Zhao Lingling, Wang Zhen, Du Haiwei, Chen Songan, Wang Pingli
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Burning Rock Biotech, Guangzhou, China.
Front Oncol. 2021 Apr 7;11:605853. doi: 10.3389/fonc.2021.605853. eCollection 2021.
The rapid development of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring mutations including but not limited to exon 19 deletions (19 del) and point mutation L858R in exon 21. However, the efficacy of EGFR-TKIs in patients with rare mutations, such as kinase domain duplication (KDD), remains elusive. -KDD often results from in-frame tandem duplication of exons 18-25, causing subsequent constitutive activation of EGFR signaling. Several case reports have revealed the efficacies of EGFR-TKIs in advanced lung adenocarcinoma (LUAD) with -KDD but yielded variable antitumor responses. In the present study, we report a 61-year-old male patient diagnosed with T1N3M0 (stage IIIB) LUAD harboring -KDD involving exons 18-25. He was treated with afatinib and achieved partial response (PR) with progression-free survival (PFS) of 12 months and counting. Our work, confirming -KDD as an oncogenic driver and therapeutic target, provides clinical evidence to administer EGFR-TKIs in patients with advanced LUAD harboring -KDD.
表皮生长因子受体(EGFR)-酪氨酸激酶抑制剂(TKIs)的迅速发展彻底改变了对携带包括但不限于第19外显子缺失(19 del)和第21外显子点突变L858R等突变的晚期或转移性非小细胞肺癌(NSCLC)患者的治疗。然而,EGFR-TKIs在具有罕见突变(如激酶结构域重复(KDD))的患者中的疗效仍不明确。-KDD通常由第18-25外显子的框内串联重复导致,进而引起EGFR信号的持续激活。几例病例报告显示了EGFR-TKIs在伴有-KDD的晚期肺腺癌(LUAD)中的疗效,但产生了不同的抗肿瘤反应。在本研究中,我们报告了一名61岁男性患者,诊断为T1N3M0(IIIB期)LUAD,伴有涉及第18-25外显子的-KDD。他接受了阿法替尼治疗,获得了部分缓解(PR),无进展生存期(PFS)为12个月且仍在持续。我们的工作证实了-KDD是一种致癌驱动因素和治疗靶点,为对伴有-KDD的晚期LUAD患者使用EGFR-TKIs提供了临床证据。