Section: New Results

Optimal Scheduling of Bevacizumab and Pemetrexed/cisplatin Dosing in Non‐Small Cell Lung Cancer

Authors: Benjamin Schneider, Arnaud Boyer, Joseph Ciccolini, Fabrice Barlési, Kenneth Wang, Sébastien Benzekry${}^{*}$, Jonathan Mochel${}^{*}$. ${}^{*}$ = co-senior authors. Published in CPT: Pharmacometrics and Systems Pharmacology. https://hal.inria.fr/hal-02109335

Bevacizumab-pemetrexed/cisplatin (BEV-PEM/CIS) is a first line therapeutic for advanced non-squamous non-small cell lung cancer (NSCLC). Bevacizumab potentiates PEM/CIS cytotoxicity by inducing transient tumor vasculature normalization. BE V- PEM/CIS has a narrow therapeutic window. Therefore, it is an attractive target for administration schedule optimization. The present study leverages our previous work on BEV-PEM/CIS pharmacodynamic modeling in NSCLC-bearing mice to estimate the optimal gap in the scheduling of sequential BEV-PEM/CIS. We predicted the optimal gap in BEV-PEM/CIS dosing to be 2.0 days in mice and 1.2 days in humans. Our simulationssuggest that the efficacy loss in scheduling BEV-PEM/CIS at too great of a gap is much less than the efficacy loss in scheduling BEV-PEM/CIS at too short of a gap.