Introduction

Epidermal growth factor receptor (EGFR) exon 20 insertions comprise 4-9% of EGFR mutated non-small-cell lung cancer (NSCLC). Despite being an oncogenic driver, they are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). We hypothesized that dual EGFR blockade with afatinib, an irreversible EGFR TKI, and cetuximab, a monoclonal antibody against EGFR, could induce tumor responses.

Methods

Four patients with EGFR exon 20 insertion positive NSCLC were treated with afatinib 40 mg once daily and cetuximab 250-500 mg/m² every two weeks.

Results

All patients had stage IV adenocarcinoma of the lung harboring an EGFR exon 20 insertion mutation. Previous lines of treatment consisted of platinum doublet chemotherapy (n=4) and EGFR TKI (n=2). Three out of four patients showed a partial response according to RECIST 1.1. Median progression-free survival was 5.4 months (95% confidence interval 0.0 – 14.2 months; range 2.7 – 17.6 months). Toxicity was manageable with appropriate skin management and dose reduction being required in two patients.

Conclusions

Dual EGFR blockade with afatinib and cetuximab may induce tumor responses in patients with EGFR exon 20 insertion positive NSCLC.

中文翻译：

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简要报告：阿法替尼和西妥昔单抗治疗EGFR外显子20插入阳性的4例晚期非小细胞肺癌患者

介绍

表皮生长因子受体（EGFR）外显子20插入占EGFR突变的非小细胞肺癌（NSCLC）的4-9％。尽管是致癌的驱动因素，但它们与对EGFR酪氨酸激酶抑制剂（TKI）的主要耐药性相关。我们假设用不可逆的EGFR TKI阿法替尼和抗EGFR的单克隆抗体西妥昔单抗双重EGFR阻断可诱导肿瘤反应。

方法

EGFR外显子20插入阳性NSCLC的四名患者每天接受afatinib 40 mg治疗，每两周接受250-500 mg / m ²西妥昔单抗治疗。

结果

所有患者均患有EGFR外显子20插入突变的肺IV期腺癌。先前的治疗方法包括铂类双重化疗（n = 4）和EGFR TKI（n = 2）。根据RECIST 1.1，四分之三的患者表现出部分反应。中位无进展生存期为5.4个月（95％置信区间为0.0 – 14.2个月；范围为2.7 – 17.6个月）。通过适当的皮肤管理和两名患者的剂量减少，可以控制毒性。

结论

阿法替尼和西妥昔单抗双重EGFR阻断剂可能在EGFR外显子20插入阳性NSCLC患者中引起肿瘤反应。