DR LOVE: How do you approach a patient, Mario, who has symptomatic metastatic disease who is progressing on docetaxel? What’s your usual next move? And what do you do in the older patient who’s chemotherapy adverse or you’re adverse to giving them chemo?
DR EISENBERGER: If a patient has had a very good response to docetaxel and progressed around the time where we usually see the progression to docetaxel and if the patient is well in general — that is, no pain, performance status is good, motivated, was helped clinically by the initial treatment with docetaxel — I would offer cabazitaxel. I think that’s the only cytotoxic chemotherapy that, in that setting, is shown to prolong survival.
Of course, another option would be to administer docetaxel. I would offer docetaxel for those patients who responded to docetaxel and, as everybody else here, would give them a break somewhere between the fifth and the seventh cycle. And if they didn’t progress, certainly that’s an option, particularly since if the tolerance was very good. That’s certainly another option.
But now that we have the abiraterones, the enzalutamides, it’s tempting to offer these compounds to those that haven’t had it, to offer them before we move to the next chemotherapy setting. I think that there’s still major room for clinical trials in patients who fail first-line chemotherapy.
DR LOVE: Susan, how do you approach a patient who is progressing on first-line chemo, symptomatic?
DR SLOVIN: I will usually go for an investigational trial.
DR LOVE: And if no trial is available?
DR SLOVIN: Then I will go to cabazi as my choice.
DR DREICER: I mean, now the answer for me would be abi, almost certainly. Because I can give abi now. I think enzalutamide would be an equally appropriate choice. But that’s not relevant. You’re going to come back to the same thing in 2 years, because in 2 years from now, everybody’s going to get these, who’s going to get enzalutamide and abi up front, that are going to get docetaxel later, and then the issues about postdocetaxel management are going to come back. But radium-223 chloride is going to be around, so it’s going to be the same discussion now, but a little bit further down the stream because their secondary hormonal therapy is going to be already used.
DR OH: You didn’t ask this question, but I’ve been asked this question: Is chemotherapy going away? And I think the answer is no. And I think the answer is no because there’s clearly a subset of patients who get tremendous benefit from chemotherapy. This gets back to the question of whether we can predict those patients, because there’s clearly other patients who suffer from chemotherapy and don’t get much benefit. But I think that ultimately, the resistance pathways, for example, in the androgen pathway, eventually drive patients to be potentially very good candidates for chemotherapy, and I think that there will continue to be chemotherapy use in advanced prostate cancer.
DR SARTOR: I agree with William that I don’t think that the chemotherapy is going away. One thing I did want to mention about these trials that I think is important: In each of PROSELICA and FIRSTANA trials, they’re using a contemporary regimen as the comparative group. And we’re using cabazitaxel or we’re using docetaxel at appropriate doses. One of the things that we have to be aware of when it comes to the original docetaxel, the standard of care, which was very appropriate at that time, was mitoxantrone.
But the things I’d like to applaud about this particular set of trials is they’re using contemporary standards as a comparator arm. And I think that’s where we need to go, because we’ve got a whole bunch of trials right now still using placebo or this or that. And that’s not where the field is.
DR LOVE: So again, for practical purposes, though, you’ve got a patient who gets docetaxel first line with symptomatic disease, does not respond.
DR SARTOR: I think that the enzalutamide, abiraterone ought to be tried. And at the same time, I think you’re still going to be able to meet the cabazitaxel down the line or a clinical trial, as Susan said, which is always an appropriate choice.
DR PETRYLAK: My question is, as you go on these subsequent treatments, should you continue abi? Because unlike an antiandrogen, where you have an antiandrogen withdrawal effect, whether you are stopping abi at that particular point, are you putting fuel on the fire by allowing a release of testosterone within the cells and then repeat synthesis? So I think that’s a really important question. Is that going to worsen or improve your response to the treatments?
DR LOVE: What’s your answer right now?
DR PETRYLAK: I don't know. I honestly don’t know.
DR LOVE: What do you do?
DR PETRYLAK: I stop it, because that’s what we traditionally have done. But we don’t have a good answer from the clinical trials.
DR LOVE: So Matt, again, the patient doesn’t have a good response to docetaxel. What’s your next move?
DR SMITH: Very difficult to roll that patient over onto a second-line chemotherapy, depending on how many cycles he’s had. So given the availability, abiraterone acetate and enzalutamide are welcome, so you give a chance to use a better-tolerated treatment before going on to cabazitaxel.
DR LOVE: Any thoughts about Dan’s issue, a question about continuing abi?
DR SMITH: It’s a great question. There’s a clinical trial. The Phase III clinical trials were designed to stop at clinical progression. So that’s what we know, and not more. It certainly is an open question as to whether continuing treatment would be preferable. There are, of course, major concerns about potential additive toxicities in combination with other therapies. There’s tremendous cost involved. Payers will have an opinion about this for sure. And I don’t think we can, at the present time, recommend doing so.
DR BEER: So, I just want to point out that the PREVAIL trial, which is a prechemo study of enzalutamide, does actually allow continuation of enzalutamide past progression. It’s not going to be a randomized comparison of progression versus non, so it’s not going to give us a definitive answer. But it’ll give us some preliminary data on this concept. There’s clearly some economic toxicity to doing that.