A Randomised Phase 2 Study Combining LY2181308 Sodium (Survivin Antisense Oligonucleotide) with First-line Docetaxel/Prednisone in Patients with Castration-resistant Prostate Cancer

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.