Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has become a standardized treatment option for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC), but clinical findings of unavoidable primary or secondary resistance ultimately lead to disease progression. For this reason, finding markers for early prediction of effective populations and exploring optimized therapeutic regimens to prolong or reverse secondary resistance have become the focus of research at home and abroad.

To systematically evaluate the efficacy and safety of EGFR-TKI combined with chemotherapy for the first-line treatment of EGFR-mutated advanced non-small cell lung cancer based on data from domestic and international literature.

Three professionally recognized databases, PubMed, Embase, and Cochrane Library, were searched for randomized controlled trials eligible for the efficacy and safety of EGFR-TKI combination chemotherapy versus single-agent EGFR-TKI for the first-line treatment of patients with EGFR-mutated advanced non-small-cell lung cancer published from the time of construction to November 2023.Data on progression-free survival (PFS), overall survival (OS), objective remission rate (ORR), disease control rate (DCR), and grade≥3 adverse events were collected and analyzed by two investigators who independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. Subgroup analyses were performed based on baseline clinical characteristics, and data were statistically analyzed using RevMan 5.4.1.

Ten eligible studies with a total of 2 029 patients were included, including 1 049 patients in the experimental group of EGFR-TKI combined with standard chemotherapy; and 980 patients in the control group of EGFR-TKI alone. Meta-analysis showed that compared with EGFR-TKI monotherapy, EGFR-TKI combination chemotherapy prolonged PFS (HR=0.54, 95%CI=0.49-0.60, P<0.000 01) and OS (HR=0.69, 95%CI=0.59-0.79, P<0.000 01). Compared with EGFR-TKI monotherapy, EGFR-TKI combination chemotherapy improved ORR (OR=1.95, 95%CI=1.57-2.42, P<0.000 01) and DCR (OR=1.76, 95%CI=1.13-2.74, P=0.01) in patients with advanced NSCLC with EGFR mutations. In patients with concomitant brain metastases, EGFR-TKI combination chemotherapy prolonged PFS (HR=0.42, 95%CI=0.34-0.52, P<0.000 01) and OS (HR=0.69, 95%CI=0.51-0.94, P=0.02) in patients with EGFR-mutated advanced NSCLC compared with single-agent EGFR-TKI treatment.In patients without brain metastases at baseline, EGFR-TKI combination chemotherapy prolonged PFS compared with single-agent EGFR-TKI treatment in patients with advanced NSCLC with EGFR mutations (HR=0.62, 95%CI=0.53-0.72, P<0.000 01). The incidence of grade ≥3 adverse reactions was higher with EGFR-TKI combination chemotherapy than with single-agent EGFR-TKI treatment in patients with advanced NSCLC with EGFR mutations (OR=4.25, 95%CI=2.74-6.61, P<0.000 01). The incidence of grade ≥3 adverse reactions was higher in the combination therapy group than in the monotherapy group.

EGFR-TKI combination chemotherapy significantly prolongs first-line PFS and OS in EGFR-mutated advanced non-small cell lung cancer, especially in patients with baseline brain metastases. The incidence of adverse events was increased in the combination therapy group, particularly the incidence of grade ≥3 hematologic toxicity, but was overall safe and manageable.

表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）的靶向治疗已成为表皮生长因子受体（EGFR）突变晚期非小细胞肺癌（NSCLC）的规范治疗方案，但临床发现了不可避免的原发性或继发性耐药最终导致了疾病进展。为此，寻找早期预测有效人群的标志物和探索延长或逆转继发性耐药的优化治疗方案成为国内外研究重点。

依据国内外文献数据系统评价EGFR-TKI联合化疗一线治疗EGFR突变晚期NSCLC的疗效及安全性。

计算机检索PubMed、Embase、Cochrane Library数据库发布的有关EGFR-TKI联合化疗对比单药EGFR-TKI一线治疗EGFR突变晚期NSCLC患者疗效及安全性的随机对照试验，检索时间为建库至2023年11月。由2名研究者独立筛选文献、提取数据并评价纳入研究的偏倚风险，对无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）以及≥3级不良反应等数据收集和分析。基于基线临床特征进行亚组分析，使用RevMan 5.4.1版本进行数据统计分析。

纳入符合条件的10项研究，共2 029例患者，其中EGFR-TKI联合化疗组1 049例患者，单纯EGFR-TKI组980例患者。Meta分析结果显示，与单纯EGFR-TKI组相比，EGFR-TKI联合化疗组可延长EGFR突变晚期NSCLC患者的PFS（HR=0.54，95%CI=0.49~0.60，P<0.000 01）和OS（HR=0.69，95%CI=0.59~0.79，P<0.000 01）。与单纯EGFR-TKI组相比，EGFR-TKI联合化疗组可提高EGFR突变晚期NSCLC患者的ORR（OR=1.95，95%CI=1.57~2.42，P<0.000 01）和DCR（OR=1.76，95%CI=1.13~2.74，P=0.01）。在伴随脑转移的患者中，与单纯EGFR-TKI治疗相比，EGFR-TKI联合化疗延长EGFR突变晚期NSCLC患者的PFS（HR=0.42，95%CI=0.34~0.52，P<0.000 01）和OS（HR=0.69，95%CI=0.51~0.94，P=0.02）。在基线无脑转移的患者中，与单纯EGFR-TKI治疗相比，EGFR-TKI联合化疗延长EGFR突变晚期NSCLC患者的PFS（HR=0.62，95%CI=0.53~0.72，P<0.000 01）。EGFR-TKI联合化疗治疗EGFR突变晚期NSCLC患者的≥3级不良反应发生率高于单纯EGFR-TKI治疗（OR=4.25，95%CI=2.74~6.61，P<0.000 01）。

EGFR-TKI联合化疗可显著延长EGFR突变晚期NSCLC患者的一线PFS及OS，尤其是基线脑转移患者；但不良反应发生率增加，尤其是≥3级血液学相关毒副作用发生率，整体是安全可控的。