National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, P.R. China.
Ann Med. 2023 Dec;55(1):2218647. doi: 10.1080/07853890.2023.2218647.
More than half of the metastatic breast cancer patients with brain metastases (BCBM) are HER-2 negative, and the prognosis of HER2-negative BCBM is dismal. But few clinical trials have investigated systemic therapies for this subgroup of patients.
This real-world study included 58 HER2-negative BCBMs who received low-dose apatinib (250 mg daily) in combination with chemotherapy between 18 March 2017 and 31 December 2021. The objective response rate (ORR) of the central nervous system, clinical benefit rate (CBR), progression-free survival of central nervous system (CNS-PFS) and overall survival (OS) were analyzed. Univariate and multivariate Cox regression model was used to estimate the prognostic factors for CNS-PFS and OS.
At the cut-off date, the median follow-up time was 28.2 months. Of the 58 patients, 36 patients were HR+/HER2-, and 22 patients were TNBC. The CNS-ORR was 17.2% (95%CI 9.6% to 28.9%) and the CBR was 53.4% (95%CI 40.8% to 65.7%). The median duration of CNS-PFS for the entire cohort was 6.4 months, and the median OS was 10.7 months. The median CNS-PFS and OS were not affected by hormone receptor status, disease-free survival, the number of prior lines of therapy and local treatment. The most common grade 2-3 adverse events associated with low-dose apatinib were hypertension (20.6%), elevated bilirubin (10.4%), hypothyroidism (10.3%), and hand-foot skin reaction (10.3%).
Apatinib-based chemotherapy demonstrates potential feasibility with acceptable tolerance for HER2-negative BCBM. Its clinical application in BCBM still needs further verification.
超过一半的脑转移乳腺癌（BCBM）患者HER-2 阴性，HER-2 阴性 BCBM 的预后较差。但很少有临床试验研究过针对这一亚组患者的全身治疗方法。
本真实世界研究纳入了 2017 年 3 月 18 日至 2021 年 12 月 31 日期间接受低剂量阿帕替尼（250mg 每日）联合化疗的 58 例 HER-2 阴性 BCBM 患者。分析了中枢神经系统的客观缓解率（ORR）、临床获益率（CBR）、中枢神经系统无进展生存期（CNS-PFS）和总生存期（OS）。采用单因素和多因素 Cox 回归模型估计 CNS-PFS 和 OS 的预后因素。
在截止日期时，中位随访时间为 28.2 个月。58 例患者中，36 例为 HR+/HER-2-，22 例为三阴性乳腺癌。中枢神经系统 ORR 为 17.2%（95%CI 9.6%至 28.9%），CBR 为 53.4%（95%CI 40.8%至 65.7%）。全队列的中枢神经系统 PFS 中位持续时间为 6.4 个月，中位 OS 为 10.7 个月。中枢神经系统 PFS 和 OS 不受激素受体状态、无疾病生存期、治疗线数和局部治疗的影响。与低剂量阿帕替尼相关的最常见 2-3 级不良事件是高血压（20.6%）、胆红素升高（10.4%）、甲状腺功能减退（10.3%）和手足皮肤反应（10.3%）。
阿帕替尼为基础的化疗对 HER-2 阴性 BCBM 具有潜在的可行性，且耐受性可接受。其在 BCBM 中的临床应用仍需进一步验证。
