Practical Considerations for Sequencing Cabazitaxel in Metastatic CRPC

Centering discussion on the use of cabazitaxel in metastatic CRPC, key opinion leaders consider optimal sequencing of therapy in light of the TROPIC clinical trial.

Tanya Dorff, MD:
We are starting to get some sequencing data from some of our clinical trials, and even more directly comparative data. I think that’s a lot of what we wanted to talk about tonight. I know some people really struggle with cabazitaxel as a taxane chemotherapy, and why it can be used even after docetaxel chemotherapy, which is another taxane. How do you address those types of questions when you hear them? Or how do you picture cabazitaxel in your mind?

Elisabeth Heath, MD, FACP: This is where the studies that have emerged in the last several years have been helpful. Because you and I practice similarly, where we want the evidence to guide us; not, “Well, I think they had a pill last time. And then they had chemotherapy. So should we go back to a pill?” I think, in that sense, we now actually have data. Part of the challenge for cabazitaxel being another microtubule inhibitor is it can still cause some similar [adverse] effects, although I think it’s actually better tolerated than docetaxel. But we still have our fair share of things that we [must] worry about, like white blood cells can go down and you typically need dose factors. We worry about anaphylaxis or any type of reaction, like the day-to-day things that we would fuss about in clinic. But in terms of, “Well, when would you insert that,” I do think that it is worth our time tonight to discuss that. In your situation, based on the data out there, Dr Dorff, do you incorporate cabazitaxel after 1 NHT [neoadjuvant hormonal therapy] and a run of the docetaxel? Or do you think of something else?

Tanya Dorff, MD: That’s a great question. Even when I can’t address why it works, I can point to the TROPIC trial [NCT00417079], in which all the patients had been exposed to docetaxel. Now, at that time, there wasn’t as much abiraterone or enzalutamide around. So, we have [fewer] data, potentially, from TROPIC, about that population. But we know it works post docetaxel, even if we can’t fully explain. There are issues about how the microtubules might become resistant to docetaxel, but not cabazitaxel. But I do use it sometimes, immediately after docetaxel, following an NAH [neoadjuvant hormone] like abiraterone or enzalutamide, but not always. Patients are different. So, if we’ve done NGS [next-generation sequencing], and we have an option for a PARP inhibitor, sometimes that’s something that we might have enough confidence in, that we would place it in first. But TROPIC was…compelling. We saw survival prolongation. Now, this was compared to mitoxantrone, so it was not a placebo. It has a relatively active comparator. The median progression-free survival was short, but that was in an era where we didn’t have a lot of other treatment options, so that would look different today. As you mentioned, neutropenia is something that we obviously worry about. The TROPIC trial was dosed at 25 mg/m2. And in that context, grade 3 neutropenia was 82%. But these days, many of us might use different dosing. The good thing is neuropathy is one that is less overlapping with docetaxel, so that’s where a patient might say, “No, I already have neuropathy. I don’t want another chemotherapy, another taxane.” And we can reassure them that the rates of neuropathy were quite low. They were less than 10% in that TROPIC trial. You don’t see people just falling apart or deteriorating. Performance status seems to be maintained. And I [must] remind patients, “A lot of your symptoms are really coming from cancer, at this point, and chemotherapy, when it’s working, can actually make you feel better,” which is so counterintuitive.

Transcript edited for clarity.

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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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