Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer

Roberto Pili, Michael Hag̈gman, Walter M. Stadler, Jeffrey R. Gingrich, Vasileios J. Assikis, Anders Bjor̈k, Or̈jan Nordle, Goran Forsberg, Michael A. Carducci, Andrew J. Armstrong

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

Purpose: The activity of the novel antitumor agent tasquinimod (TASQ) with S100A9 as a molecular target was investigated in men with metastatic castration-resistant prostate cancer (CRPC) and minimal symptoms. Patients and Methods: We conducted a randomized, double-blind, placebo-controlled phase II trial in men assigned (at a ratio of two to one) to either oral once-daily TASQ 0.25 mg/d escalating to 1.0 mg/d over 4 weeks or placebo. The primary end point was the proportion of patients without disease progression at 6 months, defined by Response Evaluation Criteria in Solid Tumors Group, Prostate Cancer Working Group (PCWG2), or pain criteria, excluding prostate-specific antigen. Results: Two hundred one men (134 assigned to TASQ; 67 to placebo) were evaluable, and baseline characteristics were well balanced. Six-month progression-free proportions for TASQ and placebo groups were 69% and 37%, respectively (P < .001), and median progression-free survival (PFS) was 7.6 versus 3.3 months (P =.0042). In PCWG2 CRPC clinical subgroups, PFS in months was as follows: nodal metastases, 6.1 versus 3.1; bone metastases, 8.8 versus 3.4; and visceral metastases, 6.0 versus 3.0 for patients receiving TASQ versus placebo, respectively. Bone alkaline phosphatase levels were stabilized in the TASQ group, whereas the impact on PSA kinetics was less pronounced. Adverse events (AEs) occurring more frequently in the TASQ arm included GI disorders, fatigue, musculoskeletal pains, and elevations of pancreatic and inflammatory biomarkers. Grade 3 to 4 AEs, including asymptomatic elevations of laboratory parameters, were reported in 40% of patients receiving TASQ versus 10% receiving placebo; deep vein thrombosis (4% v 0%) was more common in the TASQ arm. Conclusion: TASQ significantly slowed progression and improved PFS in patients with metastatic CRPC with an acceptable AE profile.

Original languageEnglish (US)
Pages (from-to)4022-4028
Number of pages7
JournalJournal of Clinical Oncology
Volume29
Issue number30
DOIs
StatePublished - Oct 20 2011
Externally publishedYes

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Prostatic Neoplasms
Placebos
Castration
Disease-Free Survival
Neoplasm Metastasis
tasquinimod
Bone and Bones
Musculoskeletal Pain
Prostate-Specific Antigen
Venous Thrombosis
Antineoplastic Agents
Fatigue
Alkaline Phosphatase
Disease Progression
Biomarkers
Pain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer. / Pili, Roberto; Hag̈gman, Michael; Stadler, Walter M.; Gingrich, Jeffrey R.; Assikis, Vasileios J.; Bjor̈k, Anders; Nordle, Or̈jan; Forsberg, Goran; Carducci, Michael A.; Armstrong, Andrew J.

In: Journal of Clinical Oncology, Vol. 29, No. 30, 20.10.2011, p. 4022-4028.

Research output: Contribution to journalArticle

Pili, R, Hag̈gman, M, Stadler, WM, Gingrich, JR, Assikis, VJ, Bjor̈k, A, Nordle, O, Forsberg, G, Carducci, MA & Armstrong, AJ 2011, 'Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer', Journal of Clinical Oncology, vol. 29, no. 30, pp. 4022-4028. https://doi.org/10.1200/JCO.2011.35.6295
Pili, Roberto ; Hag̈gman, Michael ; Stadler, Walter M. ; Gingrich, Jeffrey R. ; Assikis, Vasileios J. ; Bjor̈k, Anders ; Nordle, Or̈jan ; Forsberg, Goran ; Carducci, Michael A. ; Armstrong, Andrew J. / Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 30. pp. 4022-4028.
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abstract = "Purpose: The activity of the novel antitumor agent tasquinimod (TASQ) with S100A9 as a molecular target was investigated in men with metastatic castration-resistant prostate cancer (CRPC) and minimal symptoms. Patients and Methods: We conducted a randomized, double-blind, placebo-controlled phase II trial in men assigned (at a ratio of two to one) to either oral once-daily TASQ 0.25 mg/d escalating to 1.0 mg/d over 4 weeks or placebo. The primary end point was the proportion of patients without disease progression at 6 months, defined by Response Evaluation Criteria in Solid Tumors Group, Prostate Cancer Working Group (PCWG2), or pain criteria, excluding prostate-specific antigen. Results: Two hundred one men (134 assigned to TASQ; 67 to placebo) were evaluable, and baseline characteristics were well balanced. Six-month progression-free proportions for TASQ and placebo groups were 69{\%} and 37{\%}, respectively (P < .001), and median progression-free survival (PFS) was 7.6 versus 3.3 months (P =.0042). In PCWG2 CRPC clinical subgroups, PFS in months was as follows: nodal metastases, 6.1 versus 3.1; bone metastases, 8.8 versus 3.4; and visceral metastases, 6.0 versus 3.0 for patients receiving TASQ versus placebo, respectively. Bone alkaline phosphatase levels were stabilized in the TASQ group, whereas the impact on PSA kinetics was less pronounced. Adverse events (AEs) occurring more frequently in the TASQ arm included GI disorders, fatigue, musculoskeletal pains, and elevations of pancreatic and inflammatory biomarkers. Grade 3 to 4 AEs, including asymptomatic elevations of laboratory parameters, were reported in 40{\%} of patients receiving TASQ versus 10{\%} receiving placebo; deep vein thrombosis (4{\%} v 0{\%}) was more common in the TASQ arm. Conclusion: TASQ significantly slowed progression and improved PFS in patients with metastatic CRPC with an acceptable AE profile.",
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AU - Stadler, Walter M.

AU - Gingrich, Jeffrey R.

AU - Assikis, Vasileios J.

AU - Bjor̈k, Anders

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AU - Forsberg, Goran

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AU - Armstrong, Andrew J.

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