This study investigated the effect of afatinib, a dual inhibitor of HER2 and EGFR, on patient-derived cancer models with the HER2 extracellular domain mutation E401G. A xenograft (PDX) and a cancer tissue-originated spheroid (CTOS) were generated from a patient's cancer with amplified HER2 E401G. Afatinib demonstrated superior efficacy in reducing tumor size compared to lapatinib or trastuzumab plus pertuzumab in both PDX and CTOS models. Afatinib also significantly reduced HER2 copy number. In contrast, trastuzumab plus pertuzumab was most effective in H2170 xenografts with wild-type HER2 amplification. The findings suggest that afatinib is a promising therapeutic option for cancers with amplified HER2 E401G due to its dual inhibition of HER2 and EGFR.
