Browsing by Subject "Tasquinimod"

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    Randomized, Double-Blind, Placebo-Controlled Phase III Study of Tasquinimod in Men With Metastatic Castration-Resistant Prostate Cancer
    (American Society of Clinical Oncology, 2016-08-01) Sternberg C.; Armstrong A.; Pili R.; Ng S.; Huddart R.; Agarwal N.; Khvorostenko D.; Lyulko O.; Brize A.; Vogelzang N.; Delva R.; Harza M.; Thanos A.; James N.; Werbrouck P.; Bögemann M.; Hutson T.; Milecki P.; Chowdhury S.; Gallardo E.; Schwartsmann G.; Pouget J.-C.; Baton F.; Nederman T.; Tuvesson H.; Carducci M.; Department of Medicine, IU School of Medicine
    PURPOSE: Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. PATIENTS AND METHODS: Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. RESULTS: In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. CONCLUSION: In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.
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    Tasquinimod targets suppressive myeloid cells in the tumor microenvironment
    (Taylor & Francis, 2018-05-07) Shen, Li; Pili, Roberto; Medicine, School of Medicine
    Infiltrating myeloid derived suppressor cells and tumor-associated macrophages (TAMs) are important components of the immunosuppressive tumor microenvironment. We recently reported that tasquinimod, which binds to S100A9, impairs both infiltration and function of these cells. Here we discuss the underlying mechanisms responsible for targeting multiple suppressive populations and the modulation of the tumor microenvironment.