Li Y, Chen L A
Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing 100853, China (Currently address: Department of Respiratory Diseases, 309 Hospital of PLA, Beijing 100091, China).
Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing 100853, China.
Zhonghua Zhong Liu Za Zhi. 2017 Dec 23;39(12):881-884. doi: 10.3760/cma.j.issn.0253-3766.2017.12.001.
Precise medicine is an emerging clinical therapeutic concept based on genomic and genetic information of patients. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is an important component of precise therapy for lung cancer patients. EGFR mutations occur mainly in exon 18 to 21, in which exon 19 deletion and exon 21 L858R point mutation that are known as sensitive mutations account for nearly 45% and 40%, respectively. Except for the above two mutations and T790M point mutation, the rest are rare mutations, including Ins19, Ins20, E709, G719, S768, L861 and some compound mutations. Some previous retrospective studies of small sample size and case reports showed that most of EGFR exon19 (Ins), exon 21 (L861), exon 18 (G719X) and exon20 (S768I) mutations were sensitive to TKIs. And although the exon 20 insertion mutation is usually predicted to the first and second generations of EGFR-TKIs resistance, some specific types are sensitive to the third generation of EGFR-TKIs. Currently, targeted drugs for Ins20 -Ap32788 mutation has entered into clinical trials. Patients with complex mutations have similar efficacy on EGFR-TKIs in comparison with those with single sensitivity mutations. In conclusion, when patients with rare sensitive mutations received EGFR-TKIs therapy, the efficacy and progression-free survival time is similar to or slightly lower than those with classical sensitive mutations, whereas it is higher than those with wild-type EGFR. Compared with the first generation of EGFR-TKIs, second generation EGFR-TKIs may be more suitable for the treatment of lung cancer patients harboring rare sensitive EGFR mutations.
精准医学是一种基于患者基因组和遗传信息的新兴临床治疗理念。表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)是肺癌患者精准治疗的重要组成部分。EGFR突变主要发生在18至21外显子,其中被称为敏感突变的19外显子缺失和21外显子L858R点突变分别占近45%和40%。除上述两种突变和T790M点突变外,其余均为罕见突变,包括Ins19、Ins20、E709、G719、S768、L861以及一些复合突变。以往一些小样本回顾性研究和病例报告显示,大多数EGFR 19外显子(Ins)、21外显子(L861)、18外显子(G719X)和20外显子(S768I)突变对TKIs敏感。虽然20外显子插入突变通常被预测对第一代和第二代EGFR-TKIs耐药,但一些特定类型对第三代EGFR-TKIs敏感。目前,针对Ins20 -Ap32788突变的靶向药物已进入临床试验。与单敏感突变患者相比,复杂突变患者接受EGFR-TKIs治疗的疗效相似。总之,罕见敏感突变患者接受EGFR-TKIs治疗时,疗效和无进展生存时间与经典敏感突变患者相似或略低,但高于野生型EGFR患者。与第一代EGFR-TKIs相比,第二代EGFR-TKIs可能更适合治疗携带罕见敏感EGFR突变的肺癌患者。