I have said many times that one of the more important issues facing our use of Provenge is when to start it and how to sequence this treatment with the other newly approved agents that have recently become available for men with advanced prostate cancer. There is occasional conversation that Provenge is already antiquated due to the approvals of Zytiga (abiraterone) and Xtandi (MDV31000), but this is not true!

Looking at oncology in general, the sequencing of treatments and the co-administration of treatments is very much the norm and there is no reason to believe that this should be any different in treating men with advanced prostate cancer. Provenge is not antiquated, but we need to find the proper scheduling of all our new treatments.

In the strange but real events in the treatment of prostate cancer, Zytiga is often used instead of Provenge, despite the fact that Zytiga failed to extend survival (COU-AA-302). What probably makes more sense that in men where their disease load is still small and not growing quickly the better first drug is Provenge.

According to The Journal of Clinical Oncology:

“The practical dilemma of the appropriate sequence of use of the two new noncytotoxic agents (sipuleucel-T and abiraterone) is being addressed by trials that are under development. For now, given the broader window of applicability of abiraterone and the longer time required to develop an immune response with sipuleucsipel-T, if both agents are to be used, it seems reasonable to administer sipuleucel-T first with Abiraterone after additional disease progression. Biomarkers to help define the optimal use of immunotherapy are needed.”

I would take this conclusion even one step further. I would suggest that a better recommendation would be for men with advanced prostate cancer and with a low disease burden should be given Provenge (sipuleucisipel-T) first and quickly as they become castrate resistant. What I am recommending is that the words “if both agents are to be used” be removed.

Happily, Dendreon currently is running a sequencing trial involving both Provenge and Zytiga. This trial is designed “to evaluate the impact of concurrent versus sequential administration of abiraterone acetate plus prednisone on product parameters of sipuleucel-T, and to assess the safety and efficacy of sipuleucel-T with concurrent or sequential administration of abiraterone acetate plus prednisone in men with metastatic castrate resistant prostate cancer.” Results of this trial are anticipated to become public at the end of 2013.

The concurrent administration of Provenge and Zytiga raises the concern that Zytiga requires co-administration with prednisone, which compromises the patient’s immune system. Currently protocol calls men who are given Zytiga first to wait for a 60-day period after completing their Zytiga regimen before Provenge can be administered (allowing a washout period). This study should shed more light on this issue.

Until we see the results of this trial, I believe that Provenge should be used as early as possible once one qualifies for the treatment. Reinforcing this argument is the quartile study, published last year, which showed that for a men with a Baseline PSA less than or equal to 22.1, the median life extension benefit is a stunning 13.0 months. For a Baseline PSA between 22.1 and 60.1, the median life extension benefit dropped to a still respectable 7.1 months. Clearly, when it comes to using Provenge, the earlier, the better!

Joel T. Nowak, M.A., M.S.W.