A Phase 3, randomized, double-blind, placebo-controlled study of tasquinimod (TASQ) in men with metastatic castration-resistant prostate cancer (mCRPC), secondary endpoints.

Abstract

239 Background: TASQ is an oral agent with immunomodulatory, anti-angiogenic and anti-metastatic properties that targets the tumor microenvironment. It was recently reported from this study that in chemotherapy-naïve men with mCRPC, single-agent TASQ statistically significantly improved rPFS, by both central (HR (95% CI) 0.64 (0.54-0.75)) and local review, as compared to PBO but no OS benefit was demonstrated (HR (95% CI) 1.10 (0.94-1.28)). In this abstract the results of secondary efficacy endpoint analyses are presented. Methods: Men with asymptomatic to mildly symptomatic chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive TASQ or PBO once daily until progression or toxicity. Randomization was stratified by KPS ( ≥ 90% vs < 90%), presence/absence of visceral disease, and geographic region. The secondary efficacy endpoints discussed here include a panel of radiological, PSA based and symptomatically assessed measures. Results: 1245 pts were randomized (TASQ, n = 832; PBO, n = 413) between 29 Mar 2011 and 7 Dec 2012 at 240 sites in 37 countries. Baseline characteristics were balanced between the 2 groups. In general, all radiology-based and PSA-based secondary endpoints showed statistically significant differences between TASQ and PBO in favor of TASQ. E.g. median time to radiological progression was 8.4 m for TASQ vs. 5.5 m for PBO, p < 0.001, HR (95% CI) 0.628 (0.534-0.739) by central assessment. However, symptomatically assessed endpoints in general showed statistically significant differences in favor of PBO. E.g. median time to symptomatic progression was 9.5 m for TASQ vs. 11.9 m for PBO, p = 0.031, HR (95% CI) 1.171 (1.014-1.353). Grade ≥ 3 TEAEs were more common with TASQ than PBO (42.8 vs 33.6%). Conclusions: Outcome of the radiological and PSA-based endpoints favor TASQ in contrast to the symptomatically assessed endpoints, which favor placebo. Overall survival was not improved, which may be due to limited efficacy of TASQ in the studied population, toxicity, or the differential use of effective life-prolonging agents post-TASQ/placebo. Clinical trial information: NCT01234311.