Toward the next generation EGFR inhibitors: an overview of osimertinib resistance mediated by EGFR mutations in non-small cell lung cancer

Table 1 The next generation TKIs/TKIs combination currently undergoing development and clinical trials

The fourth – generation TKI	Suppression	Study	Outcome	References
Brigatinib	EGFR ex19del/T790M/C797S Mutation	In vitro and in vivo research	Effective	Uchibori K et al. 2017 [48]
Brigatinib + Cetuximab	EGFR ex19del/T790M/cis-C797S Mutation	A retrospective analysis of 15 patients	ORR 60%; DCR 100%	Wang Y et al., 2020 [89]
Brigatinib + Cetuximab + Osimertinib	EGFR L858R/T790M/cis-C797S Mutation	A case report	Partial remission was observed after one month of the treatment	Zhao J et al., 2018 [90]
EAI045 + Cetuxi mab	EGFR ex19del/T790M/C797S Mutation	In vitro and in vivo research	Effective	Jia Y et al., 2016 [91]
CH7233163	EGFR ex19del/T790M/C797S Mutation	In vivo resarch	Effective	Kashima K et al., 2020 [92]
BLU-945	EGFR + /T790M;EGFR + /T790M/C797S Mutation	In a phase ½ clinical trial (NCT 04862780)	In progress	Eno MS et al., 2022 [93]

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