Translation of Progression-Free Survival Benefit Into Overall Survival in Cancer Trials

• Activity Number: 473
• Type: Contributed
• Date/Time: Wednesday, August 1, 2012 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Yiyun Tang*+ and Keiji Imai and Paul Bycott
• Companies: Pfizer Inc. and Pfizer Inc. and Pfizer Inc.
• Keywords: Oncology ; Clinical Trial ; Survival/Time Post Progression ; Progression Free Survival ; Permutation Test ; Marginal Structural Model

Abstract

Overall survival (OS) has been the gold standard for demonstrating clinical benefit for cancer drugs. Increased acceptance of PFS improvement based on well designed and conducted studies as direct evidence of clinical benefit will accelerate drug development and benefit cancer patients.

As survival post progression (SPP) depends on the total effect of natural disease development, residual effect from experimental treatment and effect from crossover or other subsequent therapies, investigating translation of PFS benefit into OS benefit poses some unique challenges.

We present various methods and analyses to evaluate the impact of 1) natural disease development (e.g. simulations of SPP under different scenarios in the context of a specific advanced oncology disease); 2) subsequent therapy /crossover (e.g. marginal structural modeling using inverse probability of censoring weight, permutation approaches based on observed data) on OS. The implementations to a cancer trial are shown to illustrate these different methods to assess translation of PFS benefit into OS.