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表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)联合贝伐珠单抗治疗表皮生长因子受体(EGFR)突变型非小细胞肺癌(NSCLC)伴多发脑转移患者,较 EGFR-TKIs 单药治疗有生存获益。

EGFR-TKIs plus bevacizumab demonstrated survival benefit than EGFR-TKIs alone in patients with EGFR-mutant NSCLC and multiple brain metastases.

机构信息

Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China; Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Medical Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410006, China.

出版信息

Eur J Cancer. 2019 Nov;121:98-108. doi: 10.1016/j.ejca.2019.08.021. Epub 2019 Sep 27.

Abstract

INTRODUCTION

Previous studies suggested that epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKIs) plus bevacizumab could significantly prolong progression-free survival (PFS) than EGFR-TKI alone as first-line setting for patients with EGFR-mutant non-small-cell lung cancer (NSCLC). However, whether this combination could benefit patients with multiple brain metastases (BrMs) remains undetermined.

METHODS

A total of 208 patients with EGFR-mutant NSCLC and multiple BrM (number >3, at least one of lesions was measurable) were retrospectively identified. Kaplan-Meier curves with two-sided log-rank tests and Cox proportional hazards model with calculated hazard ratios and 95% confidence intervals were used to determine the survival difference.

RESULTS

Of all patients, 149 patients received EGFR-TKIs monotherapy and 59 received EGFR-TKIs plus bevacizumab as first-line setting. EGFR-TKIs plus bevacizumab was associated with a significantly higher intracranial objective response rate (ORR, 66.1% vs. 41.6%, P = 0.001), systemic ORR (74.6% vs. 57.1%, P = 0.019), longer intracranial PFS (14.0 vs. 8.2 months; P < 0.001) and systemic PFS (14.4 vs. 9.0 months; P < 0.001). Importantly, addition of bevacizumab also had a significantly longer overall survival (OS, 29.6 vs. 21.7 months; P < 0.001). Multivariate analysis consistently revealed that addition of bevacizumab was independently associated with prolonged intracranial and systemic PFS, and OS. No unexpected serious adverse effects were observed.

CONCLUSIONS

EGFR-TKIs plus bevacizumab prolonged not only PFS but also OS in patients with EGFR-mutant NSCLC and multiple BrMs when compared with EGFR-TKIs alone, indicating that this combination could be an alternative therapeutic option for those patients.

摘要

简介

先前的研究表明,表皮生长因子受体(EGFR)-酪氨酸激酶抑制剂(TKI)联合贝伐珠单抗作为 EGFR 突变型非小细胞肺癌(NSCLC)患者的一线治疗方案,相较于 EGFR-TKI 单药治疗,能显著延长无进展生存期(PFS)。然而,该联合方案是否能使伴有多发脑转移(BrM)的患者获益,目前仍未确定。

方法

本研究回顾性分析了 208 例伴有多发脑转移(脑转移灶数>3,至少有一个病灶可测量)的 EGFR 突变型 NSCLC 患者。采用双侧对数秩检验的 Kaplan-Meier 曲线和计算风险比和 95%置信区间的 Cox 比例风险模型来确定生存差异。

结果

所有患者中,149 例接受 EGFR-TKIs 单药治疗,59 例接受 EGFR-TKIs 联合贝伐珠单抗作为一线治疗。与 EGFR-TKIs 单药治疗相比,EGFR-TKIs 联合贝伐珠单抗治疗组的颅内客观缓解率(ORR,66.1% vs. 41.6%,P=0.001)、全身 ORR(74.6% vs. 57.1%,P=0.019)、颅内 PFS(14.0 个月 vs. 8.2 个月;P<0.001)和全身 PFS(14.4 个月 vs. 9.0 个月;P<0.001)均显著提高。此外,贝伐珠单抗的加入还显著延长了总生存期(OS,29.6 个月 vs. 21.7 个月;P<0.001)。多变量分析一致表明,贝伐珠单抗的加入与颅内和全身 PFS 和 OS 的延长独立相关。未观察到意外的严重不良事件。

结论

与 EGFR-TKIs 单药治疗相比,EGFR-TKIs 联合贝伐珠单抗不仅延长了 EGFR 突变型 NSCLC 伴多发脑转移患者的 PFS,而且延长了 OS,表明该联合方案可能是此类患者的一种治疗选择。

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