Department of Thoracic Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
J Thorac Oncol. 2018 Aug;13(8):1222-1226. doi: 10.1016/j.jtho.2018.04.012. Epub 2018 Apr 24.
EGFR exon 20 insertions comprise 4% to 9% of EGFR mutated 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.
Four patients with EGFR exon 20 insertion-positive NSCLC were treated with afatinib 40 mg once daily and cetuximab 250 mg/m to 500 mg/m every 2 weeks.
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 of four patients showed a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Median progression-free survival was 5.4 months (95% confidence interval: 0.0 - 14.2 months; range 2.7 months - 17.6 months). Toxicity was manageable with appropriate skin management and dose reduction being required in two patients.
Dual EGFR blockade with afatinib and cetuximab may induce tumor responses in patients with EGFR exon 20 insertion-positive NSCLC.
EGFR 外显子 20 插入占 EGFR 突变 NSCLC 的 4%至 9%。尽管是致癌驱动因素，但它们与 EGFR 酪氨酸激酶抑制剂 (TKI) 的原发性耐药有关。我们假设使用不可逆的 EGFR TKI 阿法替尼和针对 EGFR 的单克隆抗体西妥昔单抗进行双重 EGFR 阻断可能会诱导肿瘤反应。
4 名 EGFR 外显子 20 插入阳性 NSCLC 患者接受阿法替尼 40 mg 每日一次和西妥昔单抗 250 mg/m 至 500 mg/m 每 2 周一次治疗。
所有患者均患有 IV 期肺腺癌，携带 EGFR 外显子 20 插入突变。先前的治疗方案包括铂类双联化疗 (n=4) 和 EGFR TKI (n=2)。根据实体瘤反应评估标准 (RECIST 1.1)，4 名患者中有 3 名显示部分缓解。中位无进展生存期为 5.4 个月（95%置信区间：0.0-14.2 个月；范围 2.7 个月-17.6 个月）。通过适当的皮肤管理可控制毒性，两名患者需要减少剂量。
阿法替尼和西妥昔单抗的双重 EGFR 阻断可能会诱导 EGFR 外显子 20 插入阳性 NSCLC 患者的肿瘤反应。
