Randomized phase II clinical trial and biomarker analysis of paclitaxel plus epirubicin versus vinorelbine plus epirubicin as neoadjuvant chemotherapy in locally advanced HER2-negative breast cancer withTEKT4variations
Randomized phase II clinical trial and biomarker analysis of paclitaxel plus epirubicin versus vinorelbine plus epirubicin as neoadjuvant chemotherapy in locally advanced HER2-negative breast cancer withTEKT4variations
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紫杉醇加表阿霉素与长春瑞滨加表阿霉素作为新辅助化疗治疗具有 TEKT4 变异的局部晚期 HER2 阴性乳腺癌的随机 II 期临床试验和生物标志物分析
DOI：
10.1007/s10549-020-05940-8
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发表时间：
2020-09-25
影响因子：
3.8
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Jiang, Yi-Zhou;Ge, Li-Ping;Shao, Zhi-Ming
目的紫杉醇耐药性仍然是治疗乳腺癌的主要挑战。我们的临床前研究表明乳腺癌中TEKT 4生殖细胞变异与紫杉醇耐药和增加长春瑞滨敏感性有关。本临床试验比较了紫杉醇和长春瑞滨在乳腺癌新辅助化疗中的疗效。MethodsIn this open-label，single center，phase II trial，女性患者人表皮生长因子受体2（HER 2）阴性，IIB-IIIC期乳腺癌harboringTEKT 4 germline variations被随机分配到紫杉醇加表阿霉素（PE）或长春瑞滨加表阿霉素（NE）。主要终点为病理学完全缓解（pCR）率，次要终点为客观缓解率（ORR）和安全性。对484个乳腺相关基因进行靶向测序，以确定各组中pCR相关的体细胞突变。结果91例患者被分为PE组（46例）或NE组（45例）。NE组pCR率为22.2%vs8.7%，P = 0.074。NE和PE的ORR分别为82.2%和76.1%。有趣的是，在激素受体（HR）阳性亚组中，NE（15.4%）的pCR率显著高于PE（0%）（P= 0.044）。两种方案均耐受良好，3级和4级毒性报告在预期水平。结论尽管未达到主要终点，但NE对HR阳性或同时携带UNC 13 D突变的患者可能带来临床获益。
PurposeResistance to paclitaxel remains a major challenge in treating breast cancer. Our preclinical study suggested thatTEKT4germline variations in breast cancer are associated with paclitaxel resistance and increase vinorelbine sensitivity. This clinical trial compared the efficacy of paclitaxel and vinorelbine in breast cancer neoadjuvant chemotherapy.MethodsIn this open-label, single-center, phase II trial, female patients with human epidermal growth factor receptor 2 (HER2)-negative, stage IIB–IIIC breast cancer harboringTEKT4germline variations were randomly assigned to the paclitaxel plus epirubicin (PE) or vinorelbine plus epirubicin (NE). The primary endpoint was the pathologic complete response (pCR) rate, and the secondary endpoints were the objective response rate (ORR) and safety. Targeted sequencing of a panel comprising 484 breast-related genes was performed to identify pCR-associated somatic mutations in each group.Results91 Patients were assigned to PE (46 patients) or NE (45 patients). NE numerically increased the pCR rate (22.2% versus 8.7%,P= 0.074). The ORRs for NE and PE were 82.2% and 76.1%, respectively. Interestingly, NE (15.4%) showed a significantly higher pCR rate than PE (0%) in the hormone receptor (HR)-positive subgroup (P= 0.044). Both regimens were well tolerated, with grade 3 and 4 toxicities reported at the expected levels. The biomarker analysis showed thatUNC13Dmutation predicted the pCR rate in NE (P= 0.011).ConclusionsAlthough the primary endpoint was not met, NE might bring clinical benefit to HR-positive patients or patients simultaneously carryingUNC13Dmutations.