Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer

A. J. Armstrong, M. Häggman, W. M. Stadler, J. R. Gingrich, V. Assikis, J. Polikoff, J. E. Damber, L. Belkoff, Ö Nordle, G. Forsberg, M. A. Carducci, R. Pili

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Purpose: Tasquinimod (Active Biotech) is an oral immunomodulatory, anti-angiogenic, and antimetastatic agent that delayed metastatic disease progression in a randomized placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). Here, we report long-term survival with biomarker correlates from this trial. Experimental Design: Two hundred and one (134 tasquinimod and 67 placebo) men withmCRPCwere evaluated. Forty-one men randomized to placebo crossed over to tasquinimod. Survival data were collected with a median follow-up time of 37 months. Exploratory biomarker studies at baseline and over time were collected to evaluate potential mechanism-based correlates with tasquinimod efficacy including progression-free survival (PFS) and overall survival (OS). Results: With 111 mortality events, median OS was 33.4 months for tasquinimod versus 30.4 months for placebo overall, and 34.2 versus 27.1 months in men with bone metastases (n = 136), respectively. Multivariable analysis demonstrated an adjusted HR of 0.52 [95% confidence interval (CI), 0.35-0.78; P = 0.001] for PFS and 0.64 (95% CI, 0.42-0.97; P = 0.034) for OS, favoring tasquinimod. Time-tosymptomatic progression was improved with tasquinimod (P = 0.039, HR = 0.42). Toxicities tended to be mild in nature and improved over time. Biomarker analyses suggested a favorable impact on bone alkaline phosphatase and lactate dehydrogenase (LDH) over time and a transient induction of inflammatory biomarkers, VEGF-A, and thrombospondin-1 levels with tasquinimod. Baseline levels of thrombospondin-1 less than the median were predictive of treatment benefit. Conclusions: The survival observed in this trial ofmen withminimally symptomaticm CRPC suggests that the prolongation in PFS with tasquinimodmay lead to a survival advantage in this setting, particularly among men with skeletalmetastases, and has a favorable risk:benefit ratio.

Original languageEnglish (US)
Pages (from-to)6891-6901
Number of pages11
JournalClinical Cancer Research
Volume19
Issue number24
DOIs
StatePublished - Dec 15 2013
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer'. Together they form a unique fingerprint.

  • Cite this

    Armstrong, A. J., Häggman, M., Stadler, W. M., Gingrich, J. R., Assikis, V., Polikoff, J., Damber, J. E., Belkoff, L., Nordle, Ö., Forsberg, G., Carducci, M. A., & Pili, R. (2013). Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer. Clinical Cancer Research, 19(24), 6891-6901. https://doi.org/10.1158/1078-0432.CCR-13-1581