Case Study on Interpretation of Progression-Free Survival and Overall Survival in a Trial with Treatment Crossover: Tivozanib in Renal Cancer

• Activity Number: 282
• Type: Topic Contributed
• Date/Time: Tuesday, August 5, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biometrics Section
• Author(s): Andrew Strahs*+
• Companies: Alnylam Pharmaceuticals
• Keywords: progression-free survival ; overall survival ; cancer ; RPSFT ; IPCW ; survival analysis

Abstract

We discuss the experience of tivozanib in renal cancer as a case study on the interpretation of progression free survival and overall survival. Tivozanib is a tyrosine kinase inhibitor of VEGF. The TIVO-1 trial compared tivozanib against an active control, sorafenib. TIVO-1 enrolled the majority of its 517 patients in Eastern Europe. The primary endpoint was progression-free survival (PFS); overall survival (OS) was a secondary endpoint. Patients whose cancer progressed on sorafenib were offered the opportunity to cross over to receive tivozanib; this option was widely utilized. Ultimately, PFS favored tivozanib (HR=0.80, p=0.042) but OS trended longer in the control arm (HR=1.25, p=0.10). These results were discussed at the US FDA's Oncology Drugs Advisory Committee on May 2, 2013.