Randomized, Double-Blind, Placebo-Controlled Phase III Study of Tasquinimod in Men With Metastatic Castration-Resistant Prostate Cancer.

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.

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.

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.

In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 Jun 13 [Epub]

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, Gilberto Schwartsmann, Jean-Christophe Pouget, Frédérique Baton, Thore Nederman, Helen Tuvesson, Michael Carducci

Cora Sternberg, San Camillo Forlanini Hospitals, Rome, Italy; Andrew Armstrong, Duke Cancer Institute, Duke University, Durham, NC; Roberto Pili, Indiana University School of Medicine, Indianapolis, IN; Siobhan Ng, St John of God Medical Centre, Subiaco, Western Australia, Australia; Robert Huddart, Royal Marsden Hospital, Sutton; Nicholas James, Queen Elizabeth Hospital, Birmingham; Simon Chowdhury, Guy's Hospital and Sarah Cannon Research UK, London, United Kingdom; Neeraj Agarwal, University of Utah, Salt Lake City, UT; Denis Khvorostenko, Leningrad Regional Oncology Dispensary, St Petersburg, Russia; Olexiy Lyulko, Zaporizhzhya Regional Clinical Hospital, Zaporizhzhya, Ukraine; Arija Brize, Riga Eastern Clinical University Hospital, Riga, Latvia; Nicholas Vogelzang, Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Rémy Delva, Centre Régional de Lutte Contre le Cancer Paul Papin, Angers; Jean-Christophe Pouget and Frédérique Baton, Ipsen Innovation, Les Ulis, France; Mihai Harza, Fundeni Clinical Institute, Bucharest, Romania; Anastasios Thanos, Agios Savas Anticancer Oncology Hospital of Athens, Athens, Greece; Patrick Werbrouck, Algemeen Ziekenhuis Groeninge, Kortrijk, Belgium; Martin Bögemann, Universitätsklinikum Münster, Münster, Germany; Thomas Hutson, Texas Oncology, Dallas, TX; Piotr Milecki, Poznan University of Medical Sciences, Poznan, Poland; Enrique Gallardo, Corporació Sanitaria Parc Taulí, Sabadell, Spain; Gilberto Schwartsmann, Hospital De Clinicas De Porto Alegre, Porto Alegre, Brazil; Thore Nederman and Helen Tuvesson, Active Biotech, Lund, Sweden; and Michael Carducci, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD., Cora Sternberg, San Camillo Forlanini Hospitals, Rome, Italy; Andrew Armstrong, Duke Cancer Institute, Duke University, Durham, NC; Roberto Pili, Indiana University School of Medicine, Indianapolis, IN; Siobhan Ng, St John of God Medical Centre, Subiaco, Western Australia, Australia; Robert Huddart, Royal Marsden Hospital, Sutton; Nicholas James, Queen Elizabeth Hospital, Birmingham; Simon Chowdhury, Guy's Hospital and Sarah Cannon Research UK, London, United Kingdom; Neeraj Agarwal, University of Utah, Salt Lake City, UT; Denis Khvorostenko, Leningrad Regional Oncology Dispensary, St Petersburg, Russia; Olexiy Lyulko, Zaporizhzhya Regional Clinical Hospital, Zaporizhzhya, Ukraine; Arija Brize, Riga Eastern Clinical University Hospital, Riga, Latvia; Nicholas Vogelzang, Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Rémy Delva, Centre Régional de Lutte Contre le Cancer Paul Papin, Angers; Jean-Christophe Pouget and Frédérique Baton, Ipsen Innovation, Les Ulis, France; Mihai Harza, Fundeni Clinical Institute, Bucharest, Romania; Anastasios Thanos, Agios Savas Anticancer Oncology Hospital of Athens, Athens, Greece; Patrick Werbrouck, Algemeen Ziekenhuis Groeninge, Kortrijk, Belgium; Martin Bögemann, Universitätsklinikum Münster, Münster, Germany; Thomas Hutson, Texas Oncology, Dallas, TX; Piotr Milecki, Poznan University of Medical Sciences, Poznan, Poland; Enrique Gallardo, Corporació Sanitaria Parc Taulí, Sabadell, Spain; Gilberto Schwartsmann, Hospital De Clinicas De Porto Alegre, Porto Alegre, Brazil; Thore Nederman and Helen Tuvesson, Active Biotech, Lund, Sweden; and Michael Carducci, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD. .

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