From Bench to Bedside: Bringing Immunotherapy Into the Clinic
Cancer Control Journal January 2013
Building on Sipuleucel-T for Immunologic Treatment of
Castration-Resistant Prostate CancerNeal D. Shore, MD, FACS, Constantine A. Mantz, MD, Daniel E. Dosoretz, MD,
Eduardo Fernandez, MD, PhD, Francisco A. Myslicki, BA, Candice McCoy, MD,
Steven Eric Finkelstein, MD, and Mayer N. Fishman, MD, PhD
" Within the context of the current metastatic CRPC treatment paradigm, points at which sipuleucel-T may
be integrated could be defined as follows:
directly after androgen deprivation therapy (ADT) failure, after failure of secondary hormonal therapy and prior to docetaxel therapy, or after docetaxel therapy..There is a rationale for concurrent use of sipuleucel-T with agents such as bicalutamide, nilutamide,
estrogen, or low-dose ketoconazole without hydrocortisone. To begin, there may be some desire to
induce PSA responses in early settings, which could be accomplished with hormone therapies. Additionally,
there is evidence suggesting that ADT may have effects on the immune system, which could enhance the activity of sipuleucel-T and other immunotherapies...
Although sipuleucel-T is likely to be most effective in the predocetaxel setting, data from the phase III clinical trials have shown that patients who have received prior docetaxel should not be precluded from sipuleucel-T treatment. In the IMPACT trial, 15.5% of patients received docetaxel prior to sipuleucel-T.15 Data from a subanalysis of these patients suggested that those who received prior docetaxel are capable of generating immune responses and may experience a survival benefit...
Could patients in the premetastatic setting respond differently to sipuleucel-T compared with patients
with metastatic disease? Based on the exploratory analyses described here, it seems possible that such
patients would derive greater beneft than those whose disease has already progressed to metastatic
CRPC.
As highlighted previously, studies of sipuleucel-T in patients with nonmetastatic prostate cancer
and a rising PSA level (PROTECT [NCT00779402] and P10-2 [NCT01431391]) and in the neoadjuvant setting NeoACT [NCT00715104]) are underway...For the IMPACT trial, 64% of control subjects (n= 109) crossed over to receive APC8015F (frozen sipuleucel-T). The median OS for control subjects who crossed over compared
with those who did not was 23.8 months vs 11.6 months. Of note, subjects who received APC8015F
had more favorable prognostic features than did those not receiving APC8015F. Subsequent analyses adjusting for prognostic factors around the time of disease progression still revealed a positive treatment effect for APC8015F. Thus, it is possible that the true magnitude of OS difference was underestimated in
the primary analysis of the phase III trial results..."www.moffitt.org/research--clinical-trials/cancer-control-journal/from-bench-to-bedside-bringing-immunotherapy-into-the-clinicPost Edited (HOPENEVERDIE) : 1/15/2013 2:10:56 PM (GMT-7)