OBJECTIVES Epidermal growth factor receptor (EGFR) exon 20 insertions comprise 4-10 % of EGFR mutations in non-small cell lung cancer (NSCLC) and are associated with primary resistance to first and second generation EGFR tyrosine kinase inhibitors (TKIs). In vitro and preclinical animal studies have shown that osimertinib exerts antitumor activity against EGFR exon 20 mutation positive NSCLC. We report on a cohort of advanced stage NSCLC patients who harbor an EGFR exon 20 mutation and received osimertinib treatment. MATERIAL AND METHODS Twenty-one patients were treated with osimertinib 80 or 160 mg once daily from April 2016 to June 2018, in four institutions in the Netherlands. Data were obtained retrospectively. Progression free survival (PFS), disease control rate (DCR), overall survival (OS) and objective response rate (ORR) were assessed using RECIST v1.1. RESULTS Thirteen patients received prior platinum-based chemotherapy, and three patients a first - or second generation EGFR TKI. We observed 1 partial response, 17 patients with stable disease and 3 with progressive disease as best response to osimertinib (ORR 5 %). Median PFS was 3.6 (95 % CI, 2.6-4.5) months. PFS did not differ for patients with co-occurring TP53 mutations (p = 0.937). The DCR at three months was 71 %. Median OS was 8.7 (95 % CI, 1.1-16.4) months. CONCLUSION Osimertinib has limited antitumor activity in patients with EGFR exon 20 mutated NSCLC, with an ORR of 5 %.

中文翻译：

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奥西替尼治疗EGFR外显子20突变阳性的非小细胞肺癌患者。

目的非小细胞肺癌（NSCLC）中表皮生长因子受体（EGFR）外显子20的插入包含4-10％的EGFR突变，并与对第一代和第二代EGFR酪氨酸激酶抑制剂（TKIs）的原发耐药有关。体外和临床前动物研究表明，奥西替尼对EGFR外显子20突变阳性NSCLC具有抗肿瘤活性。我们报告了一个晚期NSCLC患者队列，这些患者具有EGFR外显子20突变并接受了osimertinib治疗。材料与方法自2016年4月至2018年6月，每天在荷兰的四个机构中对21例患者进行一次奥西替尼80或160 mg每日一次的治疗。回顾性获得数据。无进展生存期（PFS），疾病控制率（DCR），使用RECIST v1.1评估了总生存期（OS）和客观反应率（ORR）。结果13例患者先前接受了铂类化学疗法，而3例患者是第一代或第二代EGFR TKI。我们观察到1个部分缓解，17例疾病稳定的患者和3例进行性疾病的患者对osimertinib的最佳反应（ORR 5％）。PFS中位数为3.6（95％CI，2.6-4.5）个月。TP53突变患者的PFS没有差异（p = 0.937）。三个月时的DCR为71％。OS中位数为8.7（95％CI，1.1-16.4）个月。结论Osimertinib对EGFR外显子20突变的NSCLC患者的抗肿瘤活性有限，ORR为5％。17例稳定疾病患者和3例进行性疾病患者对奥西替尼的最佳反应（ORR 5％）。PFS中位数为3.6（95％CI，2.6-4.5）个月。TP53突变患者的PFS没有差异（p = 0.937）。三个月时的DCR为71％。OS中位数为8.7（95％CI，1.1-16.4）个月。结论Osimertinib对EGFR外显子20突变的NSCLC患者的抗肿瘤活性有限，ORR为5％。17例稳定疾病患者和3例进行性疾病患者对奥西替尼的最佳反应（ORR 5％）。PFS中位数为3.6（95％CI，2.6-4.5）个月。TP53突变患者的PFS没有差异（p = 0.937）。三个月时的DCR为71％。OS中位数为8.7（95％CI，1.1-16.4）个月。结论Osimertinib对EGFR外显子20突变的NSCLC患者的抗肿瘤活性有限，ORR为5％。