背景:对于表皮生长因子受体(EGFR)外显子19缺失和外显子21L858R突变的IV期非小细胞肺癌患者,奥希替尼是标准的治疗方法.研究奥希替尼在EGFR外显子18G719X患者中的活性和安全性,外显子20S768I,或外显子21L861Q突变具有临床意义。
方法:确认EGFR外显子18G719X的IV期非小细胞肺癌患者,外显子20S768I,或外显子21L861Q突变合格。患者需要有可测量的疾病,东部肿瘤协作组的表现状态为0或1,器官功能充足。患者需要初治EGFR酪氨酸激酶抑制剂。主要目标是客观反应率,次要目标是无进展生存期,安全,和总体生存率。该研究采用两阶段设计,计划在第一阶段招募17名患者,由于累积缓慢,研究在第一阶段后终止。
结果:在2018年5月至2020年3月之间,有17名患者入选并接受研究治疗。患者的中位年龄为70岁(四分位距62-76),大多数是女性(n=11),性能状态为1(n=10),5例患者在基线时出现脑转移。客观反应率为47%[95%置信区间(CI)23%至72%],并且观察到的射线照相响应是部分响应(n=8),疾病稳定(n=8),和进行性疾病(n=1)。中位无进展生存期为10.5个月(95%CI5.0-15.2个月),中位OS为13.8个月(95%CI7.3-29.2个月)。中位治疗时间为6.1个月(范围3.6-11.9个月),最常见的不良事件(不考虑归因)是腹泻,疲劳,厌食症,减肥,和呼吸困难。
结论:本试验提示奥希替尼在这些不常见EGFR突变患者中具有活性。
For patients with stage IV non-small-cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions and exon 21 L858R mutations, osimertinib is the standard of care. Investigating the activity and safety of osimertinib in patients with EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations is of clinical interest.
Patients with stage IV non-small-cell lung cancer with confirmed EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations were eligible. Patients were required to have measurable disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients were required to be EGFR tyrosine kinase inhibitor-naive. The primary objective was objective response rate, and secondary objectives were progression-free survival, safety, and overall survival. The study used a two-stage design with a plan to enroll 17 patients in the first stage, and the study was terminated after the first stage due to slow accrual.
Between May 2018 and March 2020, 17 patients were enrolled and received study therapy. The median age of patients was 70 years (interquartile range 62-76), the majority were female (n = 11), had a performance status of 1 (n = 10), and five patients had brain metastases at baseline. The objective response rate was 47% [95% confidence interval (CI) 23% to 72%], and the radiographic responses observed were partial response (n = 8), stable disease (n = 8), and progressive disease (n = 1). The median progression-free survival was 10.5 months (95% CI 5.0-15.2 months), and the median OS was 13.8 months (95% CI 7.3-29.2 months). The median duration on treatment was 6.1 months (range 3.6-11.9 months), and the most common adverse events (regardless of attribution) were diarrhea, fatigue, anorexia, weight loss, and dyspnea.
This trial suggests osimertinib has activity in patients with these uncommon EGFR mutations.