Metastatic CRPC: Considering Use of Combination Cabazitaxel/Carboplatin

Switching their focus to combination therapy in metastatic CRPC, expert oncologists review trial results from a study analyzing cabazitaxel/carboplatin therapy.


Tanya Dorff, MD: There’s so much talk about combinations. With cabazitaxel, there’s been a look at some of these more aggressive variants and adding platinum. What do you think about the work MD Anderson [The University of Texas MD Anderson Cancer Center, Houston, Texas] is doing combining carboplatin with cabazitaxel?

Elisabeth Heath, MD, FACP: Yeah, the good part was this: They had a phase 1 trial with Dr Paul Corn [internal medicine specialist at MD Anderson] and Dr Ana Aparicio [oncologist at MD Anderson]. We had the privilege to do that study with them and get an earlier glimpse of how to work that. I was surprised at how well-tolerated this combination is. You’re almost thinking, “You’re going to pile on carboplatin at an AUC [area under the curve] of 4, are you kidding me?” But I think about the structure of who the patients were. Again, asking who are you going to pick, I think it lends itself to [patients with] this more aggressive variant. And they defined it in quite broad terms, basically visceral met [metastasis] or mostly lytic bone met, which on occasion we see instead of blastic or super-low PSA [prostate-specific antigen] that makes you think, is it more neuroendocrine- [like]? Even if it wasn’t neuroendocrine, I think there’s a sense of the really aggressive drugs, sometimes with the Gleason 10s, [when] I will also add carboplatin. This paper was really helpful to us because it allowed us to reference it so that from an insurance standpoint, which you may think,“[Carboplatin] is really cheap these days, [it’s] been around for decades,” but [insurers] can’t process [the combination] because they don’t belong together. They don’t understand.I believe that the January 2023 version of NCCN [the National Comprehensive Cancer Network] has incorporated that now. If you go on [the NCCN website], it’s there as another option, which has really helped. But what I do now is more combinations than single agents. Again, I’m just surprised at how safe and reasonably tolerable it is, and [it’s] very powerful in terms of the responses. I’ve really adopted it for the patients who you’re like, “Gosh, there’s a lot of disease in all the wrong places, and the PSA is low.” I have several patients who are predominant lytic metastases, so much so that we’re almost biopsying to make sure it’s still prostate [cancer] because it’s so unusual. But I have used the combination.

Tanya Dorff, MD: I’ve also used it a little bit even outside of trial. I agree with the fact that it is more tolerable than I might’ve imagined. There’s definitely more nausea than we’re used to dealing with our taxanes. But what I find interesting is, at least in my experience, some of these treatments for emerging neuroendocrine prostate cancer patients, or these aggressive-variant patients, almost seem to do better with cabazitaxel and carboplatin and platinum etoposide. I’ve had insurance companies that have denied the [cabazitaxel] andthen platinum’s in there with etoposide and the patient didn’t respond, I was then able to access the [cabazitaxel-carboplatin] in that. I don’t know if there’s a special synergy in the combination or if it’s just that prostate cancer despite having your endocrine phenotype. Still, it’s just a really taxane-sensitive type of malignancy. I don’t know if that’s been your experience. And I know this is anecdotal, but I find it interesting.

Elisabeth Heath, MD, FACP: Yeah, that’s been my experience, too. I wish we could fast-track it, to tell you the truth. I think carbo-etoposide is very active; it’s just by the time it’s there, it’s just wearing down bone marrow, and then we’re just hoping that this will stand. I know sometimes I will also look at their sequencing. So most of them now have been sequenced at least for their somatic metastatic areas. And we look at unfavorable things like TP53 or RB1 or P10 loss. When I see that I’m almost more motivated to give this because that’s the group that has such aggressive cancer that there’s only finite time before the disease gets away from us.

Tanya Dorff, MD: And what’s so cool is that there are now clinical trials that acknowledge that exact signature, those TP53, RB1, P10 loss patients. If you look, there are trials that we have with an immunotherapy drug added on top of cabazitaxel and carboplatin. So, the work that MD Anderson did on that front has just been so influential.

Elisabeth Heath, MD, FACP: I wonder now that we’ve got all these changes in the hormone-sensitive space and a lot of this is happening right up front, do you think that’ll help us with this cabazitaxel alone or in combination with the carboplatin? Do you think that’s going to change how we’re doing this?

Tanya Dorff, MD: It has the potential to move cabazitaxel up earlier in the disease. Although, it is really a semantic definition. It might be first-line mCRPC [metastatic castration-resistant prostate cancer] because someone got docetaxel and abi [abiraterone] up front. But, it’s really post docetaxel and post abiraterone, in my view. It’s really about, what are your prior treatment exposures? To me, that’s a little more meaningful than first-line mCRPC, or second-line mCRPC. So, I’m not sure that cabazitaxel moving earlier is really earlier. There’s a lot we have to figure out because the landscape has changed so quickly. People do talk about using a docetaxel rechallenge in this new landscape of having up-front docetaxel and then maybe a fairly long remission before there is resistance and needing a new treatment option. But I really love the fact that once they’ve gone through that up-front docetaxel, I don’t have the docetaxel rechallenge; I can just go right to the cabazitaxel, which, as you mentioned, from FIRSTANA [NCT01308567] and other studies does seem to be better tolerated and sometimes easier to get patients to agree to, especially since they tend not to lose their hair, which is big.

Elisabeth Heath, MD, FACP: That’s a very big deal. I think that does help us.

Transcript edited for clarity.

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Evan Y. Yu, MD, professor, medical oncology, assistant fellowship director, University of Washington School of Medicine, professor, Clinical Research Division, clinical research director, Genitourinary Medical Oncology, Fred Hutchinson Cancer Center, medical director, clinical research support, Fred Hutchinson Cancer Research Consortium
Michael A. Carducci, MD, professor of oncology, AEGON Professor of Prostate Cancer Research, Johns Hopkins Medicine
Michael S. Cookson, MD, MMHC, professor, chairman of urology, University of Oklahoma College of Medicine, chief, Urology, Stephenson Cancer Center
Andrei H. Iagaru, MD, professor of Radiology - Nuclear Medicine, chief, Division of Nuclear Medicine and Molecular Imaging, Stanford University Medical Center
Jeremie Calais, MD, MSc, assistant professor of nuclear medicine and theranostics, David Geffen School of Medicine, University of California, Los Angeles (UCLA), UCLA Health,
Tanya Dorff, MD, medical oncologist, associate clinical professor, Department of Medical Oncology & Therapeutics Research, City of Hope
Matthew Rettig, MD, chief, hematology-oncology, VA Medical Center, professor of medicine and urology, David Geffen School of Medicine, University of California, Los Angeles (UCLA) Health
Tian Zhang, MD, MHS
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