Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
Department of Genetic Oncology, Osaka International Cancer Institute, Osaka, Japan.
Invest New Drugs. 2022 Oct;40(5):1137-1140. doi: 10.1007/s10637-022-01264-0. Epub 2022 Jun 3.
It has been reported that the efficacy of EGFR-TKI is predicted, not by which exon of the EGFR gene is mutated, but by the structural change in the EGFR protein due to the mutation. Here, we present an EGFR-mutated lung cancer patient with a 13-year history of anticancer treatment, in which EGFR ex.19 deletion (E746_S752 > V) and G724S mutations were detected by liquid biopsy during 12th line afatinib treatment, and switching to dacomitinib showed improvement of cancerous meningitis. We choose dacomitinib as 14th line chemotherapy based on ex.19 deletion and G724S mutant EGFR structure and its penetration rate to cerebral fluid, which successfully prolonged her life by 6 months. The optimal EGFR-TKI may be selected by understanding the EGFR compound mutation profile by next generation sequencing and predicting the effect based on the structure. Dacomitinib may be effective choice in afatinib-refractory carcinomatous meningitis harboring G724S mutation. This is the first case report showing that a change to dacomitinib responded to afatinib refractory cancerous meningitis.
据报道，EGFR-TKI 的疗效不是由 EGFR 基因的哪个外显子发生突变决定的，而是由突变导致的 EGFR 蛋白的结构变化决定的。在这里，我们报告了一例 EGFR 突变型肺癌患者，该患者在接受第 12 线阿法替尼治疗期间通过液体活检检测到 EGFR ex.19 缺失（E746_S752>>V）和 G724S 突变，并且在切换至达可替尼后癌性脑膜炎得到改善。我们根据 ex.19 缺失和 G724S 突变型 EGFR 结构及其对脑脊液的穿透率选择达可替尼作为第 14 线化疗药物，这成功地将她的生命延长了 6 个月。通过下一代测序了解 EGFR 复合突变谱，并根据结构预测疗效，可能会选择最佳的 EGFR-TKI。对于阿法替尼难治性癌性脑膜炎伴 G724S 突变的患者，达可替尼可能是一种有效的选择。这是首例报告显示，改用达可替尼可对阿法替尼难治性癌性脑膜炎产生应答。
