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Long-term Survival ...
Long-term Survival and Biomarker Correlates of Tasquinimod Efficacy in a Multicenter Randomized Study of Men with Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer.
- Article/chapterEnglish2013
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LIBRIS-ID:oai:DiVA.org:uu-216769
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-216769URI
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https://doi.org/10.1158/1078-0432.CCR-13-1581DOI
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Language:English
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Summary in:English
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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.
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Häggman, MichaelUppsala universitet,Urologkirurgi(Swepub:uu)michhagg
(author)
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Stadler, W M
(author)
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Gingrich, J R
(author)
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Assikis, V
(author)
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Polikoff, J
(author)
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Damber, J E
(author)
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Belkoff, L
(author)
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Nordle, O
(author)
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Forsberg, G
(author)
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Carducci, M A
(author)
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Pili, R
(author)
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Uppsala universitetUrologkirurgi
(creator_code:org_t)
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In:Clinical Cancer Research19:24, s. 6891-69011078-04321557-3265
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Armstrong, A J
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Häggman, Michael
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Stadler, W M
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Gingrich, J R
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Assikis, V
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Polikoff, J
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Damber, J E
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Belkoff, L
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Nordle, O
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Forsberg, G
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Carducci, M A
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Pili, R
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Clinical Cancer ...
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Uppsala University