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
  • 1. Uro-Oncology Department, Cancer Center, Warsaw, Poland. Electronic address: [email protected].
  • 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.
Products