When Should Chemotherapy Be Used in Metastatic Prostate Cancer?

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Questions abound when it comes to the optimal timing and sequencing of chemotherapy in metastatic prostate cancer, according to Dr. Yu. For example, arguments could be made both for using it earlier, while disease is still hormone-sensitive, or later, after hormonal resistance emerges.

“For quality-of-life reasons, many patients don’t want chemotherapy. So this is something that is probably individually based. I think it’s a worthwhile discussion with the patient,” he recommended.

Additionally, if patients are given docetaxel up front, as in the CHAARTED trial, in new metastatic hormone-sensitive prostate cancer, what is the best course of action when the disease becomes castration-resistant? “Do you go back to docetaxel for retreatment? Move on to cabazitaxel [Jevtana]? That’s not clear either,” Dr. Yu said. “There are cost considerations though. Docetaxel is off patent, so it’s certainly much more affordable than cabazitaxel.”

Castration-Resistant Disease

Another question is, what is the appropriate niche for chemotherapy in metastatic castration-resistant prostate cancer? Here, arguments could be made for using it in patients with visceral disease, given their much more aggressive course and much worse prognosis; for patients with rapidly progressive disease, as signaled by prostate-specific antigen; for patients who have primary resistance to abiraterone (Zytiga) or enzalutamide (Xtandi); or for patients with acquired resistance to either of those agents.

“None of this is clear in the field. So we really have an embarrassment of riches right now—this huge smorgasbord of options. How to choose, how to sequence, it’s very unclear in our field right now,” he commented.

Forthcoming results of a phase II trial called PRIMCAB may offer some guidance, according to Dr. Yu. Patients with primary hormonal resistance, defined as progressive disease within 6 months of receiving either abiraterone or enzalutamide, are randomly assigned to either the alternate hormonal agent or cabazitaxel.

“This is an interesting study, and it really addresses an unanswered question in the field, which is should we be moving chemotherapy earlier, especially if you have already started to show disease progression on one of these novel hormonal therapy agents,” he said. ■

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