表皮生长因子受体外显子 20 插入突变：晚期非小细胞肺癌的临床病理特征和治疗结局。
EGFR Exon 20 Insertion Mutations: Clinicopathological Characteristics and Treatment Outcomes in Advanced Non-Small Cell Lung Cancer.
机构信息
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
出版信息
Clin Lung Cancer. 2021 Nov;22(6):e859-e869. doi: 10.1016/j.cllc.2021.04.009. Epub 2021 May 16.
BACKGROUND
Epidermal growth factor receptor gene (EGFR) exon 20 insertion (ex20-ins) mutations are an uncommon and heterogeneous group of non-small cell lung cancers (NSCLCs), resistant to conventional EGFR tyrosine kinase inhibitors (TKIs). Characteristics and outcomes of patients with EGFR ex20-ins have not been fully established; we sought to clarify them using a multinational patient database.
PATIENTS AND METHODS
Patients with NSCLC from six Australian institutions with EGFR exon 20 mutations (ex20-mut), excluding T790M, were retrospectively reviewed. Clinical characteristics and outcomes with systemic treatments were collected and analyzed using comparative statistics.
RESULTS
Among 109 patients with ex20-mut, 61% were females and 75% were Caucasians. More males presented with de novo metastatic disease (84% vs. 51%; P = .002). Central nervous system (48%) and liver (24%) metastases were common within metastatic patients (n = 86). Thirty-nine patients received platinum-based chemotherapy (PBC) and achieved a 43% objective response rate (ORR), median progression-free survival (mPFS) of 6.9 months, and median overall survival (mOS) of 31.0 months. Twenty-three of the patients with ex20-ins received conventional TKIs, resulting in an ORR of 13%, mPFS of 3.4 months (95% confidence interval [CI], 1.91-6.25), and mOS of 31.0 months (95% CI, 15.09-not reached). Nine patients with S786I mutations received TKIs, resulting in an ORR of 50%, mPFS of 18.2 months (2.79-not reached), and mOS of 33.4 months (95% CI, 16.14-not reached). Twenty-three patients received immune checkpoint inhibitor monotherapy (ICIm), resulting in an ORR of 4%, mPFS of 2.6 months (95% CI, 1.91-4.83), and mOS of 30.8 months (95% CI, 17.62-41.62).
CONCLUSION
Although phenotypically similar to patients with common EGFR mutations, patients with EGFR ex20-mut had worse survival, perhaps due to the lack of targeted therapies. Chemotherapy was superior to conventional EGFR TKIs in patients with EGFR ex20-ins, although there was moderate activity of TKIs in S768I mutations. ICIm was ineffective.
背景
表皮生长因子受体基因（EGFR）外显子 20 插入（ex20-ins）突变是非小细胞肺癌（NSCLC）中一种不常见且异质性的群体，对传统的 EGFR 酪氨酸激酶抑制剂（TKI）耐药。EGFR ex20-ins 患者的特征和结局尚未完全确定；我们试图使用一个多国家的患者数据库来阐明这些问题。
方法
回顾性分析了来自澳大利亚 6 家机构的 NSCLC 患者的临床资料，这些患者 EGFR 外显子 20 突变（ex20-mut），不包括 T790M。收集并分析了系统治疗的临床特征和结局，并采用比较统计学方法进行分析。
结果
在 109 例 ex20-mut 患者中，61%为女性，75%为白种人。更多男性表现为初诊转移性疾病（84%比 51%；P =.002）。在转移性患者（n=86）中，中枢神经系统（48%）和肝脏（24%）转移很常见。39 例患者接受铂类化疗（PBC），客观缓解率（ORR）为 43%，无进展生存期（mPFS）为 6.9 个月，总生存期（mOS）为 31.0 个月。23 例 ex20-ins 患者接受常规 TKI 治疗，ORR 为 13%，mPFS 为 3.4 个月（95%CI，1.91-6.25），mOS 为 31.0 个月（95%CI，15.09-未达到）。9 例 S786I 突变患者接受 TKI 治疗，ORR 为 50%，mPFS 为 18.2 个月（2.79-未达到），mOS 为 33.4 个月（95%CI，16.14-未达到）。23 例患者接受免疫检查点抑制剂单药治疗（ICIm），ORR 为 4%，mPFS 为 2.6 个月（95%CI，1.91-4.83），mOS 为 30.8 个月（95%CI，17.62-41.62）。
结论
尽管表型上与常见的 EGFR 突变患者相似，但 EGFR ex20-mut 患者的生存情况较差，这可能是由于缺乏靶向治疗。在 EGFR ex20-ins 患者中，化疗优于常规 EGFR TKI，尽管 S768I 突变的 TKI 有一定的活性。ICIm 无效。
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