表皮生长因子受体 (EGFR) 外显子 20 插入占所有 EGFR 突变的比例高达 10%。接受批准的 EGFR 外显子 20 插入特异性抑制剂的患者的临床结果各不相同。尽管奥希替尼已在临床试验中证明了抗肿瘤活性，但其在插入 EGFR 外显子 20 的非小细胞肺癌 (NSCLC) 中的临床疗效和转化潜力仍有待确定。 在这项多中心 II 期研究中，针对携带 EGFR 外显子的晚期 NSCLC 患者标准化疗失败的 20 名插入者每天接受一次 80 毫克奥西替尼治疗。主要终点是研究者评估的客观缓解率 (ORR)，如实体瘤 1.1 版中的缓解评估标准所定义。次要终点是无进展生存期 (PFS)、总生存期 (OS) 和安全性。在 1 阶段入组的 15 名患者中，最佳反应最常见的是疾病稳定 (73.3%)，但不符合 1 阶段标准阈值（客观响应≥2/15）。截至数据截止，仍有两名患者仍在接受治疗。中位 PFS 和 OS 分别为 3.8（95% 置信区间 [CI]=1.7-5.5）个月和 6.5（95% CI=3.9-未达到）个月。不良事件（≥ 3 级）为贫血、高钙血症和肺炎（各 13.3%），以及乏力、股骨骨折、碱性磷酸盐增加、高钾血症、骨痛和氮质血症（各 6.7%）。在血浆中检测到的预先存在的 EGFR C797S 突变限制了奥希替尼的疗效。每天一次 80 毫克的奥希替尼疗效有限，并且在携带 EGFR 外显子 20 插入的晚期 NSCLC 中大多表现出疾病稳定和可接受的安全性。govIdentifier：NCT03414814。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Epidermal growth factor receptor (EGFR) exon 20 insertions account for up to 10% of all EGFR mutations. Clinical outcomes in patients receiving approved EGFR exon 20 insertion-specific inhibitors have been variable. Although osimertinib has demonstrated antitumor activity in clinical trials, its clinical efficacy and translational potential remain to be determined in non-small cell lung carcinoma (NSCLC) with EGFR exon 20 insertion.In this multicenter phase II study, patients with advanced NSCLC harboring EGFR exon 20 insertions for whom the standard chemotherapy failed received 80 mg osimertinib once daily. The primary endpoint was the investigator-assessed objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety profile.Among 15 patients enrolled at stage 1, the best response was most commonly disease stabilization (73.3 %), which did not meet the stage 1 threshold (objective response ≥ 2/15). As of data cutoff, two patients remained on the treatment. The median PFS and OS were 3.8 (95 % confidence interval [CI] = 1.7-5.5) months and 6.5 (95 % CI = 3.9-not reached) months, respectively. Adverse events (≥grade 3) were anemia, hypercalcemia, and pneumonia (13.3 % each), and asthenia, femur fracture, increased alkaline phosphate, hyperkalemia, bone pain, and azotemia (6.7 % each). Pre-existing EGFR C797S mutation detected in plasma limited the efficacy of osimertinib.Osimertinib at 80 mg once daily had limited efficacy and mostly showed disease stabilization with an acceptable safety profile in advanced NSCLC harboring EGFR exon 20 insertions.govIdentifier: NCT03414814.Copyright © 2024 Elsevier B.V. All rights reserved.