罕见的 EGFR E709-T710delinsX：非小细胞肺癌患者的分子特征和对阿法替尼治疗的优越反应。

Rare EGFR E709-T710delinsX: Molecular characteristics and superior response to afatinib treatment in NSCLC patients.

机构信息

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, People's Republic of China.

Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 Zhongshan Road, Nanjing 210002, People's Republic of China.

出版信息

Lung Cancer. 2022 Oct;172:117-123. doi: 10.1016/j.lungcan.2022.08.012. Epub 2022 Aug 22.

DOI:10.1016/j.lungcan.2022.08.012

PMID:36063602

Abstract

OBJECTIVES

Currently, whether patients with rare epidermal growth factor receptor (EGFR) mutations could benefit from EGFR tyrosine kinase inhibitors (TKIs) demands further studies. Limited clinical data are available regarding the molecular characteristics and clinical response in non-small-cell lung cancer (NSCLC) patients harboring EGFR E709-T710delinsX mutations, a rare mutation type in exon 18 of EGFR. In this study, we aimed to explore the molecular distribution and clinical outcome of EGFR E709-T710delinsX mutated Chinese patients.

METHODS

Next-generation sequencing (NGS) tests were performed in 15,078 NSCLC patients. A multicenter retrospective cohort involving 17 advanced lung cancer patients with EGFR E709-T710delinsX was collected to evaluate clinical responses to diverse therapies. In silico protein structure modeling was conducted to predict drug response.

RESULTS

5905 EGFR mutant patients (39.2%, 5905/15078) were identified, with 26 cases (0.44%, 26/5905) harbored EGFR E709-T710delinsD. Afatinib showed a better overall objective response rate (ORR) compared with the first-generation (1G) EGFR TKIs and chemotherapy with significant difference. Superior progression free survival (PFS) was also observed in patients treated with afatinib (afatinib 10.85 m vs 1G EGFR TKIs 4.0 m vs chemotherapy 2.8 m, p = 0.0007). In silico protein structure modeling predicts better binding of afatinib with EGFR E709-T710delinsD compared with other EGFR TKIs.

CONCLUSIONS

This is the largest studies for EGFR E709-T710delinsX, with 26 cases with EGFR E709-T710delinsX being identified (0.44% in EGFR mutant NSCLC, 0.17% in NSCLC patients). This study also firstly revealed that afatinib might exert superior antitumor activity to the 1G EGFR TKIs and chemotherapy in EGFR E709-T710delinsX mutant patients.

摘要

目的

目前，携带罕见表皮生长因子受体（EGFR）突变的患者是否能从 EGFR 酪氨酸激酶抑制剂（TKI）中获益，仍需要进一步研究。关于 EGFR 外显子 18 中 EGFR E709-T710delinsX 突变的非小细胞肺癌（NSCLC）患者的分子特征和临床反应，仅有有限的临床数据。本研究旨在探讨中国 EGFR E709-T710delinsX 突变患者的分子分布和临床结局。

方法

对 15078 例 NSCLC 患者进行下一代测序（NGS）检测。收集了 17 例晚期肺癌患者的多中心回顾性队列，这些患者携带 EGFR E709-T710delinsX，以评估不同治疗方法的临床反应。进行了计算机蛋白质结构建模，以预测药物反应。

结果

共鉴定出 5905 例 EGFR 突变患者（39.2%，5905/15078），其中 26 例（0.44%，26/5905）存在 EGFR E709-T710delinsD。与第一代（1G）EGFR TKI 和化疗相比，阿法替尼的总客观缓解率（ORR）更好，差异具有统计学意义。接受阿法替尼治疗的患者的无进展生存期（PFS）也更长（阿法替尼 10.85m 比 1G EGFR TKI 4.0m 比化疗 2.8m，p=0.0007）。计算机蛋白质结构建模预测阿法替尼与 EGFR E709-T710delinsD 的结合优于其他 EGFR TKI。

结论

这是 EGFR E709-T710delinsX 最大的研究，共鉴定出 26 例 EGFR E709-T710delinsX（0.44%在 EGFR 突变 NSCLC 中，0.17%在 NSCLC 患者中）。本研究还首次表明，在 EGFR E709-T710delinsX 突变患者中，阿法替尼可能比 1G EGFR TKI 和化疗具有更好的抗肿瘤活性。