Although dual anti-HER2 therapy, namely, pertuzumab plus trastuzumab, has shown promising results in patients with HER2-positive breast cancer (BC), it is still unclear whether dual therapy will increase adverse effects (AEs) while ensuring the efficacy compared with trastuzumab monotherapy. We conducted a systematic review and meta-analysis to compare the efficacy and safety of combined therapy with monotherapy.

A systematic search was performed to identify eligible randomized controlled trials (RCTs) that evaluated the administration of dual anti-HER2 therapy [pertuzumab plus trastuzumab or trastuzumab emtansine (T-DM1)] versus monotherapy (trastuzumab or T-DM1). The primary endpoints were overall survival (OS) and progression-free survival (PFS).

Fourteen RCTs (8,378 patients) were identified. Compared to monotherapy, dual therapy significantly improved the OS (HR = 0.77, 95% CI: 0.59–0.99) and PFS (HR = 0.74, 95% CI: 0.63–0.86) in advanced BC. In neoadjuvant therapy, dual blockade has a higher ORR rate than monotherapy. Grade 3 or higher febrile neutropenia, diarrhea, and anemia as well as heart failure were more frequently reported in dual therapy compared to monotherapy. No significant difference in serious AEs was observed between the two groups. In the subgroup analysis, compared to single-target therapy, dual-target therapy has higher OS and PFS rates in Asian patients with advanced therapy; however, total grade ≥3 AEs and serious AEs were significantly higher in the dual group in Asian patients.

Our study confirms that the combination of pertuzumab and trastuzumab therapy could substantially improve the outcome of patients with HER2-positive breast cancer and was well tolerated compared to trastuzumab monotherapy.

尽管帕妥珠单抗加曲妥珠单抗双重抗HER2疗法在HER2阳性乳腺癌（BC）患者中显示出可喜的结果，但与曲妥珠单抗相比，双重疗法是否会在确保疗效的同时增加不良反应（AEs）尚不清楚单药治疗。我们进行了系统评价和荟萃分析，以比较联合治疗与单一治疗的疗效和安全性。

进行了系统检索，以确定评估双重抗 HER2 治疗 [帕妥珠单抗加曲妥珠单抗或曲妥珠单抗 emtansine (T-DM1)] 与单一疗法（曲妥珠单抗或 T-DM1）的管理的合格随机对照试验 (RCT)。主要终点是总生存期（OS）和无进展生存期（PFS）。

确定了 14 项 RCT（8,378 名患者）。与单一疗法相比，双联疗法显着改善了晚期 BC 的 OS（HR = 0.77, 95% CI: 0.59–0.99）和 PFS（HR = 0.74, 95% CI: 0.63–0.86）。在新辅助治疗中，双重阻断的 ORR 率高于单一疗法。与单药治疗相比，双药治疗更常报告 3 级或更高的发热性中性粒细胞减少、腹泻和贫血以及心力衰竭。两组之间在严重 AE 方面未观察到显着差异。在亚组分析中，与单靶点治疗相比，双靶点治疗在亚洲晚期治疗患者中具有更高的 OS 和 PFS 率；然而，在亚洲患者的双重组中，总 ≥3 级 AE 和严重 AE 显着更高。

我们的研究证实，帕妥珠单抗和曲妥珠单抗联合治疗可以显着改善 HER2 阳性乳腺癌患者的预后，并且与曲妥珠单抗单药治疗相比具有良好的耐受性。