Cabazitaxel Use in Metastatic Prostate Cancer

Transcript:Raoul S. Concepcion, MD, FACS: I was at a meeting with a number of very well respected medical oncologists, and we were discussing, cabazitaxel or Jevtana, which as we know is approved only in patients who have already seen docetaxel chemotherapy. I was actually rather surprised that a number of medical oncologists, if it was approved in the pre-chemotherapy, pre-docetaxel space, they feel it might be a little bit better tolerated than traditional docetaxel.

Charles J. Ryan, MD: Absolutely.

Jorge A. Garcia, MD, FACP: No doubt. I think the biggest challenge that patients on docetaxel face is neuropathy, asthenia. And when you look, for instance, at cabazitaxel, outside the need for growth factor support because of their incidence of grade 3 and 4 neutropenia, it’s an agent that really doesn’t lead to neuropathy. Overall, I think cabazitaxel is a far better agent than docetaxel with regards to side effect profile. Now, if you look at, for instance, the TROPIC data with PSA and objective response, those numbers mathematically don’t look that different from what we saw with TAX 327. So we’ll see. There is an ongoing trial comparing head to head docetaxel and cabazitaxel. It is a superiority trial design that will define whether or not cabazitaxel actually will be superior to docetaxel in that CRPC setting.

Michael Fabrizio, MD, FACS: Haven’t they shown that in in vitro studies with the ATP pump mechanisms?

Jorge A. Garcia, MD, FACP: Yeah, absolutely.

Michael Fabrizio, MD, FACS: It’s less effective with cabazitaxel.

Jorge A. Garcia, MD, FACP: Correct.

Judd W. Moul, MD, FACS: Let’s say you have a young patient with M1 hormone-naive prostate cancer who gets referred, who starts docetaxel and has some neuropathy after cycle 2 or 3, can you switch to cabazitaxel to get those 6 cycles in? I know it’s off-label, but is that something that is being done?

Charles J. Ryan, MD: I wouldn’t say that I would be totally confident that there’s going to be less neuropathy with the cabazitaxel in that setting. And the other thing that’s interesting is, neuropathy is less of a problem in prostate cancer, I think, than it is in others. And that’s because we have so much experience with CRPC and because we’re giving the chemotherapy with prednisone. We haven’t talked about it, but giving chemotherapy in the castration sensitive setting is a different biology.

Raoul S. Concepcion, MD, FACS: Right, and I think people need to understand that CHAARTED and STAMPEDE discussed that hormone-naive patient. The discussion, as you appropriately said, Chuck, is that in the CRPC patient, that is a completely different patient. We’ve already altered the tumor microenvironment. But, again, correct me, there is a study currently that’s in the mCRPC space looking head to head at docetaxel versus cabazitaxel.

Jorge A. Garcia, MD, FACP: Yes. That was a postmarketing commitment the sponsors of cabazitaxel had with the FDA. In fact, there are 2 trials. One is the superiority trial against docetaxel and the other one is looking at a lower dose of cabazitaxel from the previous experience with the phase I and II data. I just want to go back to your point about the primary tumor and the importance of managing the primary tumor. In the management of prostate cancer patients, where you have advanced disease or not and haven’t addressed the primary, oftentimes these patients will go on to develop hematuria, progression in the bladder, and hydronephrosis. So I’m a pretty aggressive guy telling my younger patients, for that matter, that if you need ADT and chemotherapy, we’ll do it, but, at some given time, we’re going to have to address the primary.

Charles J. Ryan, MD: As I like to put it, patients who develop CRPC who have an intact primary tumor have a much more miserable time when they have complications there.

Judd W. Moul, MD, FACS: Let me just bring a point up for the urologists. I was at an international meeting for the SIU Congress that was just recently held. Laurence Klotz, who has done a lot of work in active surveillance and various things, presented a masterful talk looking at a meta-analysis suggesting that radical prostatectomy really has a benefit over radiotherapy in treating localized disease. Now, I know that’s going to be a politically incorrect statement to say as a surgeon, the radiation oncologist. But this was really compelling data looking at some very large series where— now, the radiation oncologist is going to say not randomized—but really robust, huge data sets.

Raoul S. Concepcion, MD, FACS: And Mike, I know you guys had published recently about the use of aggressive therapy. Again, I’ve been a big believer in that, because it’s the control of local disease. And when you miss that opportunity to take care of the primary, you wish you could go back and manage that. So this has been a great discussion. I think we’ve reviewed several important studies in prostate cancer and have discussed a lot in terms of treatment for castrate resistant prostate cancer as well as early localized in advanced disease. Before we end today’s discussion, I’d like to get some final thoughts from all the panelists. So Mike?

Michael Fabrizio, MD, FACS: Well, I think first, like we said earlier, we wouldn’t be having this conversation 8, 10 years ago. I think it’s exciting and we have a lot of options for our patients now. I think the key is to treat these patients earlier, recognize advanced disease earlier, and I think that is the take-home message.

Raoul S. Concepcion, MD, FACS: Chuck?

Charles J. Ryan, MD: Practice proactive medicine, not reactive medicine, I think is the key point, and stay attuned to the evolving knowledge of biology here because it’s moving fast. There are new molecular markers and pathways coming that will be important.

Raoul S. Concepcion, MD, FACS: Jorge?

Jorge A. Garcia, MD, FACP: I think defining your goals of treatment for that patient you have in front of you is important when you’re making treatment decisions in a crowded market with many great agents, without really knowing which is the best agent for that particular patient. And lastly, I think that chemotherapy is, in fact, the new standard of care for men with castration sensitive metastatic disease.

Raoul S. Concepcion, MD, FACS: Judd?

Judd W. Moul, MD, FACS: And I would say again now more than ever, the team approach for CRPC and also hormone-naive metastatic disease is paramount, because urologists and medical oncologists really need to partner for these patients for the best care. Both specialties clearly manage these patients and need to continue to be on the forefront of team medicine.

Raoul S. Concepcion, MD, FACS: Great. On behalf of our panel, we thank you for joining us and look forward to seeing you next time.

Transcript Edited for Clarity