Figure 4. Survival in a virtual clinical trial utilizing two non-cross resistant therapies.

Approximately 3 million virtual patients were treated with each of these strategies. The x axis shows time (weeks) and the y axis shows surviving patient fraction. Strategy 0 (dark blue) is the current personalized medicine strategy: treatment with the best drug for the observed predominant cell type and switching to the alternative drug on tumor progression or relapse. Strategy 1 (green) minimizes total cell numbers at the next timepoint. Strategy 2.1 (red) minimizes the chance of developing doubly resistant cells at the next timepoint unless the patient has detectable disease (10⁹ cells); in that case, total cell number is minimized. Strategy 2.2 (light blue) minimizes the chance of developing doubly resistant cells at the next timepoint unless the patient has a large disease burden (10¹¹ cells); in that case, total cell number is minimized. Strategy 3 minimizes the total cell population unless the predicted number of doubly resistant cells at the next timepoint is ≥ 1; then the likelihood of formation of doubly resistant cells is minimized. Strategy 4 (olive) predicts the time to mortality (10¹³ cells) and the time to doubly resistant cells, and prioritizes the most imminent threat. Adapted from [67].