一线 EGFR-TKIs 联合抗血管生成抑制剂在晚期 EGFR 突变型非小细胞肺癌中的合理应用：系统评价和荟萃分析。

Rational Application of First-Line EGFR-TKIs Combined with Antiangiogenic Inhibitors in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

机构信息

Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China.

出版信息

Biomed Res Int. 2021 Jan 28;2021:8850256. doi: 10.1155/2021/8850256. eCollection 2021.

PURPOSE

A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with antiangiogenic inhibitors (A + T) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC).

METHODS

PubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade ≥ 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs).

RESULTS

Data were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone (HR = 0.60; < 0.01) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A + T and TKI alone groups (HR = 0.933; = 0.551) regardless of EGFR mutation type. The ORR for A + T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups (RR = 0.774; = 0.008). There was no difference in the positive rates of acquired T790M mutation between the two groups (RR = 0.967; = 0.846). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A + T group (RR = 0.881; = 0.002).

CONCLUSION

Addition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.

目的

对随机对照试验（RCT）进行荟萃分析，以比较表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）联合抗血管生成抑制剂（A + T）与 EGFR-TKI 单药治疗初治晚期 EGFR 突变型非小细胞肺癌（NSCLC）患者的疗效和安全性差异。

方法

检索 PubMed、Embase、Web of Science 和 Cochrane 电子数据库，以查找相关 RCT。还对会议摘要进行了审查，以确定合适的研究。终点包括无进展生存期（PFS）、总生存期（OS）、1 年和 2 年 OS 率、客观缓解率（ORR）和≥3 级不良事件。所有汇总结果均使用风险比（HRs）或相对风险比（RRs）表示。

结果

从六项符合条件的 RCT 中收集数据，共纳入 1244 名参与者（A + T 组 619 名，TKI 单药组 625 名）。A + T 组与 TKI 单药组相比，PFS 显著改善（HR = 0.60；<0.01），无论 EGFR 突变类型（外显子 19 缺失或 L858R）和脑转移状态（有无脑转移）如何。A + T 联合治疗组与 TKI 单药组的中位 OS 无显著差异（HR = 0.933；= 0.551），无论 EGFR 突变类型如何。在exon 19 缺失亚组中，A + T 联合治疗组的 ORR 明显高于 TKI 单药组（RR = 0.774；= 0.008）。两组获得性 T790M 突变的阳性率无差异（RR = 0.967；= 0.846）。TKI 单药组的患者比 A + T 组的患者接受了更多种后续系统治疗（RR = 0.881；= 0.002）。