晚期乳腺癌胸壁转移后阿帕替尼有效
由于乳腺癌胸壁转移灶的新生血管通常比较丰富，故可能对血管内皮生长因子受体VEGFR-2抑制剂阿帕替尼比较敏感。
2021年4月30日，中国抗癌协会旗下《中国癌症研究杂志》发表北京大学肿瘤医院李惠平、姜晗昉、宋国红、梁旭、河北医科大学第四医院耿翠芝、北京大学第三医院赵红梅、天津医科大学肿瘤医院佟仲生、解放军总医院杨俊兰等学者的CABC006研究报告，探讨了阿帕替尼单药或联合内分泌治疗对HER2阴性晚期乳腺癌胸壁转移的临床效果。
CABC006 (NCT02878057): Multicenter Phase II Study of Apatinib in Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis
该多中心单组非盲二期临床研究于2016年9月～2019年7月从中国4个中心入组HER2阴性晚期乳腺癌胸壁转移患者26例，每天口服阿帕替尼500毫克（单药，若激素受体阳性则联合内分泌治疗）直至疾病进展或毒性无法耐受。主要终点为无进展生存。
结果，截至2020年3月30日，随访3～55个月（中位18个月）
无进展生存：中位4.9个月（范围：2.0～28.5，95%置信区间：2.1～8.3）
总生存时间：中位18个月（范围：3～55，95%置信区间：12.9～23.1）
客观缓解率：42.3%（11例）
病变控制率：76.9%（20例）
根据亚组分析，激素受体阳性与阴性患者相比：
无进展生存：中位7.0个月比2.3个月（95%置信区间：2.2～11.8、1.2～3.4，P=0.001）
胸壁放疗与未放疗患者相比：
无进展生存：中位6.4个月比3.0个月（95%置信区间：1.6～19.5、1.3～4.6，P=0.041）
根据多因素分析，激素受体阳性是有利于无进展生存的唯一独立预测因素（P=0.014）。
发生率最高的不良事件包括：高血压50.0%、蛋白尿33.3%、恶心13.3%，其中3级不良事件发生率合计40%，未见4级不良事件。
因此，该小样本初步研究结果表明，阿帕替尼对乳腺癌胸壁转移患者疗效显著，尤其对于激素受体阳性患者联合内分泌治疗时。无论胸壁是否放疗，激素受体阳性患者的无进展生存显著较长。不过，3级不良事件发生率达40%，应从阿帕替尼治疗开始时就密切监测。
Multicenter phase II study of apatinib single or combination therapy in HER2-negative breast cancer involving chest wall metastasis.
Li H, Geng C, Zhao H, Jiang H, Song G, Zhang J, Liu Y, Gui X, Wang J, Li K, Tong Z, Zhao F, Yang J, Chen G, Liu Q, Liang X.
Peking University Cancer Hospital & Institute, Beijing, China; Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China; Peking University Third Hospital, Beijing, China; Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; University of Chicago, Chicago, USA; Chinese PLA General Hospital, Beijing, China; Jiangsu Hengrui Medicine Co. Ltd., Shanghai, China.
OBJECTIVE: Breast cancer (BC) with chest wall metastasis (CWM) usually shows rich neovascularization. This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2 (HER2)-negative advanced BC involving CWM.
METHODS: This trial involved four centers in China and was conducted from September 2016 to March 2020. Patients received apatinib 500 mg/d [either alone or with endocrine therapy if hormone receptor-positive (HR+)] until disease progression or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint.
RESULTS: We evaluated 26 patients for efficacy. The median PFS (mPFS) and median overall survival (mOS) were 4.9 [range: 2.0-28.5; 95% confidence interval (95% CI): 2.1-8.3] months and 18 (range: 3-55; 95% CI: 12.9-23.1) months, respectively. The objective response rate (ORR) was 42.3% (11/26), and the disease-control rate was 76.9% (20/26). In the subgroup analysis, HR+ patients compared with HR-negative patients had significantly improved mPFS of 7.0 (95% CI: 2.2-11.8) monthsvs. 2.3 (95% CI: 1.2-3.4) months, respectively (P=0.001); and mPFS in patients without or with chest wall radiotherapy was 6.4 (95% CI: 1.6-19.5) monthsvs. 3.0 (95% CI: 1.3-4.6) months, respectively (P=0.041). In the multivariate analysis, HR+ status was the only independent predictive factor for favorable PFS (P=0.014).
CONCLUSIONS: Apatinib was highly effective for BC patients with CWM, especially when combined with endocrine therapy. PFS improved significantly in patients with HR+ status who did not receive chest wall radiotherapy. However, adverse events were serious and should be carefully monitored from the beginning of apatinib treatment.
KEYWORDS: Apatinib; HER2-negative; advanced breast cancer; chest wall metastasis
PMID: 34158743
PMCID: PMC8181870
DOI: 10.21147/j.issn.1000-9604.2021.02.11