An Overview of Metastatic Castrate-Resistant Prostate Cancer


Karim Fizazi, MD, PhD, provides an overview of advances in treatment of metastatic castrate-resistant prostate cancer.

Karim Fizazi, MD, PhD: In the last years, we’ve seen tremendous progress for men with metastatic castration-resistant prostate cancer. If I look at the last decade, we were able to show that using a next-generation hormonal agent was associated with improvement in overall survival in these men, and this was true pre- and post-chemotherapy. The same drugs have been used up front, either in the nonmetastatic castration-resistant prostate cancer space or in the M1 castration-sensitive prostate cancer space, with a greater benefit for the patients.

On top of that, cabazitaxel, a second taxane, was shown to be active even when the first one was not anymore. Bone-targeting agents have shown benefit for patients. This is true for denosumab…in terms of protecting patients from fractures and other skeletal-related events. Radium-223 was also associated with overall survival improvement. More recently, we showed that targeting PSMA [prostate-specific membrane antigen] with lutetium-177 PSMA-617 was also associated with overall survival improvement, even when everything else failed. Also, for a subgroup of men with BRCA1 and BRCA2 alterations, PARP inhibitors can prolong life. More progress is likely to come.

When a patient develops metastatic castration-resistant prostate cancer, several factors need to be considered before making decisions. One very important one is whether a patient has received ADT [androgen deprivation therapy] alone, which used to be the standard of care years ago, or whether they have received intensification of treatments. Of course, this is now changing the field. We see more patients who have exhausted the first AR [androgen receptor] drugs, such as abiraterone, enzalutamide, darolutamide, or apalutamide when they develop metastatic castration-resistant prostate cancer. Because the cross resistance between these 4 agents is very high, they’re unlikely to work after one of them has already failed.

This is obviously something very important we consider, and in these men, actually taxane chemotherapy is probably the main standard of care. We’ve also demonstrated that for patients who have failed both AR-targeting next-generation hormonal agents plus 1 taxane, we now have at least 2 options with cabazitaxel, a second taxane, and more recently lutetium-177 PSMA-617, which are both associated with improvements in radiographic progression-free survival and overall survival.

We need to dig into details of the biology of the disease, and we now have evidence that choosing a PARP inhibitor, olaparib, in men failing these agents when they have BRCA alterations, overall survival is improved. All of those things need to be considered, of course on top of the usual parameters of performance status and patient’s preference.

Transcript edited for clarity.

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