免疫联合化疗逆转MET D1228E合并EGFR L858R介导的MET 14外显子跳跃突变肺腺癌耐药

Immunotherapy combined with chemotherapy reversed MET D1228E and EGFR L858R-mediated drug resistance of lung adenocarcinoma with MET 14 exon skipping mutation

摘要:

1例间质-上皮细胞转化因子（MET）14外显子跳跃突变的Ⅳ期肺腺癌患者服用MET酪氨酸激酶抑制剂（TKI）赛沃替尼8.5个月后疾病进展（PD），耐药基因检测提示出现新的MET 19外显子D1228E及表皮生长因子受体（EGFR）21外显子L858R错义突变。遂将治疗方案改为EGFR-TKI奥希替尼联合克唑替尼治疗，23天后临床症状加重，复查CT提示PD。经多学科诊疗（MDT）讨论，将三线治疗方案改为以铂类为基础的化疗联合免疫治疗，期间最佳疗效评价为部分缓解（PR），无进展生存期为6.4个月。目前，对于MET-TKIs耐药后新发二次突变合并EGFR突变的患者尚无标准治疗方案，本案例为此类患者提供了一种可供参考的后续治疗方案。

Abstract:

A patient with stage Ⅳ lung adenocarcinoma and harboring mesenchymal-epithelial transition factor (MET) exon 14 skipping mutation, had disease progression (PD) after treatment for 8.5 months with savolitinib, a tyrosine kinase inhibitor (TKI). Then the results of next generation sequencing showed that MET exon 14 skipping mutation was accompanied with the newly occurred missense mutation of MET exon 19 D1228E and epidermal growth factor receptor (EGFR) exon 21 L858R. Subsequently, the treatment regimen was changed to EGFR-TKI osimertinib combined with crizotinib as the second-line treatment. The clinical symptoms worsened 23 days later, and the reexamination of CT showed PD. After the discussion of multidisciplinary treatment (MDT), the third-line treatment was changed to immunotherapy plus platinum-based chemotherapy. The best therapeutic response achieved partial response (PR) and the progression-free survival was 6.4 months. At present, there is no standardized treatment for patients who got MET-secondary mutation combined with EGFR mutation after MET-TKI resistance. This report implied immunotherapy plus chemotherapy may be a good treatment option for such patients.