Mary-Ellen Taplin, MD, shares her method for selecting and dosing chemotherapy for metastatic castration-resistant prostate cancer.
Jorge A. Garcia, MD, FACP: Mary-Ellen, I’d like to get back to your comment about your choice for cabazitaxel. As you know, Dr Christopher Sweeney, through the ECOG group, put the data together with Dr Gwenaëlle Gravis from the French system in their up-front chemotherapy trial. We showed that when you rechallenge patients with docetaxel after they have received docetaxel-based therapy, they didn’t get a lot of improvement. Most of us would argue cabazitaxel. But I’d like to ask you the question. We have very compelling data, to some extent, that you don’t need to start cabazitaxel at 25 mg/m2. If you look at the PROSELICA data, at the noninferiority of 20 mg/m2 compared with 25 mg/m2, it does appear that 20 is not inferior. In your practice, do you use the 25 mg/m2, or have you moved from 25 to 20 mg/m2?
Mary-Ellen Taplin, MD: We use only 20 mg/m2. There was a prospective large trial that the FDA made them do that showed no benefit to higher dose. So we use 20 mg/m2, without GM-CSF support or G-CSF [granulocyte colony-stimulating factor] support unless the patient has concern for more serious than average neutropenia. So we use 20 mg/m2.
Jorge A. Garcia, MD, FACP: Great. Mary-Ellen, if I had biopsied this patient and this patient had some neuroendocrine elements, what would have been your choice of chemotherapy? There are a lot of people enthusiastic about giving PARP inhibitors for that type of patient. But what would be your thought about the choice for chemotherapy for this neuroendocrine differentiation, should this patient have such?
Mary-Ellen Taplin, MD: For chemotherapy, I have several things that I use. We could use cabazitaxel plus carboplatin. Sometimes I use carboplatin alone or docetaxel and carboplatin. There are no data to support 1 over the other. Sometimes I have a particular clinical situation like a patient who’s had a docetaxel-infusion reaction, and maybe I’d give them carboplatin alone. If a patient has never seen cabazitaxel, I might give them cabazitaxel and carboplatin. I use a lot of carboplatin in dedifferentiated prostate cancer.
Jorge A. Garcia, MD, FACP: Patrick, you work with Dr Ana Aparicio and Dr Paul Corn [at The University of Texas MD Anderson Cancer Center]. To some extent, that regimen of carboplatin-cabazitaxel was actually generated by your group. Is that something that you commonly do? When you talk about the anaplastic phenotype, some of these patients are getting that combination even earlier once they become castration-resistant early on, but not without having seen an oral agent.
Patrick G. Pilié, MD: Yes, absolutely. There are clinical definitions of aggressive variant prostate cancer or more anaplastic differentiation, as well as the trials of carboplatin with cabazitaxel. There’s particular benefit in patients that display the aggressive variant prostate cancer molecular signature, which involves aberrations in TP53, RB1, and PTEN, 2 of 3. The patients who have more rapid progression on the second-generation antiandrogens combined with molecular features push us to add in the platinum-based agent of carboplatin with cabazitaxel very frequently.
Jorge A. Garcia, MD, FACP: Would it be fair to assume for the group that should this patient have received an oral agent, ie, TITAN, ENZAMET, LATITUDE with abiraterone, enzalutamide, or apalutamide, that the sequence upon progression would have been docetaxel? Mary-Ellen?
Mary-Ellen Taplin, MD: For this particular patient with the liver metastasis? Yes. In my practice, in a more indolent patient without visceral disease, I might try enzalutamide after abiraterone, understanding that the response rate is 25% to 30% and generally can be short lived.
Jorge A. Garcia, MD, FACP: For our audience, it’s super important to recognize that NGS [next-generation sequencing] testing is critical for these type of patients—certainly in this setting. Not only can you capture DNA-repair deficiency and whether it’s a germline or a somatic change, which can get you up to 25% or 30% of patients, but also checking for microsatellite instability [MSI] based on the unrestrictive label for nivolumab and pembrolizumab for people with MSI-high disease, in tumor-agnostic specifically. And now with pembrolizumab with TMBs [tumor mutational burdens] greater than 10%. It is part of our clinical practice that we look at genomic sequencing for these patients, sometimes up front. But certainly in this patient if this patient hadn’t seen it before. Most of us would be all over that as well.
Transcript edited for clarity.
The RAPSON trial found that receiving radium-223 prior to docetaxel in patients with metastatic castration-resistant prostate cancer improved quality of life and tolerability compared to the reverse sequence, without affecting progression-free survival or overall survival.
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