EGFR exon 19 insertion EGFR-K745_E746insIPVAIK and others with rare XPVAIK amino-acid insertions: Preclinical and clinical characterization of the favorable therapeutic window to all classes of approved EGFR kinase inhibitors

•EGFR-K745_E746insIPVAIK and other exon 19 insertion mutations (<0.8% of mutations) at the structural modeling level resemble EGFR inhibitor-sensitizing mutants.•An important unmet need is the characterization of therapeutic windows plus clinical outcomes of exon 19 XPVAIX amino-acid insertion mutations to available EGFR TKIs.•Preclinical models of EGFR-K745_E746insIPVAIK had sensitivity to approved EGFR TKIs but therapeutic windows most akin to EGFR-L861Q and -A763_Y764insFQEA than classical mutants.•This is the largest preclinical/clinical report to highlight that exon 19 XPVAIX amino-acid insertions are rare but sensitive to clinically available inhibitors.