What will happen when enzalutamide (Xtandi) is approved for use in advanced prostate cancer in the disease stage prior to chemotherapy (that is if it is approved)? Already occupying this space and already approved by the FDA is both Provenge and abiraterone (Zytiga). Where will Xtandi fit in?
Until we have a lot more data, which will inform our doctors, we can only guess what the optimum treatment sequence should be to provide the longest survival opportunity. So, here is my guess and my rational for my guess.
The first FDA approved treatment used should be Provenge (although I personally would participate in the ProstVac trial before moving to Provenge, but I would move to Provenge the day I completed the trial). Provenge takes time to work and will be most effective while the PSA is low. The lower the better, so Provenge should be the first treatment used when a man becomes castrate resistant.
After completing the three Provenge infusions doctors will be faced with a decision to use either Xtandi or Zytiga. We do know that both drugs do cause some degree of cross-resistance to the other; this needs to be weighed in the decision process. Xtandi is more expensive than Zytiga. So, which drug t o use?
My vote is for Xtandi, despite its higher cost. Xtandi does not require the simultaneous use of a steroid while Zytiga does require a steroid. More importantly, in the Phase 3 trial of Xtandi, Xtandi had a 29% reduction of risk of death compared to 21% for Zytiga. Better survival possibilities equal a better treatment when all other factors are equal.
All of this discussion doesn’t take into the possibility of combining both Zytiga and Xtandi as a better treatment option.
Could I be wrong, of course I might not be correct. It is possible that the insurance companies aggressive moves to Step Therapy will force doctors to use the less expensive drug Zytiga first, but I don’t believe that this is the best direction for us men with advanced prostate cancer.
Joel T. Nowak, M.A., M.S.W.
I lean that way too, Joel. After receiving Sipuleucel-T last summer (through a tunneled Palindrome catheter!), we gave Provenge until Christmas to work alone. My PSA’s rise, though small, was doubling each month. I held my medical oncologist off on starting abiraterone – hoping for the FDA approval of enzalutamide until May when it was obviously time to begin. That week I discovered a clinical trial @ NIH that offered enzalutamide to both arms (plus Prostvac to the arm I ended up in) and was fortunate to be enrolled quickly. I really did want enzalutamide first.
How about Radium 223 (Xofigo) where does it fit in? Particularly for men with only bone metastasis. Also I have heard Provenge may be in financial trouble? Any truth to this?
Ron, If you look in the blog earlier I had strongly suggested that people consider doing exactly what you ave done. First, get Provenge, then enter into the Prostvac trial. – Joel
Dendreon (the makers of Provenge) have been in financial trouble for a long time. Many of us continue to hope that they work through their issues as this is a vial and very much needed treatment which will only harm us if it disappears. At this moment I would reserve Radium 223 for after both Zytiga and Xtandi have failed. The exception would be for men who have many bone mets which are causing very severe and debilitating bone pain. Again, this is my opinion and I am not a doc.
Joel–I thought you couldn’t enter into the Prostvac trial if you had previously had Provenge. Has that changed?
Damon, You are 100% correct, the post was written from the perspective of currently approved FDA treatments, but I did decide thanks to your comment to add my strong personal preference for moving into the trial first then on to the FDA treatments. Thanks – Joel
Thanks for the shout out. It helps to get feedback – Joel
Joel, it turns out I was only 50% correct about the Prostvac trial/Provenge sequence. I recently met with the principal investigator on the Prostvac/enzalutamide trial mentioned in the first post above (NCT01867333), and he didn’t have any objection to having Provenge first, then the trial; in fact that’s what he recommended. Apparently other Prostvac trials like NCT01322490 do exclude you if you’ve had Provenge. So you have to be careful and read the individual criteria for each trial you are considering.