Catalan Institue of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
Ann N Y Acad Sci. 2010 Oct;1210:45-52. doi: 10.1111/j.1749-6632.2010.05775.x.
Activating mutations in the form of deletions in exon 19 (del 19) or the missense mutation L858R in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) predict outcome to use of EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. Pooled data from several phase II studies show that gefitinib and erlotinib induce responses in over 70% of NSCLC patients harboring EGFR mutations, with progression-free survival (PFS) ranging from 9 to 13 months. Two studies in Caucasian and Asian patients have confirmed that these subgroups of patients attain PFS up to 14 months. These landmark outcomes have been accompanied by new challenges, primarily the additional role of chemotherapy and the management of tumors with the secondary T790M mutation that confers resistance to EGFR TKIs. Mechanisms of resistance to reversible EGFR TKIs should be further clarified and could be related to modifications in DNA repair.
表皮生长因子受体（EGFR）酪氨酸激酶结构域中外显子 19 缺失（del19）或错义突变 L858R 的激活突变可预测 EGFR 酪氨酸激酶抑制剂（TKI）的疗效，如吉非替尼和厄洛替尼。几项 II 期研究的汇总数据显示，吉非替尼和厄洛替尼诱导携带 EGFR 突变的 NSCLC 患者的反应率超过 70%，无进展生存期（PFS）为 9 至 13 个月。在白人和亚洲患者中进行的两项研究证实，这些亚组患者的 PFS 可达到 14 个月。这些里程碑式的结果带来了新的挑战，主要是化疗的附加作用，以及管理继发性 T790M 突变的肿瘤，该突变导致对 EGFR TKI 的耐药性。对可逆 EGFR TKI 的耐药机制尚需进一步阐明，可能与 DNA 修复的改变有关。
