Author: Mark Dresser, PhD on March 23, 2018 .png)
In a recent Review published in Clinical and Translational Science (CTS), Ji and colleagues provide an excellent summary of the recent progress and future opportunities, as well as challenges in determining the optimal dose for oncology and immuno-oncology therapeutics. While the approaches to dose finding are well established for many therapeutic areas, this remains a very active area of research in oncology for a number of reasons. On the one hand, there are historical, logistical, and data-related limitations and constraints in oncology clinical studies. For example, continued widespread use of the maximum tolerated dose (MTD) approach to dose finding in small numbers of patients often yields single agent dose escalation data for therapeutics that will be used in combination and whose mechanism of action suggests that the MTD paradigm may not be the most relevant. Furthermore, in later stage clinical testing, it remains a rare exception to study more than one dose in pivotal oncology clinical studies, resulting in limited datasets to characterize and elucidate dose-exposure-response relationships.
On the other hand, despite these limitations and challenges, there are a number of reasons to be optimistic for continued and significant future progress. For example, a wide range of endpoints are now routinely incorporated into oncology clinical trials ranging from target engagement and disease-relevant biomarkers, response endpoints, and safety endpoints. Applying modeling and simulation approaches to these types of datasets has resulted in key insights to the dose finding question for many oncology therapeutics. In their review Ji and colleagues provide a number of compelling recent technical successes and also highlight excellent industry-academic-government collaborations, which have been instrumental to advancements in dose finding in oncology. CTS has recently published original research articles in the area of dose finding in oncology, such as this paper by Rudek et al., and the Editorial Team encourages more submissions on this topic.
Image by Ji, et al. Clin. Trans. Sci., doi: 10.1111/cts.12540, is licensed under CC BY-NC 4.0. ©2018 The authors.
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