US Food and Drug Administration embraces using innovation to identify optimized dosages for patients with cancer

作者：Stacy S. Shord, Hao‐Jie Zhu, Jiang Liu, Atiqur Rahman, Brian Booth, Issam Zineh · 发表于：CPT Pharmacometrics & Systems Pharmacology · 年份：2023 · DOI：10.1002/psp4.13033 · 被引用次数：10 · 研究领域：Statistical Methods in Clinical Trials、Cancer Genomics and Diagnostics、Biosimilars and Bioanalytical Methods

Given evidence that currently used dosing regimens are not tolerable for many patients with cancer, the public has expressed an urgent need to optimize dosages for oncology drugs. Many dose-finding trials (e.g., 3 + 3) are designed to identify the maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs) documented within the first cycle (i.e., 28 days); this paradigm was initially implemented for cytotoxic chemotherapy based on their typically steep dose–response curve and the assumption that higher doses are more efficacious for this fatal disease. This paradigm unfortunately often leads to dosages that are inadequately characterized during development and that result in substantial toxicity. With the emergence of targeted therapies and immunotherapies and improvement in the long-term prognosis for many cancers, we believe that oncology drug development needs to embrace new approaches that consider all available clinical and nonclinical data (not just short-term safety data) in real time. Translational strategies that iteratively evaluate emerging data should be considered to increase the likelihood of identifying dosages that optimize the long-term benefits and maintain the quality of life of all patients with cancer. To that end, we support using innovative approaches that can facilitate the development and application of alternative dose-finding methods either alone or in conjunction with the well-established strategies to the ultimate benefit of patients. Th...