Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the current recommended option for the first-line treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC). Resistance to first-generation TKIs led to the development of second- and third-generation TKIs with improved clinical outcomes. However, sequential administration of TKIs has led to the emergence of new EGFR resistance mutations and persistent tumor cell survival. This evidence highlights the potential role of EGFR in transducing growth signals in NSCLC tumor cells. Therefore, dual inhibition of EGFR using combinations of anti-EGFR monoclonal antibodies (mAbs) and EGFR-TKIs may offer a unique treatment strategy to suppress tumor cell growth. Several clinical studies have demonstrated the benefits of dual blockade of EGFR using anti-EGFR mAbs coupled with EGFR-TKIs in overcoming treatment resistance in patients with EGFR-mutated NSCLC. However, a single treatment option may not result in the same clinical benefits in all patients with acquired resistance. Biomarkers, including EGFR overexpression, EGFR gene copy number, EGFR and KRAS mutations, and circulating tumor DNA, have been associated with improved clinical efficacy with anti-EGFR mAbs in patients with NSCLC and acquired resistance. Further investigation of biomarkers may allow patient selection for those who could benefit from anti-EGFR mAbs in combination with EGFR-TKIs. This review summarizes findings of recent studies of anti-EGFR mAbs in combination with EGFR-TKIs for the treatment of patients with EGFR-mutated NSCLC, as well as clinical evidence for potential biomarkers towards personalized targeted medicine.

表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）是目前推荐用于 EGFR 突变非小细胞肺癌（NSCLC）患者一线治疗的选择。对第一代 TKI 的耐药性导致了第二代和第三代 TKI 的开发，并改善了临床结果。然而，TKI 的连续给药导致了新的 EGFR 耐药突变的出现和肿瘤细胞的持续存活。这一证据强调了 EGFR 在 NSCLC 肿瘤细胞中转导生长信号中的潜在作用。因此，使用抗 EGFR 单克隆抗体 (mAb) 和 EGFR-TKI 组合双重抑制 EGFR 可能提供一种独特的治疗策略来抑制肿瘤细胞生长。多项临床研究已经证明，使用抗 EGFR mAb 与 EGFR-TKI 联合使用双重阻断 EGFR 可以帮助克服 EGFR 突变 NSCLC 患者的治疗耐药性。然而，单一治疗选择可能不会对所有获得性耐药患者产生相同的临床益处。生物标志物，包括 EGFR 过表达、EGFR基因拷贝数、EGFR和KRAS突变以及循环肿瘤 DNA，与抗 EGFR 单克隆抗体在 NSCLC 和获得性耐药患者中改善的临床疗效相关。生物标志物的进一步研究可能允许患者选择那些可以受益于抗 EGFR mAb 与 EGFR-TKI 组合的患者。本综述总结了抗 EGFR 单克隆抗体与 EGFR-TKI 联合治疗 EGFR 突变 NSCLC 患者的最新研究结果，以及个性化靶向药物潜在生物标志物的临床证据。