Thoracic Oncology Ward, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Cancer Sci. 2023 Jun;114(6):2552-2559. doi: 10.1111/cas.15769. Epub 2023 Mar 12.
Differently from epidermal growth factor receptor (EGFR) 19Del and L858R mutations, the panoramic description of uncommon EGFR mutations is far from mature. Our understanding of its population characteristics, treatment response, and drug resistance mechanisms needs urgent expansion and deepening. Our study enrolled 437 patients with non-small-cell lung cancer from four clinical centers and who had uncommon EGFR mutations. The clinical characteristics of all patients and the treatment outcomes of 190 advanced patients who received pharmacotherapy were analyzed. Moreover, the acquired resistance mechanisms were explored based on 53 tissue or liquid re-biopsy data in 45 patients. Patients with EGFR 20ins had a shorter survival time compared with patients with non-20ins mutations. In total, 149 cases had received EGFR-tyrosine kinase inhibitors (TKI); afatinib was significantly superior to other EGFR-TKIs both in ORR and mPFS in all uncommon mutations and especially in the L861Q group. The most common acquired drug resistance mechanism was MET amplification, followed by EGFR T790M, which was significantly different from common EGFR mutations.
与表皮生长因子受体（EGFR）19Del 和 L858R 突变不同，罕见 EGFR 突变的全面描述远未成熟。我们对其人群特征、治疗反应和耐药机制的认识亟待扩展和深化。本研究纳入了来自四个临床中心的 437 名非小细胞肺癌患者，这些患者均存在罕见的 EGFR 突变。分析了所有患者的临床特征和 190 名接受药物治疗的晚期患者的治疗结果。此外，还基于 45 名患者的 53 份组织或液体再活检数据探索了获得性耐药机制。与非 20ins 突变患者相比，EGFR 20ins 患者的生存时间更短。共有 149 例接受了 EGFR 酪氨酸激酶抑制剂（TKI）治疗；阿法替尼在所有罕见突变（尤其是 L861Q 组）中的 ORR 和 mPFS 方面均明显优于其他 EGFR-TKI。最常见的获得性耐药机制是 MET 扩增，其次是 EGFR T790M，与常见 EGFR 突变明显不同。
