Hall of Mirrors
Individual Optimal Dosing of Osimertinib and Selumetinib in EGFRm NSCLC Patients (304982)
*Kamrine Poels, Harvard UniversityShaon Chakrabarti, Dana Farber Cancer Institute
Franziska Michor, Harvard University
Keywords: optimal dosing, NSCLC, cancer evolution, pharmacokinetics
Establishing an optimal drug administration schedule is a critical procedure in the treatment of cancer. Furthermore, combination therapy is routinely used due to the rise of resistant mechanisms, and this increases the number of possible dosing schedules. Hence, in-silico clinical trials are an inexpensive method to find an optimal drug regimen. Here, we incorporate data on drug kinetics in serum (pharmacokinetics, PK) with an evolutionary dynamics model based on branching processes, to predict cancer growth under specific dosing regimens. We applied our approach to a clinical trial (TATTON) administering osimertinib and selumetinib to EGFR-m lung cancer patients. We simulated tumor growth of patients under trial arms used in TATTON and under other proposed schedules, and compared all results. We observed significant improvements, with very few subjects performing worse under the recommended schedules. We propose that researchers can individually optimize schedules by obtaining the clinical data and PK parameters of each patient after a week under a traditional schedule, and then change drug administration by selecting the most promising regimen based on our model’s predictions.