I've updated this article about the importance of timing in prostate cancer therapies with the early results of the "CHECKMATE 650" clinical trial that combined nivolumab (Opdivo) and ipilimumab (Yervoy). Only 25% of men with mCRPC who hadn't yet had chemo had any early response (and only 10% of men who had had chemo). This is better than the "no response" when used alone, but worse than the response seen by either when used separately for melanoma (the recurrence-free survival (RFS) rate at 18 months with Opdivo was 66.4% and 52.7% for Yervoy (ipilimumab)). It is too early to say whether there will be any change at all in recurrence-free survival or overall survival in prostate cancer patients. The toxicity of the tested combination was unacceptably high, and several deaths due to treatment occurred.
Comparing the men who had some early response to those who didn't, it appears that the cancer had to advance to a point where there was a high mutational burden and the PD-L1 protein appeared on more than 1% of cancer cells. So it seems that for a combination of these checkpoint inhibitor-type immunotherapies, later use may be preferable to early use.
Thanks for posting this, Allen. I've seen little to suggest that the time and expense of Provenge are worth it. I know that much, much research is underway to develop precision medicines to tackle MPCa. Let's hope this work bears fruit in the years to come.
I think Provenge can help, particularly in conjunction with radiotherapy (SBRT particularly) or with chemotherapy. Those therapies make available a lot of cancer antigens that the amped up immune cells can be activated with, increasing the abscopal effect.
But I also acknowledge Provenge's shortcomings - it doesn't reduce PSA or slow progression measurably, but it does increase survival. Naysayers point out that the apparent increase in survival was caused by the depleted dendritic cells in the control group because their dendritic cells weren't incubated in the same way. They have a point, but the body does naturally replace the depleted dendritic cells pretty quickly.
Understood. I add that some medical insurance will not cover Provenge prior to other therapies, even though, according to the Prostate Cancer Foundation, "Sipuleucel-T (Provenge®) is a cell-based prostate cancer vaccine that has been approved by the FDA for men with metastatic hormone therapy resistant prostate cancer. This treatment is meant for men with minimal or no pain, and is most commonly given before chemotherapy, although it appears to be effective in some men even after chemotherapy."
I don't know if the best timing with SBRT is before, during or after. Since there are 3 infusions, i figure - why not do one of each? In conjunction with chemo, there is more time, and the immune boost (with GM-CFS) is similar to what is often given to turn-around neutropenia from chemo anyway. I haven't seen any pushback from insurance as long as the man is metastatic and castration-resistant.
I'll add my voice to the chorus of appreciation. I've learned much from this forum, and TA in particular. Knowledge is essential as we navigate our way through this journey and interact with our medical teams.
Kudos from me as well. I would be remiss not to complement you on all the information you provide for us. Thank you!
This post is relevant for me as Provenge or Xtandi are the two treatments my MO mentioned as my next options to consider on March 6th.
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Radiotherapy (Radiation) To The Primary Tumor Benefits Men With Prostate Cancer Who Have Distant Metastasis at Diagnosis 
initial treatment Locally advanced combo therapy results compared
