Expert perspectives on the PROSELICA trial, which helped inform optimal dosing strategies with cabazitaxel in metastatic castration-resistant prostate cancer.
Tanya Dorff, MD: Let’s talk about dosing because I think that’s an important issue when we’re trying to balance risk and benefit. Maybe you can talk to us about the PROSELICA trial [NCT01308580].
Elisabeth Heath, MD, FACP: I liked having data to point to, as opposed to winging it. We do our fair share of that. PROSELICA is a really important study because it did look at the dose between 25 milligrams per meter squared [mg/m2] vs 20 mg/m2. In my practice, I use 20 mg/m2, and then sort of work my way down if there are other concerns, like the blood counts maybe are not as robust. In this case, the study was…a noninferiority design. There were a lot of men on this trial. It was 1200 patients who really contributed to this 1:1 randomization. And they took patients who had an ECOG score of 2. This is our group where, when you’re third line and starting to worry a little bit that maybe they’re not as robust as you want them. But like you said, when you have uncontrolled cancer, you don’t feel well. I do say the same thing you do: that when you do have controlled cancer, you might feel well, and that might mean feeling better on chemotherapy vs off. I think that’s a different way than we think about things. You and I like overall survival [OS], and I think that’s pretty similar. I think the OS on the 20-mg/m2 arm was 13.4 months. And then it was 14.5. The hazard ratio was basically 1. So, you look at that and say, “Well, I think 20 is very reasonable.” In my practice, patients tolerated it without much concern. I still use growth factors. We’re not going to play the hero there. But I think it’s good enough for me to feel confident to use this dose. I don't know [whether] you do that as well, in your practice. Or are you sticking to the 25?
Tanya Dorff, MD: No, I did adopt the 20 mg/m2 after seeing those data. But then what threw a little bit of a wrench in that is the CARD trial [NCT02485691]. The CARD trial provides some fairly compelling data, but they did go back up to the 25-mg/m2 dose. So, there are some scenarios where I might start at 20 and try to go up to 25. Although you’re right, PROSELICA is really quite compelling. The dosing at 20 is effective.
Elisabeth Heath, MD, FACP: And there were these post hoc analyses. Sometimes we’re not too enamored with post hoc, because you’re like, “Well, are you just looking at another data set to come up with things?” But I do think that a couple of the studies that were looked at for post hoc were important. Because I want to know, and you want to know, that what we are doing is actually improving patients’ quality of life, whether it’s pain or something else. And when you’re asking that question in this analysis, I think that gives us some comfort that isn’t just my view on this or your view. But there really is. So, one of the studies—I think this was published last year—was actually to look at the different parameters. And these are the things that I look at, and I’m sure you do as well. If you progress, how do you define that? It’s the hand wringing in clinic, like, “Did this stop working because your PSA [prostate-specific antigen] worsened?” Is it just their imaging is worse, but the PSA is maybe not? Or is it just, “I’ve got a lot of pain, and this is going nowhere?” It’s hard to strategize those 3 moving parts. Because sometimes the pain is really gone, and they feel terrific but all the other parameters look like everything’s going sideways. And then you’re looking at the patient, and you’re like, “You look great, and you’re gaining weight, and you’re not on that much pain medication.” I think, looking at this, it showed that the thing we’re fussing about—which I think is right—is that pain progression is just associated with a poor prognosis. When you’re looking at trying to improve that, it’s important to recognize, from a patient level, that’s important. On a post hoc, the median OS in the pain group was 12 months, compared [with] just the PSA-only progression, which I think was at 18 months, or 18.4 months. And then the imaging progression was at 16.8 months. The take-home for me there is you’ve got to watch the pain story because it may be that they’re just getting steroids along with it. But they were also, with docetaxel. They were also, probably, on abiraterone. So, I’m not sure [whether] that’s the whole story. I think here, the chemotherapy has a job to do, and has done that job. And it’s something to not pooh-pooh. Then the other study that also came out last year was to look at PROSELICA, but also FIRSTANA [NCT01308567], which is cabazitaxel right up front and formally looked at the quality of life. Here, it’s the same thing; Response, PSA, pain, and how are we doing? And for those who have had a pain response, the quality of life happened; in terms of when it happened, it happened early, and it was maintained. And so, I think we can’t ignore that. I know we tend to get excited about PFS [progression-free survival] and OS. And, “Look at this marker, and look here.” But I think these are 2 post hoc analyses that really looked at it from a patient benefit.I don’t know [whether] you see that in your practice, in terms of improvement of pain, and just them feeling overall better controlled.
Tanya Dorff, MD: Absolutely. I sometimes describe it to my patients as a Lazarus response. People can go from being so limited by pain. And weight loss is another one that you pointed out, and that really worries me. That’s a sign when I know someone’s not doing well. And when you see that turnaround, and they’re gaining weight, and they’re able to get out of the house and do more, it’s really gratifying. I do always talk about that triad. “We [must] look at your PSA and your scans, but we also [must] look at you. How are you doing?”
Elisabeth Heath, MD, FACP: Right? Because I think, if they don’t see that improvement, we can say all we want. And say, “Well, I’ve got this as a next step. I’ve got that as a next step.” And they’re going to be like, “Mm-hmm, OK. I feel lousy, doctor, so I don't know what you’re doing, but whatever you’re fantasizing about over here isn’t really helping.”
Transcript edited for clarity.