2. Academic Validation
  3. A randomised phase 2 study combining LY2181308 sodium (survivin antisense oligonucleotide) with first-line docetaxel/prednisone in patients with castration-resistant prostate cancer

A randomised phase 2 study combining LY2181308 sodium (survivin antisense oligonucleotide) with first-line docetaxel/prednisone in patients with castration-resistant prostate cancer

  • Eur Urol. 2014 Mar;65(3):516-20. doi: 10.1016/j.eururo.2013.10.039.
Paweł Wiechno 1,  Bradley G Somer 2,  Begoña Mellado 3,  Piotr L Chłosta 4,  José Manuel Cervera Grau 5,  Daniel Castellano 6,  Christoph Reuter 7,  Michael Stöckle 8,  Jörn Kamradt 8,  Joanna Pikiel 9,  Ignacio Durán 10,  Steffen Wedel 11,  Sophie Callies 12,  Valérie André 13,  Karla Hurt 14,  Jacqueline Brown 15,  Michael Lahn 14,  Bernhard Heinrich 16
Affiliations

Affiliations

  • 1 Uro-Oncology Department, Cancer Center, Warsaw, Poland. Electronic address: wiechno@coi.waw.pl.
  • 2 West Clinic and ACORN, Memphis, TN, USA.
  • 3 Medical Oncology Department, Hospital Clínic, University of Barcelona, Barcelona, Spain.
  • 4 Department of Urology, Jagiellonian University in Krakow, Krakow, Poland.
  • 5 Benidorm Clinic Hospital, Benidorm, Spain.
  • 6 Medical Oncology Service, 12 de Octubre University Hospital, Madrid, Spain.
  • 7 Department of Haematology, Haemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
  • 8 Clinic for Urology and Paediatric Urology, University of Saarland, Saarland, Germany.
  • 9 Wojewódzkie Cancer Centre, Gdansk, Poland.
  • 10 Centro Integral Oncológico Clara Campal, Madrid, Spain.
  • 11 Department of Urology, Goethe-University, Frankfurt am Main, Germany.
  • 12 Global Pharmacokinetics/Pharmacodynamics Department, Eli Lilly and Company, Erl Wood, UK.
  • 13 Global Statistical Sciences, Eli Lilly and Company, Erl Wood, UK.
  • 14 Division of Early Phase Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA.
  • 15 Global Health Outcomes, Eli Lilly and Company, Erl Wood, UK.
  • 16 Haematological-Oncological Practice Brudler/Heinrich/Bangerter, Augsburg, Germany.
PMID: 24246407 DOI: 10.1016/j.eururo.2013.10.039
Abstract

Castration-resistant prostate Cancer (CRPC) is partially characterised by overexpression of antiapoptotic proteins, such as Survivin. In this phase 2 study, patients with metastatic CRPC (n=154) were randomly assigned (1:2 ratio) to receive standard first-line docetaxel/prednisone (control arm) or the combination of LY2181308 with docetaxel/prednisone (experimental arm). The primary objective was to estimate progression-free survival (PFS) for LY2181308 plus docetaxel. Secondary efficacy measures included overall survival (OS), several predefined prostate-specific antigen (PSA)-derived end points, and Brief Pain Inventory (BPI) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores. The median PFS of treated patients for the experimental arm (n=98) was 8.64 mo (90% confidence interval [CI], 7.39-10.45) versus 9.00 mo (90% CI, 7.00-10.09) in the control arm (n=51; p=0.755). The median OS for the experimental arm was 27.04 mo (90% CI, 19.94-33.41) compared with 29.04 mo (90% CI, 20.11-39.26; p=0.838). The PSA responses (≥ 50% PSA reduction), BPI, and FACT-P scores were similar in both arms. In the experimental arm, patients had a numerically higher incidence of grades 3-4 neutropenia, anaemia, thrombocytopenia, and sensory neuropathy. In conclusion, this study failed to detect a difference in efficacy between the two treatment groups.

Keywords

Antisense oligonucleotide; Castration-resistant prostate cancer; Docetaxel; LY2181308; Survivin.

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