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.2017-04-122017-04-122016-08-01Sternberg, C., Armstrong, A., Pili, R., Ng, S., Huddart, R., Agarwal, N., ... & Delva, R. (2016). Randomized, double-blind, placebo-controlled phase III study of tasquinimod in men with metastatic castration-resistant prostate cancer. Journal of Clinical Oncology, 34(22), 2636-2643. http://doi.org/10.1200/JCO.2016.66.96971527-7755https://hdl.handle.net/1805/12252PURPOSE: 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.en-USPublisher PolicyTasquinimodmetastatic castration-resistant prostate cancermCRPCArticle