Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Department of Oncology, Oslo University Hospital, Oslo, Norway.
Int J Cancer. 2020 Nov 1;147(9):2515-2525. doi: 10.1002/ijc.33108. Epub 2020 Jun 18.
Antiangiogenic drugs are potentially a useful supplement to neoadjuvant chemotherapy for a subgroup of patients with human epidermal growth factor receptor 2 (HER2) negative breast cancer, but reliable biomarkers for improved response are lacking. Here, we report on a randomized phase II clinical trial to study the added effect of bevacizumab in neoadjuvant chemotherapy with FEC100 (5-fluorouracil, epirubicin and cyclophosphamide) and taxanes (n = 132 patients). Gene expression from the tumors was obtained before neoadjuvant treatment, and treatment response was evaluated by residual cancer burden (RCB) at time of surgery. Bevacizumab increased the proportion of complete responders (RCB class 0) from 5% to 20% among patients with estrogen receptor (ER) positive tumors (P = .02). Treatment with bevacizumab was associated with improved 8-year disease-free survival (P = .03) among the good responders (RCB class 0 or I). Patients treated with paclitaxel (n = 45) responded better than those treated with docetaxel (n = 21; P = .03). Improved treatment response was associated with higher proliferation rate and an immune phenotype characterized by high presence of classically activated M1 macrophages, activated NK cells and memory activated CD4 T cells. Treatment with bevacizumab increased the number of adverse events, including hemorrhage, hypertension, infection and febrile neutropenia, but despite this, the ECOG status was not affected.
抗血管生成药物可能对人表皮生长因子受体 2（HER2）阴性乳腺癌患者的亚组是一种有用的辅助新辅助化疗药物，但缺乏可靠的生物标志物来提高反应率。在这里，我们报告了一项随机 II 期临床试验，研究贝伐珠单抗在 FEC100（5-氟尿嘧啶、表柔比星和环磷酰胺）和紫杉烷类新辅助化疗中的附加作用（n = 132 例患者）。在新辅助治疗前获得肿瘤的基因表达，并通过手术时的残留肿瘤负担（RCB）评估治疗反应。贝伐珠单抗使雌激素受体（ER）阳性肿瘤患者的完全缓解者（RCB 分级 0）比例从 5%增加到 20%（P =.02）。贝伐珠单抗治疗与良好反应者（RCB 分级 0 或 I）的 8 年无病生存率提高相关（P =.03）。接受紫杉醇治疗的患者（n = 45）比接受多西他赛治疗的患者（n = 21）反应更好（P =.03）。治疗反应的改善与更高的增殖率和免疫表型相关，其特征为经典激活的 M1 巨噬细胞、活化的 NK 细胞和记忆激活的 CD4 T 细胞的高存在。贝伐珠单抗治疗增加了不良事件的数量，包括出血、高血压、感染和发热性中性粒细胞减少症，但尽管如此，ECOG 状态并未受到影响。
