表皮生长因子受体（EGFR）阳性的脑转移非小细胞肺癌患者在EGFR酪氨酸激酶抑制剂基础上加用化疗的获益与风险：一项基于随机对照试验的荟萃分析

The benefit and risk of addition of chemotherapy to EGFR tyrosine kinase inhibitors for EGFR-positive non-small cell lung cancer patients with brain metastases: a meta-analysis based on randomized controlled trials.

作者信息

Chen Zhigang, Fu Xiang, Zhu Lingping, Wen Xiurong, Zhang Shihao

机构信息

Department of Oncology, Shangrao People's Hospital, Shangrao, China.

Department of Respiratory and Critical Care Medicine, Ganzhou People's Hospital, Ganzhou, China.

出版信息

Front Oncol. 2024 Oct 21;14:1448336. doi: 10.3389/fonc.2024.1448336. eCollection 2024.

BACKGROUND

Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with chemotherapy (ETC) offers more advantages for patients with EGFR-positive non-small cell lung cancer (NSCLC) than using EGFR TKIs alone (ET). However, whether this conclusion applies to patients with brain metastases (BM) remains controversial. This meta-analysis was performed to evaluate the benefits and risks of the two groups.

METHODS

Six databases were systematically searched for relevant literatures comparing ETC versus ET in treating EGFR-positive NSCLC patients with BM. The primary outcome assessed was overall survival (OS), while secondary outcomes included progression-free survival (PFS), and central nervous system (CNS)-PFS, responses, progression status and safety.

RESULTS

Seven studies based on five randomized clinical trials with 550 patients were included. The ETC group exhibited better OS (hazard ratio [HR]: 0.64 [0.48, 0.87]), PFS (HR: 0.42 [0.34, 0.52]), and CNS-PFS (HR: 0.42 [0.31, 0.57]). The benefits in survival for OS, PFS, and CNS-PFS were validated in nearly all subgroups. Meanwhile, the overall objective response rate (ORR) (risk ratio [RR]: 1.25 [1.02, 1.52]) and CNS-ORR (RR: 1.19 [0.93, 1.51]) also tended to favor the ETC group. However, the addition of chemotherapy also brought about more grade 3-5/serious adverse events (AEs). The top five grade 3-5 AEs in the ETC group were alanine aminotransferase increase (11.25%), neutropenia (7.5%), nausea (7.5%), anorexia (5%), and diarrhea (5%).

CONCLUSIONS

ETC appears to be better than ET in treating EGFR-positive NSCLC patients with BM, with better OS, PFS, CNS-PFS, and responses. However, its poorer safety profile also needs to be taken into consideration.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024551073.

背景

对于表皮生长因子受体（EGFR）阳性的非小细胞肺癌（NSCLC）患者，将表皮生长因子受体酪氨酸激酶抑制剂（TKIs）与化疗（ETC）联合使用比单独使用EGFR TKIs（ET）具有更多优势。然而，这一结论是否适用于脑转移（BM）患者仍存在争议。本荟萃分析旨在评估两组的获益和风险。

方法

系统检索六个数据库，以查找比较ETC与ET治疗EGFR阳性NSCLC合并BM患者的相关文献。评估的主要结局是总生存期（OS），次要结局包括无进展生存期（PFS）、中枢神经系统（CNS）-PFS、缓解率、疾病进展状态和安全性。

结果

纳入了基于五项随机临床试验的七项研究，共550例患者。ETC组的OS（风险比[HR]：0.64[0.48，0.87]）、PFS（HR：0.42[0.34，0.52]）和CNS-PFS（HR：0.42[0.31，0.57]）表现更好。OS、PFS和CNS-PFS在几乎所有亚组中均证实了生存获益。同时，总体客观缓解率（ORR）（风险比[RR]：1.25[1.02，1.52]）和CNS-ORR（RR：1.19[0.93，1.51]）也倾向于ETC组。然而，添加化疗也带来了更多3-5级/严重不良事件（AE）。ETC组中排名前五的3-5级AE为谷丙转氨酶升高（11.25%）、中性粒细胞减少（7.5%）、恶心（7.5%）、食欲减退（5%）和腹泻（5%）。