The Future of Metastatic Castrate-Resistant Prostate Cancer Management


An expert discusses the future of metastatic castrate-resistant prostate cancer management.

Karim Fizazi, MD, PhD: For men with metastatic castration-resistant prostate cancer [mCRPC], things are rapidly evolving, and we now have more weapons to treat these patients. I suspect that very soon, at least in rich countries, many men will receive an AR [androgen receptor] drug early in the course of the disease. Therefore, if a patient develops metastatic CRPC, they will have already exhausted those agents such as abiraterone, enzalutamide, darolutamide, or apalutamide, and we will need other agents to treat patients. Based on the PEACE-1 trial, some of these men also will have exhausted docetaxel chemotherapy.

We will have to decide on other compounds. Obvious options will include cabazitaxel, radium-223, and also PARP inhibitors and lutetium-177 PSMA-617, assuming all of these agents are available and reimbursed in places where patients live. Some other compounds may find their ways to the market. We’re waiting from more data regarding AKT targeting in men with PTEN loss. Randomized phase 2 data are very appealing with these agents, and some early phase 3 data are supporting efficacy. We need longer-term data. We’ve seen promising data from early phase 1 with various third-generation androgen receptor antagonists that seem to work in men failing abiraterone or enzalutamide. Hopefully we will soon have phase 3 trial starting to see whether this is true in a larger population of men. For patients with mCRPC, things are changing. More and more we will not use abiraterone, or enzalutamide, or similar agents, because these agents will have been used earlier for better outcomes and for a longer time without disease progression and longer life, as demonstrated in the M1 castration-sensitive disease and in the M0 CRPC setting. We will use different agents, which is excellent for patients because it means that we will show efficacy from these agents in this setting.

In conclusion, for men with metastatic castration-resistant prostate cancer, the last decade has been truly exceptional. We’ve seen a number of agents with tremendous efficacy, including overall survival improvement, and years of overall survival improvement in some spaces. Some of these agents have different mechanisms of action and some of them are not cross-resistant, which means that we can either combine when the safety allows us to do so, or sequence them when we cannot or when the evidence for combining is not there, or not yet there. We have more options to propose to patients, and more are coming. I hope that the next decade will be similar and will provide us as many advantages and as much progress as we saw in the last decade. I’m confident to be honest. Thank you very much.

Transcript edited for clarity.

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