NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+or 2+
NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+or 2+
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DOI：
10.1200/jco.19.01455
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发表时间：
2020-02-10
影响因子：
45.3
通讯作者：
Wolmark, Norman
中科院分区：
文献类型：
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作者：
Fehrenbacher, Louis;Cecchini, Reena S.;Wolmark, Norman
目的
辅助性曲妥珠单抗可降低人表皮生长因子受体2（HER2）扩增或过表达的浸润性乳腺癌（IBC）患者的浸润性乳腺癌复发率和死亡风险。在具有里程碑意义的曲妥珠单抗辅助治疗试验中，有一部分患者最初检测为HER2阳性，但经中心HER2检测为HER2阴性，这些患者似乎可能从曲妥珠单抗治疗中获益。美国国家外科辅助乳腺和肠道项目（NSABP）B - 47试验的目的是确定在辅助化疗（CRx）中添加曲妥珠单抗是否会提高HER2阴性乳腺癌患者的浸润性无病生存期（IDFS）。
患者与方法
共有3270名高危原发性IBC女性被随机分配接受含或不含1年曲妥珠单抗的CRx治疗。入选标准包括免疫组化（IHC）评分1 +或2 +且荧光原位杂交比率（FISH）<2.0，或者如果未进行比率检测，则HER2基因拷贝数<4.0。CRx方案为多西他赛加环磷酰胺，或阿霉素和环磷酰胺后接着每周使用紫杉醇治疗12周。
结果
中位随访46个月时，在CRx中添加曲妥珠单抗并未改善IDFS（5年IDFS：CRx加曲妥珠单抗[CRxT]组为89.8%，单独CRx组为89.2%；风险比[HR]，0.98；95%置信区间，0.76 - 1.25；P = 0.85）。这些结果在HER2 IHC表达水平、淋巴结受累情况或激素受体状态方面无差异。对于无远处复发生存期，CRxT组5年估计值为92.7%，而单独CRx组为93.6%（HR，1.10；95%置信区间，0.81 - 1.50；P = 0.55）；对于总生存期（OS），CRxT组为94.8%，单独CRx组为96.3%（HR，1.33；95%置信区间，0.90 - 1.95；P = 0.15）。在CRx中添加曲妥珠单抗未出现意外毒性。
结论
在CRx中添加曲妥珠单抗并未改善非HER2过表达的IBC女性的IDFS、无远处复发生存期或总生存期。曲妥珠单抗对无IHC 3 +或FISH比率扩增的乳腺癌女性无益。（C）2019年美国临床肿瘤学会
PURPOSE Adjuvant trastuzumab reduces invasive breast cancer (IBC) recurrence and risk for death in patients with HER2-amplified or overexpressing IBC. A subset of patients in the landmark trastuzumab adjuvant trials who originally tested HER2-positive but were HER2-negative by central HER2 testing appeared to possibly benefit from trastuzumab. The objective for the NSABP B-47 trial was to determine whether the addition of trastuzumab to adjuvant chemotherapy (CRx) would improve invasive disease-free survival (IDFS) in patients with HER2-negative breast cancer.PATIENTS AND METHODS A total of 3,270 women with high-risk primary IBC were randomly assigned to CRx with or without 1 year of trastuzumab. Eligibility criteria included immunohistochemistry (IHC) score 1+ or 2+ with fluorescence in situ hybridization ratio (FISH) < 2.0 or, if ratio was not performed, HER2 gene copy number < 4.0. CRx was either docetaxel plus cyclophosphamide or doxorubicin and cyclophosphamide followed by weekly paclitaxel for 12 weeks.RESULTS At a median follow-up of 46 months, the addition of trastuzumab to CRx did not improve IDFS (5-year IDFS: 89.8% with CRx plus trastuzumab [CRxT] v 89.2% with CRx alone; hazard ratio [HR], 0.98; 95% CI, 0.76 to 1.25; P = .85). These findings did not differ by level of HER2 IHC expression, lymph node involvement, or hormone-receptor status. For distant recurrence-free interval, 5-year estimates were 92.7% with CRxT compared with 93.6% for CRx alone (HR, 1.10; 95% CI, 0.81 to 1.50; P = .55) and for overall survival (OS) were 94.8% with CRxT and 96.3% in CRx alone (HR, 1.33; 95% CI, 0.90 to 1.95; P = .15). There were no unexpected toxicities from the addition of trastuzumab to CRx.CONCLUSION The addition of trastuzumab to CRx did not improve IDFS, distant recurrence-free interval, or OS in women with non-HER2-overexpressing IBC. Trastuzumab does not benefit women without IHC 3+ or FISH ratio-amplified breast cancer. (C) 2019 by American Society of Clinical Oncology