Targeting PSMA in Advanced Prostate Cancer - Episode 2

Current Approaches for Patients With mCRPC

,

Oliver Sartor, MD, reviews the treatment approaches that are currently available for patients with metastatic castration-resistant prostate cancer (mCRPC).

Ulka N. Vaishampayan, MD: Moving on, let’s talk about the background on which we’re trying to develop these novel therapies. Oliver, can you review the available treatment options for patients with metastatic CRPC [castration-resistant prostate cancer]?

Oliver Sartor, MD: Sure. The way I like to look at it is we have a couple of hormones, abiraterone and enzalutamide, for metastatic CRPC. We have a couple of chemotherapies, so JAKs, in the frontline setting and cabazitaxel in the second-line chemotherapy setting. We have a radiopharmaceutical, radium-223, that has been shown to prolong survival. We have a couple of other older radiopharmaceuticals that are FDA approved: samarium-153, TMP [thymidine monophosphate], and things like strontium-89, but they are not used very much today.

We have immunotherapy in the form of sipuleucel-T. Then we have the precision medicines that I’ve mentioned, which are PARP inhibitors and pembrolizumab. I specifically mentioned pembrolizumab and the MSI [microsatellite instability]-high, high TMB [tumor mutational burden], and mismatch repair deficiency. That’s the current menu.

When it comes to sequencing, we get into a whole different discussion. Many patients are liable to go on the hormones first and the chemotherapies second. Cabazitaxel has become a third-line agent, particularly on the basis of the CARD trial published in the New England Journal of Medicine. The CARD trial looked at back-to-back hormones, abiraterone post-enzalutamide and enzalutamide post-abiraterone, compared with cabazitaxel in the post-docetaxel setting. It turns out, cabazitaxel is better. Nevertheless, those are our basic landscapes that we have to keep in mind as we move forward. 

Ulka N. Vaishampayan, MD: Yes. You brought up a really important point: the sequence matters quite a bit. Interspersing chemotherapy between the 2 oral hormonal compounds did make a survival difference. That is something to keep in mind.

Transcript edited for clarity.