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

Bevacizumab‐pemetrexed/cisplatin ( BEV ‐ PEM / CIS ) is a first‐line therapeutic for advanced nonsquamous non‐small cell lung cancer. Bevacizumab potentiates PEM / CIS cytotoxicity by inducing transient tumor vasculature normalization. BEV ‐ 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 non‐small cell lung cancer–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 simulations suggest 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.