Abstract
BackgroundNon-small cell lung cancer (NSCLC) patients 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 harboring HER2 alterations are limited.Patients and methodsWe retrospectively included metastatic NSCLC patients harboring HER2 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.ResultsWe 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. 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 TP53 (44%) and EGFR (33%). Three afatinib-resistant patients harbored secondary HER2 alterations.ConclusionsOur results suggest that afatinib has a promising anti-tumor activity in patients with NSCLC harboring HER2 alterations. To our knowledge, this is the largest retrospective study about the clinical activity of afatinib in NSCLC patients with HER2 alterations.
Highlights
Lung cancer is one of the most common malignant tumors, causing approximate 25% of the total cancer-related deaths [1]
Recent studies reported that non-small cell lung cancer (NSCLC) patients with HER2 exon 20 insertions had an overall response rate (ORR) of 13–19% from afatinib treatment [14, 15, 18]
The other two patients respectively harbored H878Y and L1173V, and the PFS were 22.7 and 25.0 months, respectively. These results suggest that the patients with HER2 other mutations except exon 20 mutations could benefit from HER2-targeted inhibitors
Summary
Lung cancer is one of the most common malignant tumors, causing approximate 25% of the total cancer-related deaths [1]. About 85% of patients with lung cancer are histologically diagnosed as non-small cell lung cancer (NSCLC) [2]. Human epidermal growth factor receptor 2 (HER2, known as ERBB2) is a cancer driver gene, and 1.7–3% of NSCLC patients harbor HER2 mutations [5,6,7]. T-DM1 is the only recommended HER2-targeted inhibitor for HER2-mutated NSCLC patients by National Comprehensive Cancer Network (NCCN) Guidelines, with an overall response rate (ORR) of 44% [10]. No HER2-targeted therapy has been approved for patients with NSCLC harboring HER2 mutations or amplification. Non-small cell lung cancer (NSCLC) patients with HER2 mutations and amplification may benefit from HER2-targeted therapy, including afatinib. The data regarding the clinical activity of afatinib in Chinese patients with NSCLC harboring HER2 alterations are limited
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