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. 2021 Jun 17;12:3697. doi: 10.1038/s41467-021-23912-4

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© The Author(s) 2021, corrected publication 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a Schematic overview of simulation steps comparison of dosing schedules for one individual. b Distribution of cell types before the initiation of the in silico trial over 1000 simulated patients (rows). c Conventional (top) and proposed (bottom) dose-escalation schedules to identify the MTD in a phase I study. d Comparison in outcomes of different schedules identified by their dacomitinib and osimertinib doses on the axes; the y axis is median improvement percentage of 30 mg QD of dacomitinib and 40 mg BID of osimertinib (proposed level 3 schedule) relative to each dose combination is shown after 1 year of treatment. e, f Waterfall plots with the relative improvement percentage of our proposed schedules compared to the conventional schedules after 8 weeks (2 treatment cycles) and 1 year of treatment, respectively, for 100 patients.