Considerations on Tolerability of Cabazitaxel in mCRPC

Atish D. Choudhury, MD, PhD

Chair of the Gelb Center for Translational Research

Senior Physician

Dana-Farber Cancer Institute

Assistant Professor of Medicine, Harvard Medical School

Boston, MA

DISCUSSION QUESTIONS

• Has the data from the CARD trial (NCT02485691) influenced your practice? ​
• What is your approach in managing toxicities associated with cabazitaxel (Jevtana)?​
• How do you counsel patients regarding infusion versus oral options and their tolerability profiles? ​
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ATISH D. CHOUDHURY, MD, PhD: [In the CARD trial], all of these patients had docetaxel previously, and all of the patients had either abiraterone [Zytiga] or enzalutamide [Xtandi] previously, but not both. So if you had abiraterone, then on the control arm, you would get enzalutamide, and if you had enzalutamide, then on the control arm, you would get abiraterone.¹

OWEN PICKUS, DO: These are not earth-shaking data, then. It makes perfect sense that someone would progress more quickly and maybe have more adverse events [AEs] after you've re-exposed them to the same agent, but I'm not quite clear how many [physicians]…who have patients who have failed on abiraterone go to enzalutamide. That is not my standard by any means. If they failed one mechanism of action like that, I do look for other options, so of course cabazitaxel makes more sense.

CHOUDHURY: If you look at prescribing patterns out in the world, most patients with metastatic castration-resistant prostate cancer [mCRPC] are managed by urologists, and it's very common for patients to switch from abiraterone to enzalutamide or vice versa out in the community, and so [there was] an interest to demonstrate that that's not an appropriate strategy and that cabazitaxel is favored, especially for symptomatic patients.

SHEILA DONNELLY, MD: I have a major interest in breast cancer, and it has always been surprising to me that you can't switch back and forth to different hormonal therapies in prostate cancer and get results the way you do in breast cancer. I believe these data, but it leads me to the question, do we have any data on CDK4/6 inhibitors in prostate cancer with the use of various androgen depletion therapies?

CHOUDHURY: There is a phase 2/3 trial [CYCLONE 2; NCT03706365] that has not yet been reported of abiraterone plus or minus abemaciclib [Verzenio] in first-line mCRPC, and that's leading to a [larger] phase 3 trial [CYCLONE 3; NCT05288166], but we don't have those data yet in the public domain.

DONNELLY: OK, good.

CHOUDHURY: But yes, you're right on target with what we're looking at.

If you have a patient in front of you, and they received docetaxel and they received abiraterone, how would you decide on a patient for whom you're going to do cabazitaxel next? Are there some [for whom] you would consider going to enzalutamide first?

DONNELLY: I would consider it in somebody who has very indolent disease, where it might be mostly PSA [prostate-specific antigen] rising, or you're trying to delay chemotherapy. I think those are patients [for whom] you're just trying to throw in some roadblocks for a while.

KRISHNA GUNTURU, MD: My current practice, before the [introduction of] lutetium-177-PSMA-617 [Pluvicto], if there is no microsatellite instability or other treatments, and if they already received either abiraterone or enzalutamide, then I go to cabazitaxel post-docetaxel.

When we started the cabazitaxel with the [stronger] dosing, it was higher toxicity, so that's the reason we are now more seasoned to take care of these toxicities and decrease the dose. It's better to give them cabazitaxel and give growth factor support…so I always present these options.

ROBERT KOCH, MD: There was that trial that tested 25 mg/m² versus 20 mg/m² [of cabazitaxel in the] PROSELICA trial [NCT01308580]. The 20-mg dose didn't reduce the PSA levels as dramatically as the 25-mg/m² dose. However, if you looked at the imaging responses, they were equal.² So, I favor the 20-mg/m² dose, especially in people who have previously been treated with cytotoxic therapy. I think that the results are probably about equivalent. And in terms of the AEs, these patients oftentimes will need growth factor support because of their previous myelotoxic therapy. Typically, they're elderly with comorbidities, so the symptoms of fatigue, myelosuppression, and diarrhea, [for] some patients, are better managed at the lower dose, which support with single-agent paclitaxel in a patient such as this, so that's my standard practice.

CHOUDHURY: What are the AEs that you're commonly seeing with cabazitaxel at the 20-mg/m² dose, and how do you counsel the patients and manage it?

KOCH: The risks are the same as what you would expect for a myelotoxic drug. Febrile neutropenia, fatigue, cytopenias, and some diarrhea in a few patients along the way, so they get managed in a typical way. We manage these AEs [as we would for] any one of our patients who is receiving cytotoxic chemotherapy. I haven't got any tricks.

CHOUDHURY: Right, it's pretty standard. So, does anyone else have any comments that they want to make about cabazitaxel and AEs compared with the oral options?

KERRY KILBRIDGE, MD: I sometimes feel in these situations that there's a bias away from chemotherapy among patients in general, and particularly in this case, where the patients already had peripheral neuropathy with the docetaxel. Sometimes, that's what we're trying to overcome, and we persuade them towards cabazitaxel as an option.

CHOUDHURY: Yes, and docetaxel has a variety of skin changes and nail changes, and sometimes face changes, and those things are less common with cabazitaxel. The main things that we see that might be more frequent are the febrile neutropenia—though that can generally be managed with using the lower dose and the growth factors—and diarrhea does seem a bit more common with cabazitaxel, but that's usually manageable as well.

_References:

_{1. de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med. 2019;381(26):2506-2518. doi:10.1056/NEJMoa1911206}

_{2. Eisenberger M, Hardy-Bessard AC, Kim CS, et al. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in postdocetaxel patients with metastatic castration-resistant prostate cancer-PROSELICA. J Clin Oncol. 2017;35(28):3198-3206. doi:10.1200/JCO.2016.72.1076}