Changes in Tumor Size as a Continuous Variable in Phase II Trials Rather Than WHO/RECIST Response to Improve Success Rate of Confirmatory Phase III Trials

• Activity Number: 515
• Type: Contributed
• Date/Time: Wednesday, August 1, 2012 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Zhengjia Chen*+ and Sungjin Kim and Taofeek K Owonikoko and Zhibo Wang and Suresh S Ramalingam and Dong M Shin and Fadlo R Khuri and Jeanne Kowalski
• Companies: Biostatistics and Bioinformatics Shared Resource at Winship Cancer Institute and Winship Cancer Institute and Emory University and Winship Cancer Institute and Emory University and Emory University and Emory University and Biostatistics and Bioinformatics Shared Resource at Winship Cancer Institute
• Keywords: Tumor response ; World Health Organization (WHO) ; and Response Evaluation Criteria In Solid Tumors (RECIST) ; Percent tumor change ; Efficacy ; Success rate of Phase III trials

Abstract

In Phase II cancer clinical trials, tumor response is widely used as a surrogate for clinical benefit and overall survival. The change in tumor size, a continuous variable, is typically transformed into a categorical variable (complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)) according to two well-established and widely employed criteria: WHO and RECIST. It is generally assumed that patient's survival chance increases with the magnitude of tumor response i.e. CR>PR>SD>PD. But from statistical consideration, this approach results in loss of study power by not fully utilizing all available data. We employed survival as a gold standard to compare the powers to accurately establish treatment efficacy between two approaches: a continuous endpoint (tumor percent change) and its categorical endpoint (tumor response according to WHO/RECIST). Simulation studies and real data from a completed Phase II trial show that the continuous endpoint achieved a higher power to identify a treatment agent likely to achieve significantly improved survival, thus resulting in substantial improvement in trial efficiency and success rate of Phase III clinical trial