ERBB3 V659E

Fam-trastuzumab-deruxtecan-nxki (T-DXd) is approved for NSCLC with activating ERBB2 mutations...One patient with an ERBB2 transmembrane domain mutation (V659E) achieved a partial response with trastuzumab-emtansine (T-DM1)... Activating ERBB2/ERBB3 alterations can be identified by tissue or plasma next-generation sequencing. Alterations in both genes are more frequently observed in non-squamous NSCLC. Most ERBB2 activating mutations are in the kinase domain and most ERBB3 activating mutations are found in the extracellular domain.

P2, N=25, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Sep 2022

P2, N=25, Active, not recruiting, City of Hope Medical Center | N=40 --> 25 | Trial completion date: Oct 2021 --> Dec 2022

P2, N=40, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2020 --> Oct 2021 | Trial primary completion date: Oct 2020 --> Oct 2021

One patient with V659E responded well to ERBB2 inhibitor lapatinib plus capecitabine as well as subsequent afatinib treatment upon progression. Our study provides valuable insights into the distribution of ERBB2 TMD mutations by employing the largest Asian lung cancer cohort thus far. Patients with ERBB2 TMD mutations who received afatinib, a pan-ERBB inhibitor, demonstrated mixed responses, posing the urgent need to develop more effective therapeutic strategy for patients who carry ERBB2 TMD mutations.