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

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.

Details

Authors
  • 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
  • And 6 others
  • Gilberto Schwartsmann
  • Jean Christophe Pouget
  • Frédérique Baton
  • Thore Nederman
  • Helen Tuvesson
  • Michael Carducci
External organisations
  • Azienda Ospedaliera San Camillo Forlanini
  • Duke University
  • Indiana University
  • St John of God Medical Centre
  • Royal Marsden Hospital
  • University of Utah
  • Leningrad Regional Oncology Dispensary
  • Zaporizhzhya Regional Clinical Hospital
  • Riga Eastern Clinical University Hospital
  • Comprehensive Cancer Centers of Nevada
  • Centre Paul Papin
  • Fundeni Clinical Institute
  • Agios Savvas Anticancer Oncology Hospital of Athens
  • New Queen Elizabeth Hospital
  • Algemeen Ziekenhuis Groeninge
  • Universitätsklinikum Münster
  • Texas Oncology
  • Poznan University of Medical Sciences
  • Guy's and St Thomas' NHS Foundation Trust
  • Hospital Universitari De Sabadell-corporació Parc Taulí
  • Hospital de Clinicas de Porto Alegre
  • IPSEN Foundation
  • Active Biotech Research AB
  • Johns Hopkins University School of Medicine
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)2636-2643
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number22
Publication statusPublished - 2016 Aug 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes