低剂量阿帕替尼联合新辅助化疗治疗早期三阴性乳腺癌（《柳叶刀》）：一项单中心、单臂、II期试验
Low-dose apatinib combined with neoadjuvant chemotherapy in the treatment of early-stage triple-negative breast cancer (LANCET): a single-center, single-arm, phase II trial.
作者信息
Yang Ciqiu, Zhang Junsheng, Zhang Yi, Ji Fei, Chen Yitian, Zhu Teng, Zhang Liulu, Gao Hongfei, Yang Mei, Li Jieqing, Cheng Minyi, Wang Kun
机构信息
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No. 123 Huifu West Road, Guangzhou, 510080, China.
出版信息
Ther Adv Med Oncol. 2022 Aug 12;14:17588359221118053. doi: 10.1177/17588359221118053. eCollection 2022.
BACKGROUND
Antiangiogenic therapy combined with chemotherapy could improve pathological complete response (pCR) for breast cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2. We assessed the efficacy and safety of apatinib combined with standard neoadjuvant chemotherapy in patients with triple-negative breast cancer (TNBC).
MATERIALS AND METHODS
This single-arm, phase II study enrolled patients aged 18-70 years with previously untreated stage IIA-IIIB TNBC. Patients received oral apatinib at a dose of 250 mg once daily and intravenously docetaxel every 3 weeks for four cycles, followed by epirubicin plus cyclophosphamide every 3 weeks for four cycles. The primary endpoint was the pCR rate in the breast and lymph nodes. Secondary endpoints included objective response rate, event-free survival (EFS), overall survival (OS), and safety.
RESULTS
In all, 31 patients were enrolled, and the median follow-up time was 22.9 months (range: 10.1-41.6 months). The pCRs in both breast and lymph nodes were achieved in 17 [54.8%; 95% confidence interval (CI): 36.0-72.7] of 31 patients. Objective responses were achieved in 29 patients (93.5%; 95% CI: 78.6-99.2), and disease control was achieved in 31 patients (100%; 95% CI: 88.8-100.0). The 2-year EFS and 2-year OS were 90.9% and 94.4%, respectively. The five most common treatment-related adverse events were fatigue (51%), hypertension (41%), anorexia (39%), hand-foot syndrome (35%), and diarrhea (32%). Few grade 3 or more adverse events were observed.
CONCLUSION
The combination of apatinib with docetaxel followed by epirubicin plus cyclophosphamide showed excellent efficacy and manageable toxicities; and further randomized controlled phase III trials are warranted.
TRIAL REGISTRATION
This trial was registered with ClinicalTrials.gov (NCT03243838) on 5 August 2017.
背景
抗血管生成疗法联合化疗可提高乳腺癌的病理完全缓解率（pCR）。阿帕替尼是一种口服酪氨酸激酶抑制剂，可选择性抑制血管内皮生长因子受体2。我们评估了阿帕替尼联合标准新辅助化疗治疗三阴性乳腺癌（TNBC）患者的疗效和安全性。
材料与方法
这项单臂II期研究纳入了年龄在18至70岁之间、先前未接受过治疗的IIA-IIIB期TNBC患者。患者接受口服阿帕替尼，剂量为每日一次250mg，每3周静脉注射多西他赛一次，共四个周期，随后每3周静脉注射表柔比星加环磷酰胺一次，共四个周期。主要终点是乳腺和淋巴结的pCR率。次要终点包括客观缓解率、无事件生存期（EFS）、总生存期（OS）和安全性。
结果
总共纳入了31例患者，中位随访时间为22.9个月（范围：10.1-41.6个月）。31例患者中有17例（54.8%；95%置信区间（CI）：36.0-72.7）实现了乳腺和淋巴结的pCR。29例患者（93.5%；95%CI：78.6-99.2）获得了客观缓解，31例患者（100%；95%CI：88.8-100.0）实现了疾病控制。2年EFS和2年OS分别为90.9%和94.4%。五种最常见的治疗相关不良事件为疲劳（51%）、高血压（41%）、厌食（39%）、手足综合征（35%）和腹泻（32%）。观察到的3级或更高级别不良事件很少。
结论
阿帕替尼联合多西他赛，随后使用表柔比星加环磷酰胺显示出优异的疗效和可控的毒性；有必要进一步开展随机对照III期试验。
试验注册
本试验于2017年8月5日在ClinicalTrials.gov（NCT03243838）注册。
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