919P - Tasquinimod mechanism of action biomarkers: correlation with PFS and survival in men with metastatic castrate resistant prostate cancer treated in a...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Prostate Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Michael Carducci
Authors M. Carducci1, A.J. Armstrong2, M. Häggman3, W.M. Stadler4, J.R. Gingrich5, V. Assikis6, G. Forsberg7, A. Olsson8, Ö. Nordle9, R. Pili10
  • 1Oncology, Kimmel Cancer Center, Baltimore/US
  • 2Divisions Of Medical Oncology And Urology, Duke University, Durham/US
  • 3Urology, University Hospital of Uppsala, Uppsala/SE
  • 4Medical Oncology, University of Chicago, Chicago/US
  • 5Urology, University of Pittsburgh, Pittsburgh/US
  • 6Oncology, Peachtree Hematology and Oncology, Atlanta/US
  • 7Active Biotech AB, 22007 - Lund/SE
  • 8Bioscience, Active Biotech, Lund/SE
  • 9Development, Active Biotech, Lund/SE
  • 10Oncology, Roswell Park Medical Centre, Buffalo/US



Tasquinimod (T) is an oral quinoline-3-carboxamide derivative that binds to S100A9 and displays immunomodulatory, anti-angiogenic and anti-metastatic activity. Between Dec 2007 and June 2009, 201 (134 T, 67 Placebo (P)) men with metastatic castrate resistant prostate cancer (CRPC) were randomized and received once-daily treatment with 41 P patients crossing over to T after 6 months or disease progression. The primary endpoint to demonstrate an improvement in PCWG2 criteria-defined progression at 6 months was met (69 vs. 37 % of patients (T/P) were progression free) with PFS of 7.6 vs. 3.3 months (T/P) with acceptable toxicity (Pili, 2011, J Clin Oncol, 20, 4022.). A trend for survival benefit (33.4 vs 30.4 mo) was observed and was most pronounced in the PCWG2 defined subpopulation (92 T, 44 P) with bone metastatic disease (34.2 vs 27.1 mo). This abstract provides exploratory data on biomarkers and therapeutic outcome after Tasquinimod therapy.


The biomarkers PSA, LDH, Bone alkaline phosphatase (BAP), VEGF-A, VEGF-C, thrombospondin-1 (TSP-1), sRAGE and TGF-b were analyzed in serum or plasma before and during therapy in at least the subset of patients with bone metastatic disease. The influence of each (log2 transformed) biomarker on PFS and OS was estimated with Cox Regression (SAS, SAS Institute Inc, Cary, NC).


Eight weeks Tasquinimod treatment was associated with an increase (% vs P) in median circulating levels of VEGF-A (40 %) and TSP-1 (21%) and a decrease in bone alkaline phosphatase (14 %). An increased ratio (week 8/baseline) was associated with more rapid progression and shorter survival for TSP-1 (PFS HR = 1.29, p = 0.052; OS HR = 1.25, p= 0.058), VEGF-C (PFS HR = 1.52, p = 0.060 OS HR = 1.39, p = 0.039) and TGF-b (PFS HR = 1.30, p = 0.091 OS HR = 1.27, p = 0.082). These changes did not correlate with changes in PSA.


PFS and OS observed after Tasquinimod treatment are encouraging. Biomarker analysis supports an effect on both immunomodulation as well as angiogenesis. Changes in the levels of TGF-b, TSP-1 or VEGF-C may be markers for treatment benefit. A controlled phase III study is ongoing in men with bone metastatic CRPC.


M. Carducci: Advisory role Active Biotech, uncompensated,

A. Armstrong: Advisor Active Biotech and Ipsen Research Funding Active Biotech,

M. Häggman: Advisory board Ipsen,

G. Forsberg: Employed by Active Biotech Shareholder in Active Biotech,

A. Olsson: Employed by Active Biotech Share holder Active Biotech,

Ö. Nordle: Employed by Active Biotech Shareholder Active Biotech,

R. Pili: Advisor Active Biotech Research funding Active Biotech,

All other authors have declared no conflicts of interest.