ORLANDO, FL, USA (UroToday.com) - Our understanding of immunotherapies for prostate cancer (PSA-TRICOM, sipuleucel-T, ipilimumab) is still incomplete as these therapies have demonstrated improved overall survival (OS) without changes in time to progression (TTP) in randomized clinical trials.
In an attempt to better understand this discrepancy, data from studies of PSA-TRICOM was evaluated. PSA-TRICOM is a pox viral vaccine expressing PSA and 3 T-cell co-stimulatory molecules and it has demonstrated PSA-specific immune responses and evidence of clinical activity. This supported the initiation of a phase III trial with PSA-TRICOM, and the trial is currently enrolling patients.
An analysis of NCI PCa trials (including a PSA-TRICOM trial) have suggested that immunotherapies may eventually slow the growth rate (GR) of tumors, leading to unchanged short term TTP, while OS improves (Stein et al. Clin Can Res. 2011).
In a multi-center trial (ECOG 9802), PSA-TRICOM was administered to 50 hormone-naïve patients with non-metastatic, castration-naive PCa, and the patients received treatment every 4 weeks for 3 months, then every 12 weeks (preliminary data previously reported, DiPaola, RS et al. GU Cancers Symposium 2009). PSA values were used to calculate tumor GR within the first 100 days of treatment (no additional therapies were given during this time). The data from these calculations suggest that PSA-TRICOM can significantly alter GR within 3 months. This could explain why immunotherapies have demonstrated improved OS without improved TTP, but it needs to be confirmed in future trials.
A slowing of the GR may not lead to substantial changes in short term TTP, but may improve OS in the long term. An on-going international phase III trial of PSA-TRICOM in minimally symptomatic, metastatic castration-resistant PCa will evaluate this concept.
Presented by James L. Gulley, Ravi Amrit Madan, Wilfred Donald Stein, Julia Wilkerson, William L. Dahut, Christopher Ryan Heery, Jeffrey Schlom, George Wilding, and Robert S. DiPaola at the 2013 Genitourinary Cancers Symposium - February 14 - 16, 2013 - Rosen Shingle Creek - Orlando, Florida USA
Laboratory of Tumor Immunology and Biology, Medical Oncology Branch, National Cancer Institute, Bethesda, MD; Hebrew University, Jerusalem, Israel; Medical Oncology Branch, National Cancer Institute, Bethesda, MD; National Cancer Institute, Bethesda, MD; University of Wisconsin Carbone Cancer Center, Madison, WI; Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ
Written by Anna Forsberg, medical reporter for UroToday.com
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