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Clin Cancer Res. 2013 Dec 15;19(24):6891-901. doi: 10.1158/1078-0432.CCR-13-1581. Epub 2013 Nov 19.

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

Author information

  • 1Authors' Affiliations: Duke Cancer Institute and the Duke Prostate Center, Duke University, Durham, North Carolina; University Hospital of Uppsala, Uppsala, Sweden; University of Chicago, Chicago, Illinois; University of Pittsburgh, Pittsburgh, Pennsylvania; Peachtree Hematology Oncology Consultants, Atlanta, Georgia; Kaiser Permanente Medical Group, San Diego, California; Sahlgrenska University Hospital, Gothenburg, Sweden; Urologic Consultants of SE PA, Bala Cynwyd, Pennsylvania; Active Biotech AB, Lund, Sweden; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore Maryland; Roswell Park Cancer Institute, Buffalo, New York.

Abstract

PURPOSE:

Tasquinimod (Active Biotech) is an oral immunomodulatory, anti-angiogenic, and anti-metastatic 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 with mCRPC were 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-to-symptomatic 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 of men with minimally symptomatic mCRPC suggests that the prolongation in PFS with tasquinimod may lead to a survival advantage in this setting, particularly among men with skeletal metastases, and has a favorable risk:benefit ratio.

©2013 AACR.

PMID:
24255071
[PubMed - in process]
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