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

• Published in: European urology Vol. 65; no. 3; pp. 516 - 520
• Main Authors: Wiechno, Paweł, Somer, Bradley G, Mellado, Begoña, Chłosta, Piotr L, Cervera Grau, José Manuel, Castellano, Daniel, Reuter, Christoph, Stöckle, Michael, Kamradt, Jörn, Pikiel, Joanna, Durán, Ignacio, Wedel, Steffen, Callies, Sophie, André, Valérie, Hurt, Karla, Brown, Jacqueline, Lahn, Michael, Heinrich, Bernhard
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.03.2014; Elsevier
• Subjects: Antineoplastic Agents - administration & dosage; Antisense oligonucleotide; Biological and medical sciences; Castration-resistant prostate cancer; Disease-Free Survival; Docetaxel; Drug Therapy, Combination; Gynecology. Andrology. Obstetrics; Humans; LY2181308; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; Oligonucleotides - administration & dosage; Prednisone - administration & dosage; Prostatic Neoplasms, Castration-Resistant - drug therapy; Survivin; Taxoids - administration & dosage; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urology; Castration-resistant prostate cancer; Survivin; Antisense oligonucleotide; LY2181308; Docetaxel; Antineoplastic agent; Nephrology; Prostate disease; Urology; Randomization; Castration; Taxane derivatives; Phase II trial; Antimitotic; Male genital diseases; Human; Corticosteroid; Urinary system disease; Antiinflammatory agent; Prednisone; Malignant tumor; First line treatment; Resistance; Apoptosis inhibitory protein; Sodium; Adrenal hormone; Immunosuppressive agent; Prostate cancer; Cancer
• ISSN: 0302-2838; 1873-7560
• 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.