Duration of and time to response in oncology clinical trials from the perspective of the estimand framework

Abstract

Duration of response (DOR) and time to response (TTR) are typically evaluated as secondary endpoints in early‐stage clinical studies in oncology when efficacy is assessed by the best overall response and presented as the overall response rate. Despite common use of DOR and TTR in particular in single‐arm studies, the definition of these endpoints and the questions they are intended to answer remain unclear. Motivated by the estimand framework, we present relevant scientific questions of interest for DOR and TTR and propose corresponding estimand definitions. We elaborate on how to deal with relevant intercurrent events which should follow the same considerations as implemented for the primary response estimand. A case study in mantle cell lymphoma illustrates the implementation of relevant estimands of DOR and TTR. We close the paper with practical recommendations to implement DOR and TTR in clinical study protocols.

Harnessing Immune Checkpoint Inhibitors Against Gastric Cancer: Charting the Course to Expanded Therapeutic Benefit

“…Challenges such as the small cohort size in earlyphase trials like KEYNOTE-059 42 , limited followup durations 43 , the predominance of Asian patient populations in trials [44][45][46] , and the complex landscape of PD-L1 biomarker testing in clinical settings 47,48 , highlight the need for cautious interpretation of these trials' generalizability. Addressing the variability and costs associated with PD-L1 testing remains crucial for integrating ICIs effectively into treatment paradigms 49 .…”