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=11

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=<sec><title>Background</title><p>Non-small cell lung cancer (NSCLC) patients with <italic>HER2</italic> 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 harboring <italic>HER2</italic> alterations are limited.</p></sec><sec><title>Patients and methods</title><p>We retrospectively included metastatic NSCLC patients harboring <italic>HER2</italic> 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.</p></sec><sec><title>Results</title><p>We included 54 patients harboring <italic>HER2</italic> mutations and 12 patients harboring <italic>HER2</italic> 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 <italic>HER2</italic> exon 20 mutations had numerically worse ORR (17% <italic>vs</italic> 42%), shorter PFS (2.6 <italic>vs</italic> 5.8 months, HR, 2.5; 95% CI, 1.2–5.5; <italic>P</italic> = 0.015) and OS (12.9 <italic>vs</italic> 33.3 months, HR, 4.4; 95% CI, 1.3–14.8; <italic>P</italic> = 0.009) than patients with other mutations. For HER2-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 13.4 months (95% CI, 0–27.6). The most frequently mutated genes in afatinib-resistant patients were <italic>TP53</italic> (44%) and <italic>EGFR</italic> (33%). Three afatinib-resistant patients harbored secondary <italic>HER2</italic> alterations.</p></sec><sec><title>Conclusions</title><p>Our results suggest that afatinib has a promising anti-tumor activity in patients with NSCLC harboring <italic>HER2</italic> alterations. To our knowledge, this is the largest retrospective study about the clinical activity of afatinib in NSCLC patients with <italic>HER2</italic> alterations.</p></sec>