A randomised phase 2 study combining LY2181308 sodium (survivin antisense oligonucleotide) with first-line docetaxel/prednisone in patients with castration-resistant prostate cancer.
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.
Uro-Oncology Department, Cancer Center, Warsaw, Poland. Electronic address: wiechno@coi.waw.pl.
Paweł
P
Wiechno
West Clinic and ACORN, Memphis, TN, USA.
Bradley G
BG
Somer
Medical Oncology Department, Hospital Clínic, University of Barcelona, Barcelona, Spain.
Begoña
B
Mellado
Department of Urology, Jagiellonian University in Krakow, Krakow, Poland.
Piotr L
PL
Chłosta
Benidorm Clinic Hospital, Benidorm, Spain.
José Manuel
JM
Cervera Grau
Medical Oncology Service, 12 de Octubre University Hospital, Madrid, Spain.
Daniel
D
Castellano
Department of Haematology, Haemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Christoph
C
Reuter
Clinic for Urology and Paediatric Urology, University of Saarland, Saarland, Germany.
Michael
M
Stöckle
Clinic for Urology and Paediatric Urology, University of Saarland, Saarland, Germany.
Jörn
J
Kamradt
Wojewódzkie Cancer Centre, Gdansk, Poland.
Joanna
J
Pikiel
Centro Integral Oncológico Clara Campal, Madrid, Spain.
Ignacio
I
Durán
Department of Urology, Goethe-University, Frankfurt am Main, Germany.
Steffen
S
Wedel
Global Pharmacokinetics/Pharmacodynamics Department, Eli Lilly and Company, Erl Wood, UK.
Sophie
S
Callies
Global Statistical Sciences, Eli Lilly and Company, Erl Wood, UK.
Valérie
V
André
Division of Early Phase Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA.
Karla
K
Hurt
Global Health Outcomes, Eli Lilly and Company, Erl Wood, UK.
Jacqueline
J
Brown
Division of Early Phase Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA.
Michael
M
Lahn
Haematological-Oncological Practice Brudler/Heinrich/Bangerter, Augsburg, Germany.
Bernhard
B
Heinrich
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D009841:Oligonucleotides / Q000008:administration & dosage*; D011241:Prednisone / Q000008:administration & dosage*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage*
D000970:Antineoplastic Agents; C529350:LY 2181308; D009841:Oligonucleotides; D043823:Taxoids; D000077143:Docetaxel; D011241:Prednisone
Antisense oligonucleotide; Castration-resistant prostate cancer; Docetaxel; LY2181308; Survivin