Zhu Anjie, Yuan Peng, Hu Nanlin, Li Mingzhou, Wang Wenmiao, Wang Xue, Yue Jian, Wang Jiayu, Luo Yang, Ma Fei, Zhang Pin, Li Qing, Xu Binghe, Cao Shanbo, Lippi Giuseppe, Naito Yoichi, Osman Mohammed A, Marta Gustavo N, Franceschini Gianluca, Orlandi Armando
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Cancer Biol Med. 2021 May 26;18(3):875-87. doi: 10.20892/j.issn.2095-3941.2020.0418.
Apatinib is an oral TKI targeting VEGFR-2. Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated mBC. Oral vinorelbine also holds promise as a treatment of choice in patients with mBC. This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated mBC. In addition, we detected gene variants in ctDNA to explore the therapeutic implications.
This study enrolled patients with HER2-negative mBC who were pretreated with anthracycline/taxanes. Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m on days 1, 8, and 15 of every cycle (3 weeks). The primary endpoint was PFS. The secondary endpoints were ORR, CBR, OS, and safety. Patients eligible for ctDNA detection were evaluated before and during treatment.
Forty patients were enrolled. The median PFS was 5.2 months (95% CI, 3.4-7.0 months), and the median OS was 17.4 months (95% CI, 8.0-27.0 months). The ORR was 17.1% (6/35), and the CBR was 45.7% (16/35). The most common AEs included gastrointestinal reaction, myelosuppression, and hypertension. In 20 patients, ctDNA was detected at baseline and during treatment. A significant difference was found in PFS for undetected detected baseline ctDNA (13.9 months 3.6 months, = 0.018).
All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative mBC, with acceptable and manageable toxicity profiles. Patients with no gene variant detected and lower variant allele frequencies in ctDNA at baseline showed longer PFS.
阿帕替尼是一种靶向血管内皮生长因子受体2（VEGFR-2）的口服酪氨酸激酶抑制剂（TKI）。单药阿帕替尼治疗已显示对经治的转移性乳腺癌（mBC）患者产生客观缓解。口服长春瑞滨也有望成为mBC患者的治疗选择。本研究旨在探讨口服长春瑞滨-阿帕替尼联合方案治疗经治mBC患者的疗效和安全性。此外，我们检测了循环肿瘤DNA（ctDNA）中的基因变异，以探索其治疗意义。
本研究纳入了接受过蒽环类/紫杉类药物治疗的人表皮生长因子受体2（HER2）阴性mBC患者。患者在每个周期（3周）的第1、8和15天接受阿帕替尼每日500 mg/425 mg加口服长春瑞滨60 mg/m²治疗。主要终点是无进展生存期（PFS）。次要终点是客观缓解率（ORR）、临床受益率（CBR）、总生存期（OS）和安全性。符合ctDNA检测条件的患者在治疗前和治疗期间进行评估。
共纳入40例患者。中位PFS为5.2个月（95%置信区间[CI]，3.4 - 7.0个月），中位OS为17.4个月（95% CI，8.0 - 27.0个月）。ORR为17.1%（6/35），CBR为45.7%（16/35）。最常见的不良反应包括胃肠道反应、骨髓抑制和高血压。20例患者在基线和治疗期间检测到ctDNA。未检测到基线ctDNA与检测到基线ctDNA的患者在PFS方面存在显著差异（13.9个月对3.6个月，P = 0.018）。
阿帕替尼联合长春瑞滨的全口服疗法在HER2阴性、经大量治疗的mBC患者中显示出客观疗效，且毒性特征可接受且易于管理。基线时未检测到基因变异且ctDNA中变异等位基因频率较低的患者PFS更长。
