Division of Pulmonary and Critical Care Medicine, College of Medicine, Ewha Womans University, 1071 Anyangcheon-Ro, Yangcheon-gu, Seoul, 07985, Republic of Korea.
Division of Respiratory, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea.
BMC Cancer. 2021 Jan 11;21(1):52. doi: 10.1186/s12885-020-07765-6.
Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation types are associated with efficacy of EGFR TKIs. We investigated the clinical outcomes of afatinib, erlotinib, and gefitinib according to EGFR mutation type in patients with lung adenocarcinoma.
Between May 2010 and December 2018, we investigated 363 patients with advanced lung adenocarcinoma harboring EGFR mutations who received EGFR TKIs. Efficacies of EGFR TKIs such as response rate, progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated according to exon 19 deletion (E19del), L858R point mutation (L858R) and uncommon mutations.
The frequency of E19del was 48.2%, that of L858R was 42.4%, and that of uncommon mutations was 9.4%. E19del and L858R were associated with superior PFS and OS compared with uncommon mutations. Erlotinib showed significantly inferior OS than other TKIs (30.8 ± 3.3 in erlotinib vs. 39.1 ± 4.3 in afatinib vs. 48.4 ± 6.3 in gefitinib; p = 0.031) in patients with L858R. Gefitinib showed significantly inferior PFS (4.6 ± 1.1 in gefitinib vs. 11.6 ± 2.7 in afatinib vs. 10.6 ± 2.7 in erlotinib; p = 0.049) in patients with uncommon mutations.
Afatinib was significantly associated with a longer PFS, presenting constant effectiveness in all EGFR mutation types. Caution may be needed on the use of erlotinib for L858R and the use of gefitinib for uncommon EGFR mutations.
非小细胞肺癌中的表皮生长因子受体（EGFR）突变可预测对 EGFR 酪氨酸激酶抑制剂（TKI）的敏感性。EGFR 突变类型与 EGFR TKI 的疗效相关。我们根据肺腺癌患者的 EGFR 突变类型研究了阿法替尼、厄洛替尼和吉非替尼的临床结局。
在 2010 年 5 月至 2018 年 12 月期间，我们调查了 363 例接受 EGFR TKI 治疗的晚期肺腺癌患者，这些患者均存在 EGFR 突变。根据外显子 19 缺失（E19del）、L858R 点突变（L858R）和罕见突变，回顾性评估了 EGFR TKI 的疗效，如反应率、无进展生存期（PFS）和总生存期（OS）。
E19del 的频率为 48.2%，L858R 的频率为 42.4%，罕见突变的频率为 9.4%。与罕见突变相比，E19del 和 L858R 与更好的 PFS 和 OS 相关。与其他 TKI 相比，厄洛替尼的 OS 显著降低（厄洛替尼组为 30.8 ± 3.3 个月，阿法替尼组为 39.1 ± 4.3 个月，吉非替尼组为 48.4 ± 6.3 个月；p = 0.031）在 L858R 患者中。在罕见突变患者中，吉非替尼的 PFS 显著降低（吉非替尼组为 4.6 ± 1.1 个月，阿法替尼组为 11.6 ± 2.7 个月，厄洛替尼组为 10.6 ± 2.7 个月；p = 0.049）。
阿法替尼与更长的 PFS 显著相关，在所有 EGFR 突变类型中均表现出一致的疗效。在 L858R 患者中使用厄洛替尼和在罕见 EGFR 突变患者中使用吉非替尼时需要谨慎。
