Dose optimisation to improve access to effective cancer medicines

Abstract

Access to many cancer medicines on WHO's Essential Medicines List (EML) is restricted because of price, especially in low-income and middle-income countries (LMICs). Other cancer medicines that have been shown to improve survival, such as immune checkpoint inhibitors for lung cancer, are not included on the EML because approved doses and schedules exceed affordable prices in LMICs. Multiple strategies are therefore needed to reduce medicine costs or circumvent these problems, such as optimising doses and schedules. Cancer medicines are approved by regulatory agencies, such as the US Food and Drug Administration and the European Medicines Agency, following rigorous clinical trials. However, these approvals can involve dosing regimens and treatment schedules that, although effective in showing statistically significant benefits in trials, can be higher in intensity, frequency, or duration than is necessary to achieve meaningful improved survival. In clinical practice, these regimens can lead to concerns about balancing optimal therapeutic outcomes with the risk of side-effects, patient quality of life, and long-term health effects. Various types of evidence can, and should, be used to explore and show near-equivalence of beneficial outcomes from reduced-intensity treatments, including randomised clinical trials, dose-finding phase 1 and 2 studies, and pharmacokinetic and pharmacodynamic studies. The positive effects of proving that lower doses or less intensive schedules retain therapeutic activity include reduced toxicity and large price reductions, leading to better cost-effectiveness and greater access to treatments that improve survival. Beyond regulatory approvals, identification of regimens that have similar outcomes with reduced doses and less intense schedules should be a priority for clinicians and policy makers in the selection process to identify effective medicines at national and global levels.