SAN FRANCISCO, CA USA (UroToday.com) - One potential new approach to enhance antitumor immunity in prostate cancer is blockade of the immune checkpoint molecule, cytotoxic T-lymphocyte antigen-4 (CTLA-4).
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Ipilimumab blocks negative signaling of CTLA4 via the Fab portion. CA184-043 was a randomized, double blind, placebo controlled, phase III trial of ipilimumab for treatment of metastatic castration-resistant prostate cancer (mCRPC). The trial was performed among patients already exposed to docetaxel, and patients were randomized in a 1:1 ratio. All patients received a single dose of bone directed radiation therapy (8Gy) prior to initiation of ipilimumab in hopes of releasing tumor antigens to facilitate checkpoint blockade. Patients were pre-stratified by investigator site, alkaline phosphatase (ALP), hemoglobin, and ECOG PS.
While the trial did not reach significance for its primary endpoint of overall survival (OS), evidence of antitumor activity was observed. The authors performed a number of post-hoc subset analyses in an attempt to identify features predictive of response to ipilimumab, the results of which were presented today. Presence of visceral metastases appears to interact with treatment effect (HR 1.644, p0.005; not corrected for multiple comparisons). In patients with more favorable prognostic factors, ipilimumab is associated with improved OS (absence of visceral metastases [median OS 14.4 vs. 10.3 months], ALP < 1.5 [median OS 16.5 vs 12.8 months], and hemoglobin ≥ 11 g/dL [median OS 15.3 vs 12.0 months]). Based on these subset analyses, ipilimumab added to radiation therapy appears to have greater activity than RT alone in patients with a favorable prognostic profile. Patients with mCRPC and favorable features may be more likely to benefit from ipilimumab, and antitumor activity is suggested by other efficacy endpoints (PFS, PSA response rates).
Dr. Drake stressed that these findings were investigational and based on retrospective analyses, and could be used to identify future benchmarks for clinical trials. A phase III trial in chemotherapy-naïve patients is ongoing.
Highlights of a presentation by Charles G. Drake, MD, PhD at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
Johns Hopkins University School of Medicine, Baltimore, MD USA