Randomized, double-blind, placebo-controlled phase III study of tasquinimod in men with metastatic castration-resistant prostate cancer

Cora Sternberg, Andrew Armstrong, Roberto Pili, Siobhan Ng, Robert Huddart, Neeraj Agarwal, Denis Khvorostenko, Olexiy Lyulko, Arija Brize, Nicholas Vogelzang, Rémy Delva, Mihai Harza, Anastasios Thanos, Nicholas James, Patrick Werbrouck, Martin Bögemann, Thomas Hutson, Piotr Milecki, Simon Chowdhury, Enrique Gallardo & 6 others Gilberto Schwartsmann, Jean Christophe Pouget, Frédérique Baton, Thore Nederman, Helen Tuvesson, Michael A Carducci

Research output: Contribution to journalArticle

Abstract

Purpose: Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. Patients and Methods: Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. Results: In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. Conclusion In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

Original languageEnglish (US)
Pages (from-to)2636-2643
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number22
DOIs
StatePublished - Aug 1 2016

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Castration
Prostatic Neoplasms
Placebos
Survival
Disease-Free Survival
Neoplasm Metastasis
Karnofsky Performance Status
Drug Therapy
Bone Neoplasms
Tumor Microenvironment
tasquinimod
Fatigue
Anemia
Age Groups

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Randomized, double-blind, placebo-controlled phase III study of tasquinimod in men with metastatic castration-resistant prostate cancer. / Sternberg, Cora; Armstrong, Andrew; Pili, Roberto; Ng, Siobhan; Huddart, Robert; Agarwal, Neeraj; Khvorostenko, Denis; Lyulko, Olexiy; Brize, Arija; Vogelzang, Nicholas; Delva, Rémy; Harza, Mihai; Thanos, Anastasios; James, Nicholas; Werbrouck, Patrick; Bögemann, Martin; Hutson, Thomas; Milecki, Piotr; Chowdhury, Simon; Gallardo, Enrique; Schwartsmann, Gilberto; Pouget, Jean Christophe; Baton, Frédérique; Nederman, Thore; Tuvesson, Helen; Carducci, Michael A.

In: Journal of Clinical Oncology, Vol. 34, No. 22, 01.08.2016, p. 2636-2643.

Research output: Contribution to journalArticle

Sternberg, C, Armstrong, A, Pili, R, Ng, S, Huddart, R, Agarwal, N, Khvorostenko, D, Lyulko, O, Brize, A, Vogelzang, N, Delva, R, Harza, M, Thanos, A, James, N, Werbrouck, P, Bögemann, M, Hutson, T, Milecki, P, Chowdhury, S, Gallardo, E, Schwartsmann, G, Pouget, JC, Baton, F, Nederman, T, Tuvesson, H & Carducci, MA 2016, 'Randomized, double-blind, placebo-controlled phase III study of tasquinimod in men with metastatic castration-resistant prostate cancer', Journal of Clinical Oncology, vol. 34, no. 22, pp. 2636-2643. https://doi.org/10.1200/JCO.2016.66.9697
Sternberg, Cora ; Armstrong, Andrew ; Pili, Roberto ; Ng, Siobhan ; Huddart, Robert ; Agarwal, Neeraj ; Khvorostenko, Denis ; Lyulko, Olexiy ; Brize, Arija ; Vogelzang, Nicholas ; Delva, Rémy ; Harza, Mihai ; Thanos, Anastasios ; James, Nicholas ; Werbrouck, Patrick ; Bögemann, Martin ; Hutson, Thomas ; Milecki, Piotr ; Chowdhury, Simon ; Gallardo, Enrique ; Schwartsmann, Gilberto ; Pouget, Jean Christophe ; Baton, Frédérique ; Nederman, Thore ; Tuvesson, Helen ; Carducci, Michael A. / Randomized, double-blind, placebo-controlled phase III study of tasquinimod in men with metastatic castration-resistant prostate cancer. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 22. pp. 2636-2643.
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abstract = "Purpose: Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. Patients and Methods: Men with chemotherapy-na{\"i}ve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9{\%} power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80{\%} power to detect a target HR of 0.8 for OS, the key secondary end point. Results: In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥90{\%}, 77.3{\%}; and visceral metastases, 21.1{\%}. Estimated median rPFS by central review was 7.0 months (95{\%} CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95{\%} CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95{\%} CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95{\%} CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95{\%} CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95{\%} CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8{\%} v 33.6{\%}), the most common being anemia, fatigue, and cancer pain. Conclusion In chemotherapy-na{\"i}ve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.",
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TY - JOUR

T1 - Randomized, double-blind, placebo-controlled phase III study of tasquinimod in men with metastatic castration-resistant prostate cancer

AU - Sternberg, Cora

AU - Armstrong, Andrew

AU - Pili, Roberto

AU - Ng, Siobhan

AU - Huddart, Robert

AU - Agarwal, Neeraj

AU - Khvorostenko, Denis

AU - Lyulko, Olexiy

AU - Brize, Arija

AU - Vogelzang, Nicholas

AU - Delva, Rémy

AU - Harza, Mihai

AU - Thanos, Anastasios

AU - James, Nicholas

AU - Werbrouck, Patrick

AU - Bögemann, Martin

AU - Hutson, Thomas

AU - Milecki, Piotr

AU - Chowdhury, Simon

AU - Gallardo, Enrique

AU - Schwartsmann, Gilberto

AU - Pouget, Jean Christophe

AU - Baton, Frédérique

AU - Nederman, Thore

AU - Tuvesson, Helen

AU - Carducci, Michael A

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Purpose: Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. Patients and Methods: Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. Results: In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. Conclusion In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

AB - Purpose: Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. Patients and Methods: Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. Results: In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. Conclusion In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

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