AUTHOR=Song Zhengbo , Lv Dongqing , Chen Shiqing , Huang Jianhui , Wang Liping , Xu Shuguang , Chen Huafei , Wang Guoqiang , Lin Quan 

TITLE=Efficacy and Resistance of Afatinib in Chinese Non-Small Cell Lung Cancer Patients With HER2 Alterations: A Multicenter Retrospective Study

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.657283

DOI=10.3389/fonc.2021.657283

ISSN=2234-943X

ABSTRACT=Background: Non-small cell lung cancer patients (NSCLC) with HER2 mutations and amplification may benefit from HER2-targeted therapy, including afatinib. However, the data regarding the clinical activity of afatinib in Chinese patients with NSCLC harboringHER2 alterations are limited.
Patients and methods: We retrospectively included metastatic NSCLC patients harboringHER2 alterations who treated with afatinib. The clinical outcomes included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The genomic profiling data after progression on afatinib were analyzed. 
Results: We included 54 patients harboring HER2 mutations and 12 patients harboring HER2 amplification. The ORR was 24% (95% CI, 16-36%), the median PFS was 3.3 months (95% CI, 2.2-4.4), and the median OS was 13.9 months (95% CI, 11.4-16.5). Patients with HER2 exon 20 mutations had numerically worse ORR (17% vs 42%), shorter PFS (2.6 vs 5.8 months, HR, 2.5; 95% CI, 1.2-5.5; P = 0.015) and OS (12.9 vs 33.3 months, HR, 4.4; 95% CI, 1.3-14.8; P = 0.009) than patients with other mutations.ForHER2-amplified patients, the ORR was 33% (95% CI, 14-61%), the median PFS was 3.3 months (95% CI, 2.6-4.0), and the median OS was 13.4months (95% CI, 0-27.6). The most frequently mutated genes in afatinib-resistant patients were TP53 (44%), and EGFR (33%). Three afatinib-resistant patients harbored secondary HER2 alterations.
Conclusions: Our results suggest that afatinib has a promising anti-tumor activity in patients with NSCLC harboring HER2alterations. To our knowledge, this is the largest retrospective study about the clinical activity of afatinib in NSCLC patients with HER2 alterations.