Department of Respiratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Medical Oncology, Shanghai Pulmonary Hospital,Tongji University, Tongji University Medical School Cancer Institute, Shanghai, China.
BMC Cancer. 2018 Feb 6;18(1):148. doi: 10.1186/s12885-018-4075-5.
Although EGFR-TKI is the preferred treatment for NSCLC patients with sensitive mutations, subsequent drug resistance is almost inevitable. The specific mechanisms of EGFR-TKI drug resistance can be identified through repeat biopsy.
To better understand the clinical characteristics of TKI resistance in NSCLC patients, we retrospectively reviewed studies of acquired TKI drug resistance using repeat biopsy from the last decade. The relevant literature was retrieved from January 2005 to August 2015 in the databases Medline and Embase. The search terms were NSCLC or non-small cell lung cancer and T790 M.
A total of 478 patients with NSCLC tested by repeated biopsy were confirmed to have acquired TKI resistance. Analysis indicated that 240 patients (50.21%) of the 478 patients with acquired TKI drug resistance had the T790 M mutation. The detection rate of T790 M in different repeat biopsy sites was also different, with the highest positive rate in the lymph nodes (60%) and the lowest detection rate in cerebrospinal fluid (less than 5%). In addition, patients with T790 M had longer overall survival compared to those without the mutation (P < 0.05). Of the 240 patients with T790 M mutations, 213 patients showed results consistent with the mutation analysis before TKI treatment, and the rate of patients with the L858R point mutation along with the T790 M mutation was lower than that of patients with the exon 19 deletion (36.42% to 58.30%).
T790 M occurred more frequently in patients with the exon 19 deletion than in those with exon 21 L858R, which gave the survival benefit of the T790 M mutation and may explain why patients with the exon 19 deletion had an improved overall survival.
虽然表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）是治疗具有敏感突变的非小细胞肺癌（NSCLC）患者的首选药物，但几乎不可避免会发生后续的药物耐药。通过重复活检可以确定 EGFR-TKI 耐药的具体机制。
为了更好地了解 NSCLC 患者 TKI 耐药的临床特征，我们回顾性分析了过去十年中使用重复活检获得的 TKI 耐药相关研究。检索了 Medline 和 Embase 数据库中 2005 年 1 月至 2015 年 8 月的相关文献，检索词为 NSCLC 或非小细胞肺癌和 T790M。
共有 478 例经重复活检证实获得 EGFR-TKI 耐药的 NSCLC 患者，其中 240 例（50.21%）患者存在 T790M 突变。不同重复活检部位 T790M 的检出率也不同，其中淋巴结的阳性率最高（60%），脑脊液的检出率最低（<5%）。此外，与无 T790M 突变的患者相比，携带 T790M 突变的患者总生存期更长（P<0.05）。在 240 例 T790M 突变患者中，213 例患者与 TKI 治疗前的突变分析结果一致，L858R 点突变伴 T790M 突变的患者比例低于外显子 19 缺失（36.42%至 58.30%）。
外显子 19 缺失患者中 T790M 突变的发生率高于外显子 21 L858R 突变，这为 T790M 突变带来了生存获益，可能解释了外显子 19 缺失患者总生存期改善的原因。
