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• W3080851661 abstract "The mutation rate of T790M might change the effective therapeutic sequence of EGFR tyrosine kinase inhibitors (TKIs). This simulation estimates the T790M positivity rate required for first-line first- or second-generation EGFR TKI to exceed overall progression-free survival (PFS) of first-line osimertinib.The PFS of each treatment with EGFR TKIs as first-line treatment, with osimertinib as second-line treatment among T790M-positive cases, and chemotherapy as second-line treatment among T790M-negative cases was set based on phase 3 trials. Overall PFS A of upfront osimertinib and overall PFS B of first- or second-generation EGFR TKIs followed by osimertinib or chemotherapy were simulated at different T790M mutation rates, to estimate the T790M mutation rate at which PFS B exceeds PFS A.Upfront osimertinib: In the setting of PFS of 19 months with first-line osimertinib, the median overall PFS A was 24.8 months (95% confidence interval [CI]: 21.6-28.0 mo). Upfront first- or second-generation EGFR TKI: When the T790M positivity rate was set to 50% and the PFS of second-line osimertinib was 10 months, the total median PFS (PFS B) was 20.2 months (95% CI: 17.5-22.9 mo). Even at a T790M mutation rate of 100%, PFS B (24.7 mo; 95% CI: 21.9-27.9 mo) was shorter than PFS A.Even with a T790M mutation rate of 100%, upfront osimertinib treatment is associated with better median PFS than the upfront treatment with first- or second-generation EGFR TKIs. Consistent with the results of the FLAURA trial, with regard to EGFR TKI monotherapy in the first-line treatment, upfront osimertinib would contribute to good prognosis." @default.
• W3080851661 created "2020-09-01" @default.
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• W3080851661 date "2020-11-01" @default.
• W3080851661 modified "2023-10-16" @default.
• W3080851661 title "Optimizing Sequential Treatment With EGFR Tyrosine Kinase Inhibitor With a Simulation of the T790M Mutation Rate in EGFR–Mutated Lung Cancer" @default.
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• W3080851661 doi "https://doi.org/10.1016/j.jtocrr.2020.100085" @default.
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