS2. As an intuitive and empathetic doctor, PSA is something I’m sure your patients worry about as well.

Neeraj Agarwal, MD: Absolutely. PSA remains very important for all of us treating patients with prostate cancer, whether localized or metastatic. If I see the PSA decline, I know the drug is active. We can’t underestimate the value of PSA in the clinic. When I see these various end points that are being depicted by this slide—time to cytotoxic chemotherapy use, time to PSA progression, time to second progression, and time to castration resistance—these are very meaningful points that we discuss with our patients. If you ask me what the most meaningful end point after PSA progression is, it’s time to chemotherapy. In my career, I haven’t come across a patient in my clinic who’s excited about receiving chemotherapy. The fact that we’re seeing a significant delay in use of chemotherapy is also a very meaningful point. In my view, Simon, I show these pictures in front of us to my patients in the clinic. These are very reassuring data that emphasize the value of early intensification.

Simon Chowdhury, MD: As you said in a very eloquent way with the last slide, it’s consistency of the message, the story, and what we’re able to tell patients. It’s very reassuring in the clinic with patients.

The next slide is about quality of life. I’m going to pass it over to Neeraj for this because he has also published extensively in this area. He’s a great driver of quality of life and something that myself and other people learn from. But you also published in The Lancet Oncology on this, Neeraj. You’re the first author on that paper. There’s no one better to talk us through this slide, if you’re OK with that.

Neeraj Agarwal, MD: Absolutely. Quality of life is very dear to all of our patients and us as providers. Anytime we discuss any treatment with our patients, the No. 1 concern in my patient’s mind is how it’s going to affect their quality of life. Especially when we look at quality of life as reported by the patients—PROs [patient-reported outcomes]—without interference by the medical team, our provider team, that carries a lot of meaning for our patients.

This slide is showing the effect of apalutamide or early intensification with a deeper androgen blockade on the quality of life of our patients who were enrolled on the TITAN study. This is being measured by a standardized scale known as FACT-P [Functional Assessment of Cancer Therapy-Prostate]. It’s a validated tool that was used to assess the deterioration or measure quality of life in this trial. It’s very clear based on this slide that there was no deterioration of quality of life as reported by the patients when they were being treated with apalutamide on the TITAN trial. Another way to put this is that apalutamide improved survival without compromising quality of life. That’s my message, Simon.

Simon Chowdhury, MD: That’s very eloquent. We were chatting about this because Neeraj led many parts of the study, particularly this one. What do patients want? They want normality, and quality of life drives that. They don’t want to be patients. They want to be going to the cricket match or baseball game. They want to be going out with their family, grandchildren, and wives. They don’t want to be in the clinic. They don’t want to be labeled as men with prostate cancer. It’s always lovely to chat with Neeraj about his patients, because he understands that they’re people first and patients second. That’s an important message for all of us to remember.

Neeraj Agarwal, MD: In fact, because these are oral pills, which don’t require monitoring of laboratory tests or blood pressure, and they’re not on any concurrent other medications such as corticosteroids, I tell my patients, “Don’t think about us for next 3 months,” when I let them go. If you’re able to achieve that, it brings in true meaningfulness again to any treatment. That’s not only apalutamide. I’m making a general statement.

Simon Chowdhury, MD: You’re absolutely right. The other day, we were talking about this. We underestimate every blood test, scan, and clinic visit. Everything that isn’t normal, like coming to the hospital, having to find parking, and going in. I know patients love seeing Neeraj. He’s a charismatic, caring person. That isn’t the hard bit, but the other bits are. Having scans isn’t much fun. One of the things about active treatments is that you have to monitor them because there are subtleties and you can miss the nuance. But because of this and the excellent PSA control and because we know we can say, “You can go, come back in 3 months’ time,” they’ll walk out a couple of inches taller. That’s so important.

Transcript edited for clarity.

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