Treatment Options in Metastatic Castration-Sensitive Prostate Cancer - Episode 8

Sequencing in mCSPC

A prostate cancer expert shares rationale for his preferences and choices while sequencing therapies in prostate cancer.

Atish Choudhury, MD, PhD: How does long-term data affect our choice of sequencing? I would say that this is a very controversial topic, and I do have my own preferences in this particular setting; though there’s not really any prospective data in the castration-sensitive setting about sequencing 1 agent followed by another and seeing which one leads to the best outcomes.

What I would say is that the PEACE-1 study and the ARASENS study do suggest that using abiraterone or darolutamide in combination with docetaxel is superior to using docetaxel first and adding the second agent at the time of progression.However, what it doesn’t answer is can you do docetaxel first and then immediately transition to the other agent before progression and get the exact same benefit?We don’t know the answer to that question at all.

What I would say is that the Level I evidence is with simultaneous treatment, but for patients concerned about toxicities, and particularly overlapping toxicities like LFT [liver function tests] abnormalities with abiraterone and docetaxel, it wouldn’t be unreasonable to start 1 and then the other. But I certainly would not recommend waiting for progression before starting the second agent.

For patients who are not receiving docetaxel, I think that it’s fair to say that for patients who progress on enzalutamide or apalutamide, the likelihood of response to abiraterone afterwards is much lower than if you started with abiraterone and used one of the other agents second.

Now, whether that’s meaningful in terms of overall survival hasn’t really been demonstrated, but again, because of the more favorable cost of abiraterone as a generic, and because of better quality of life in some patients with abiraterone in terms of the cognitive issues and risk of falls, that does tend to be my favorite first-line agent over the others, so the others are absolutely reasonable if you have a contraindication to abiraterone. Certainly, if they’re well covered by insurance, then cost is much less of an issue.

So, I would say that every practitioner has their own preferences.There are some concerns with long-term risks of abiraterone in terms of cardiovascular events, and whether avoiding abiraterone and using one of the other agents decreases that risk is also not known.So, I would say that that whole answer is really based on my own personal perspectives and biases, but if somebody has a different preference for a sequence, again, there’s really very limited data to guide, which is really optimal.

Transcript edited for clarity.