ORLANDO, FL, USA (UroToday.com) - This study addresses the immune response and sequencing of sipuleucel-T and abiraterone acetate for the treatment of asymptomatic and minimally symptomatic mCRPC patients (n=29).
Of the two arms, concurrent (n=16) and sequential (n= 13) all but two patients received three infusion cycles of sipuleucel-T. Two men received just one infusion due to insufficient total nucleated cell (TNC) counts (n=1) and disease progression eight days after randomization (n=1). The primary endpoint of this study was cumulative CD54 upregulation (the measure of antigen presenting cell activation), with secondary and tertiary endpoints of CD54+ cell and TNC counts, safety, and efficacy. Of the two arms, no significant differences were noted in CD54 upregulation. The second and third infusions of sipuleucel-T were “indicative of a prime boost effect” for both arms. The researchers concluded the humoral and cellular immune responses to sipuleucel-T were similar with concurrent or sequential AA plus prednisone.
Listen to Eric J. Small, MD discuss the study
“We know that both abiraterone acetate and sipuleucel-T (Provenge®) have activity in prostate cancer. We don't know how to sequence them. One of the concerns about adding an agent such as abiraterone is the concurrent use of prednisone. The question is whether it is immunosuppressive or not.
“So the way we addressed this was to do a multi-center (study), currently a 60-patient randomized phase II study in which patients were randomized to receive sipuleucel-T with concurrent abiraterone acetate and prednisone, or sipuleucel-T followed after its administration by abiraterone acetate for the same length of time. The endpoints of this study were to look at: product characteristics of the agents to see if it was effective with the concurrent use of steroids, because sipuleucel-T is produced every 2 weeks by freezing the patient's cells. So the question is, with prednisone on board, does that change the product characteristics? Then the second issue is, down the line, as you measure immune responses, are those effective? The immune responses are checked up to six-weeks later.
“The upshot was that the result showed that if you looked at CD54, (CD54 up-regulation is a marker of Provenge activation) there is no difference whether the patient received concurrent prednisone or not. Similarly, if you look at immune responses, be it antibody responses, T-cell proliferation responses, or ELISPOT responses, in all but one case, you see both the six-week up-regulation in both arms (of the trial). So the prior use of prednisone did not resolve in a subsequent inability to launch an immune response to either the fusion protein or PAP, its target protein. This result suggests that at least by these immune parameters, there’s no difference, and there is no downside to the concurrent use of abiraterone, and more importantly, prednisone along with sipuleucel-T.”
Dr. Small also indicated that there was no difference in the safety parameters in the two arms of the trial. This study does not provide outcomes in terms of survival because “the study is very early, but also completely underpowered to look at survival.” However this study does address immune responses including CD54 up-regulation which in the pivotal Provenge study did correlate with survival. “So, our hope is that by showing that's there's no difference, that in fact survival would be the same, and that these agents can in fact be used together. Right now, the clinical implications of (this data) is that since enzalutamide is not approved in the pre-chemotherapy space, that for pre-chemotherapy patients who get Provenge and subsequently get abiraterone acetate, that it's probably fine to do that and it's probably fine to do it at the same time.”
Presented by Eric J. Small,* Raymond Lance, Thomas A. Gardner, Lawrence Ivan Karsh, Andrew Stubbs, Candice McCoy, Todd DeVries, Charles H. Redfern, Neal D. Shore at the 2013 Genitourinary Cancers Symposium - February 14 - 16, 2013 - Rosen Shingle Creek - Orlando, Florida USA
*University of California, San Francisco, San Francisco, CA; Eastern Virginia Medical School, Norfolk, VA; Indiana University School of Medicine, Indianapolis, IN; The Urology Center of Colorado, Denver, CO; Dendreon, Denver, CO; Dendreon Corporation, Seattle, WA; Oncology Associates of San Diego, San Diego, CA; Carolina Urologic Research Center, Myrtle Beach, SC
Prepared by Karen Roberts, medical writer for UroToday.com