Effect of Tumor Size Change and Duration of Response on Overall Survival in Immunotherapy Trials

• Activity Number: 193 - Modeling, Design Strategies and Assessments of Biomarkers
• Type: Contributed
• Date/Time: Tuesday, August 4, 2020 : 10:00 AM to 2:00 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Meihua Wang* and Jing Yang and Iris Wu and Heng Zhou and Cong Chen
• Companies: Merck & Co. and Merck & Co. and Merck and Merck and Merck and Company, Inc.
• Keywords: tumor size reduction; objective response; duration of response; immunotherapy trials

Abstract

Response Evaluation Criteria in Solid Tumors (RECIST) is the primary tool for assessing tumor response in patients with solid tumors. Immunotherapies have shown some unusual response and progression kinetics, such as durable response, “pseudo” progression, and/or delayed response. While it is known that tumor size reduction, objective response and duration of response are predictors of overall survival (OS), very few analyses are available to quantify the contribution of these intermediate endpoints to OS. The quantification of the contribution to OS may help the choice of early efficacy metrics for decision making from compound development perspective. Based on several randomized immunotherapy studies, we assessed the contribution of these intermediate endpoints to OS using proportion of treatment explained (PTE). Various modeling approaches (e.g., fixed timepoint, time-varying) are explored, as well as the confidence intervals of PTE. The features and limitations of each approach will be described.