Dosing immune-checkpoint inhibitors: Opportunities for the future

Abstract

With recent breakthroughs in immunotherapy, particularly with the approval of immune checkpoint inhibitors for various cancer indications, patients now have a wider array of treatment options, even for those with metastatic disease. Still, the survival benefit of immune-checkpoint inhibitors is modest, and there is concern about drug toxicity. In addition, there is ongoing exploration into combination therapy involving immune-checkpoint inhibitors, which come at the risk of increased toxicity. Unfortunately, due to the cost of the currently approved doses and dosing intervals, many patients in the community in the United States and low- and middle-income countries lack access to these transformative therapies. Further, the observation of resistance to immune-checkpoint inhibitors and limitations of currently approved doses and dosing intervals warrants changes in current practice. This review paper discusses both model-based and clinical studies in the current literature. Strategies for improving access to immune-checkpoint inhibitors and expanding their utilization, including weight-based dosing instead of fixed dosing, dose and dose interval adjustments, development of biomarkers and scoring systems for personalization of immune-checkpoint inhibitors, and alternative trial design, are discussed.