Liu Xiaoqun, Liu Xiangdong, Qiao Tiankui, Chen Wei, Yuan Sujuan
Department of Oncology.
Department of Ophthalmology, Affiliated Jinshan Hospital, Fudan University, Shanghai, People's Republic of China.
Onco Targets Ther. 2016 Jun 30;9:3771-81. doi: 10.2147/OTT.S103954. eCollection 2016.
The combined therapy of bevacizumab (BEV) with taxane (paclitaxel or docetaxel) has shown an improvement on progression-free survival (PFS) and objective remission in Her2-negative patients with locally recurrent or metastatic breast cancer (LR/MBC). However, there was no benefit in overall survival (OS). The aim of this study was to evaluate the efficacy and safety of adding an agent to the BEV/taxane regimens for the treatment of Her2-negative patients with LR/MBC in a first-line setting.
We searched PubMed, Web of Science, EMBASE, EBSCO, and the Cochrane Library databases for eligible trials. A meta-analysis was performed using Review Manager 5.0 freeware package. We calculated the hazard ratio (HR) for PFS and OS. The odds ratio (OR) was used to calculate objective response rate (ORR) and grade 3/4 drug-related adverse events. The heterogeneity of study outcomes was calculated by the χ (2) test or I (2) statistics.
A total of 1,124 patients from seven randomized controlled trials were analyzed. Our meta-analysis showed that the ORR was significantly improved in the BEV/taxane-based triplet group when compared with the BEV/taxane-based doublet group (OR =1.31, 95% confidence interval [CI]: 1.03-1.67, P=0.03). A subset analysis showed that a similar result was achieved in the triplet group in which a cytotoxic agent was added (OR =1.46, 95% CI: 1.09-1.95, P=0.01). However, the PFS and OS had no statistically significant differences between the two groups (HR =0.87, 95% CI: 0.68-1.13, P=0.31; HR =0.98, 95% CI: 0.82-1.16, P=0.78, respectively). Regarding safety, thromboembolic events, fatigue, and diarrhea (all $grade 3) were more frequently observed in the BEV/taxane-based triplet group (OR =3.8, 95% CI: 1.86-7.79, P=0.0003; OR =1.55, 95% CI: 1.05-2.27, P=0.03; OR =2.1, 95% CI: 1.29-3.41, P=0.003, respectively). Other toxic effects had no statistically significant differences between the two groups.
Our results showed that adding an agent to BEV/taxane treatment regimens did not significantly improve PFS and prolong OS, except for conferring a significant advantage toward improved ORR in the first-line therapy for Her2-negative patients with LR/MBC. However, its side effects are predictable and manageable.
贝伐单抗（BEV）与紫杉烷类（紫杉醇或多西他赛）联合治疗在人表皮生长因子受体2（Her2）阴性的局部复发或转移性乳腺癌（LR/MBC）患者中显示出无进展生存期（PFS）的改善和客观缓解。然而，总生存期（OS）并无获益。本研究旨在评估在一线治疗中，在BEV/紫杉烷方案基础上加用一种药物治疗Her2阴性LR/MBC患者的疗效和安全性。
我们检索了PubMed、科学网、EMBASE、EBSCO和Cochrane图书馆数据库以获取符合条件的试验。使用Review Manager 5.0免费软件包进行荟萃分析。我们计算了PFS和OS的风险比（HR）。比值比（OR）用于计算客观缓解率（ORR）和3/4级药物相关不良事件。研究结果的异质性通过χ²检验或I²统计量计算。
共分析了来自7项随机对照试验的1124例患者。我们的荟萃分析表明，与基于BEV/紫杉烷的双联组相比，基于BEV/紫杉烷的三联组的ORR显著提高（OR = 1.31，95%置信区间[CI]：1.03 - 1.67，P = 0.03）。亚组分析显示，在加用细胞毒性药物的三联组中也得到了类似结果（OR = 1.46，95% CI：1.09 - 1.95，P = 0.01）。然而，两组之间的PFS和OS无统计学显著差异（HR = 0.87，95% CI：0.68 - 1.13，P = 0.31；HR = 0.98，95% CI：0.82 - 1.16，P = 0.78）。关于安全性，基于BEV/紫杉烷的三联组更频繁地观察到血栓栓塞事件、疲劳和腹泻（均为3级）（OR = 3.8，95% CI：1.86 - 7.79，P = 0.0003；OR = 1.55，95% CI：1.05 - 2.27，P = 0.03；OR = 2.1，95% CI：1.29 - 3.41，P = 0.003）。两组之间其他毒性作用无统计学显著差异。
我们的结果表明，在BEV/紫杉烷治疗方案基础上加用一种药物除了在Her2阴性LR/MBC患者的一线治疗中对提高ORR有显著优势外，并未显著改善PFS和延长OS时间。然而，其副作用是可预测和可控制的。
