Modifying Adaptive Therapy to Enhance Competitive Suppression

SIMPLE SUMMARY: Adaptive therapy is a new approach to cancer treatment that aims to forestall treatment resistance by controlling instead of minimizing tumor burdens. The underlying hypothesis is that drug-sensitive cancer cells can competitively suppress drug-resistant cells and greatly increase the amount of time that a therapy is effective. This approach is being tested in a clinical trial, and the preliminary results are extremely promising. If these promising results can indeed be attributed to the competitive suppression of resistance, then identifying simple ways to enhance competitive suppression should increase the benefits of this therapy. Here, we show that simple modifications to the design of adaptive therapy should greatly enhance its performance and also increase the range of patients who can benefit from it. Importantly, this investigation also highlights key assumptions underlying the design of adaptive therapy and emphasizes that these must be validated if adaptive therapy is to be optimized and used effectively. ABSTRACT: Adaptive therapy is a promising new approach to cancer treatment. It is designed to leverage competition between drug-sensitive and drug-resistant cells in order to suppress resistance and maintain tumor control for longer. Prompted by encouraging results from a recent pilot clinical trial, we evaluate the design of this initial test of adaptive therapy and identify three simple modifications that should improve performance. These modifications are designed to increase competition and are easy to implement. Using the mathematical model that supported the recent adaptive therapy trial, we show that the suggested modifications further delay time to tumor progression and also increase the range of patients who can benefit from adaptive therapy.