难治型晚期乳腺癌阿帕替尼真实疗效
对于多线治疗失败且对化疗耐药的晚期乳腺癌患者，由于缺乏标准治疗方案，选择合适治疗方法成为一个相当大的挑战。由于血管内皮生长因子VEGF及其受体VEGFR2与肿瘤的生长和转移密切相关，而且E2100、RIBBON-1、BO17708、N063H等随机对照三期临床研究已经证实，抗VEGF药物贝伐珠单抗可提高某些晚期乳腺癌一线或二线化疗的无进展生存率，这些证据表明抗血管生成药物可能对某些晚期乳腺癌患者有效。中国原创VEGFR2抑制剂阿帕替尼已被推荐用于晚期胃癌或胃食管交界处腺癌、肝癌、子宫颈癌、肺癌。既往二期临床研究也已证实阿帕替尼单药治疗晚期难治型三阴性乳腺癌患者的有效性和安全性。不过，关于阿帕替尼对晚期乳腺癌患者有效性和安全性的真实世界研究极少且样本量较小，故有必要在真实世界环境中更准确地评价阿帕替尼对晚期乳腺癌患者的作用。
2021年6月，瑞士《肿瘤学前沿》在线发表中国山东省肿瘤医院、山东省肿瘤防治研究院、山东大学齐鲁医学院、山东第一医科大学、山东省医学科学院、中国工程院院士于金明等学者的研究报告，在真实世界环境中评价了阿帕替尼对晚期乳腺癌多线治疗失败患者的安全性和有效性。
该单中心回顾研究对2015年9月～2019年8月在山东省肿瘤医院开始阿帕替尼治疗的66例晚期乳腺癌多线治疗失败患者进行回顾分析。主要终点包括无进展生存和总生存，次要终点包括治疗相关毒性。
结果发现，中位无进展生存和中位总生存分别为6.0个月和10.0个月。临床获益率为40.9%。全部患者对治疗的耐受性良好，无一例患者死于毒性反应。阿帕替尼的常见毒性为手足综合征、继发高血压、疲劳。既往化疗方案数量与无病生存和总生存显著相关。卡培他滨可能是较好的联合用药选择，中位总生存达19个月，而阿帕替尼联合其他药物为9个月，阿帕替尼单药治疗为10个月。
因此，该单中心小样本回顾研究结果表明，阿帕替尼对晚期乳腺癌多线治疗失败患者仍然有效，未见显著治疗相关不良事件，可能成为多线化疗失败女性维持挽救治疗选择之一，故有必要进一步开展多中心大样本随机对照前瞻研究进行验证。
Front Oncol. 2021 Jun;11:643654.
Real-World Data on Apatinib Efficacy - Results of a Retrospective Study in Metastatic Breast Cancer Patients Pretreated With Multiline Treatment.
Liu Z, Shan J, Yu Q, Wang X, Song X, Wang F, Li C, Yu Z, Yu J.
Shandong Cancer Hospital and Institute, Cheeloo College of Medicine, Shandong University, Jinan, China; Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China; Cleveland Clinic, Cleveland, OH, United States.
OBJECTIVES: The NCCN guidelines recommend that the addition of bevacizumab should be considered in metastatic breast cancers in some circumstances, but there are no recommendations for the similar antiangiogenic drug apatinib. The aim of this study was to evaluate the safety and efficacy of apatinib in metastatic breast cancer patients pretreated with multiline treatment in a real-world setting.
MATERIALS AND METHODS: Metastatic breast cancer patients pretreated with multiline treatment who had apatinib treatment initiated from September 2015 to August 2019 at Shandong Cancer Hospital and Institute were included. The primary endpoints included PFS and OS, and the secondary endpoint was treatment-related toxicity.
RESULTS: A total of 66 patients with metastatic breast cancer received apatinib treatment after failure of multiline chemotherapy in this study. The median PFS and OS of all 66 patients were 6.0 months and 10.0 months, respectively. The clinical beneficial rate was 40.9%. All patients tolerated treatment well, and no patients died of toxicity. The common toxicities of apatinib were hand and foot syndrome, secondary hypertension and fatigue events. The number of prior chemotherapy regimens was significantly associated with DFS and OS. Capecitabine may be a better choice for combination with a longer median OS of 19 months, while apatinib combined with other drugs was 9 months, and the apatinib monotherapy was 10 months.
CONCLUSION: Apatinib produced moderate efficacy in metastatic breast cancer patients pretreated with multiline treatment with no significant treatment-related adverse events. Apatinib might be a choice for women as a maintenance salvage therapy following multiline chemotherapy failure.
KEYWORDS: apatinib; breast cancer; efficacy; metastatic; safety
PMID: 34178630
PMCID: PMC8224527
DOI: 10.3389/fonc.2021.643654