(ChemotherapyAdvisor) – Concurrent administration of the immunostimulatory agents sipuleucel-T and abiraterone acetate (AA) plus prednisone results in sipuleucel-T potency and prime boost similar to that of sipuleucel-T alone in men with metastatic castration-resistant prostate cancer (mCRPC), an interim analysis reported during the 2013 Genitourinary Cancers Symposium in Orlando, FL.

The randomized phase 2 open-label study evaluated concurrent or sequential AA plus prednisone to determine whether increased suppression of the androgen axis with AA could provide synergy when combined with sipuleucel-T.

The concern was that “abiraterone acetate is given with prednisone, which may be immunosuppressive,” noted lead author Eric J. Small, MD, Chief of the Department of Medicine in the Division of Hematology/Oncology and Associate Director of Clinical Sciences at the UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, and colleagues.

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A total of 29 patients with asymptomatic or minimally symptomatic mCRPC were enrolled and randomly assigned to receive three infusions of sipuleucel-T at approximately 2-week intervals with up to 26 weeks of AA 1,000 mg/day plus prednisone 5 mg twice daily starting 1 day after the first sipuleucel-T infusion (concurrent arm; n=16) or at week 10 (sequential arm; n=13).

“The primary end point was cumulative CD54 upregulation (measure of antigen presenting cell activation); secondary and tertiary endpoints included CD54+ cell and total nucleated cell (TNC) counts (measures of product potency), safety and efficacy,” the investigators stated.

Of the 29 patients, 27 received all three infusions of sipuleucel-T. Two patients in the concurrent arm received only one infusion, one because of insufficient total neutrophil count (TNC) and one as a result of disease progression 8 days after randomization.

No significant differences between the concurrent and sequential arms were observed in median cumulative CD54 upregulation (31.6 vs. 36.6, respectively) and CD54+ count (1.9 vs. 2.1 x109).

“Increased CD54 upregulation with the second and third treatments were indicative of a prime boost effect in both arms,” Dr. Small stated. “Similarly, the TNC profile over time was similar for both arms.”

Overall incidence of adverse events (AEs) was 81% in the concurrent arm and 77% in the sequential arm. Commonly observed AEs (all grades) included muscle spasms (31% vs. 23%, respectively), oral paresthesia (19% vs. 31%), chills (31% vs. 8%), and cough (19% vs. 15%).

The 2013 Genitourinary Cancers Symposium is co-sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO).


Clinicaltrials.gov ID: NCT01487863