Frequent Pathologic Complete Responses in Aggressive Stages II to III Breast Cancers With Every-4-Week Carboplatin and Weekly Paclitaxel With or Without Trastuzumab: A Brown University Oncology Group Study
Frequent Pathologic Complete Responses in Aggressive Stages II to III Breast Cancers With Every-4-Week Carboplatin and Weekly Paclitaxel With or Without Trastuzumab: A Brown University Oncology Group Study
复制标题
DOI：
10.1200/jco.2008.21.4163
复制
发表时间：
2009-10-01
影响因子：
45.3
通讯作者：
Fenton, Mary Anne
中科院分区：
文献类型：
--
作者：
Sikov, William M.;Dizon, Don S.;Fenton, Mary Anne
目的评价新辅助卡铂和每周紫杉醇+/-每周曲妥珠单抗治疗可切除和局部晚期乳腺癌的疗效和安全性。患者与方法IIA~IIIB期乳腺癌患者接受卡铂每4周一次曲线下面积的6倍剂量，紫杉醇80 mg/m(2)每周一次，连续16周，每周加用曲妥珠单抗治疗人表皮生长因子受体2(HER2)阳性状态。主要终点是病理完全应答率，定义为乳房和腋窝结节无侵袭性疾病。术后的治疗由治疗医生决定。结果55名患者入选，其中43名患者有可切除的疾病。中位年龄54岁(31~74岁)。治疗耐受性良好；没有出现发热性中性粒细胞减少或4级血小板减少，只有2例3级周围神经病变。总体而言，PCR率为45%。在可切除疾病患者中，PCR率为43%(95%可信区间为28%~58%)。HER2阳性肿瘤(76%对HER2阴性肿瘤；P=.003)、雌激素受体(ER)阴性肿瘤(75%对ER阳性肿瘤；P=.001)或三阴性肿瘤(67%对12%ER阳性和HER2阴性肿瘤；P=.002)患者的PCR率较高。术后中位时间28个月，无复发生存率为88.7%。如果将ER阳性和HER2阴性的肿瘤患者排除在分析之外，获得PCR的患者发生疾病复发的可能性(RFS，86%)低于未获得PCR者(RFS，75%)。结论新辅助卡铂和每周一次的紫杉醇+/-曲妥珠单抗在HER2阳性和三阴性的疾病患者中获得高的PCR率，而不接触蒽环类药物。RFS的初步结果令人鼓舞，但可能受到所接受的辅助治疗的影响。在高危患者中对该方案进行额外的研究是必要的。
PurposeTo evaluate the efficacy and safety of neoadjuvant carboplatin and weekly paclitaxel +/- weekly trastuzumab in resectable and locally advanced breast cancer.Patients and MethodsWomen with stages IIA to IIIB disease received carboplatin dosed by six times the area under the curve every 4 weeks and paclitaxel 80 mg/m(2) weekly for 16 weeks, and weekly trastuzumab was added for human epidermal growth factor receptor 2 (HER2)-positive status. The primary end point was the pathologic complete response (pCR) rate, defined as the absence of invasive disease in the breast and axillary nodes. Postoperative therapies were at the discretion of the treating physicians.ResultsFifty-five patients were enrolled, and of these 43 had resectable disease. The median age was 54 years (range, 31 to 74 years). Treatment was well tolerated; there were no episodes of febrile neutropenia or grade 4 thrombocytopenia, and there were only two instances of grade 3 peripheral neuropathy. Overall, the pCR rate was 45%. The pCR rate was 43% (95% CI, 28% to 58%) in patients with resectable disease. Higher pCR rates occurred in patients with HER2-positive tumors (76% v 31% for HER2-negative tumors; P = .003), with estrogen receptor (ER)-negative tumors (75% v 27% for ER-positive tumors; P = .001), or with triple-negative tumors (67% v 12% ER-positive and HER2-negative tumors; P = .002). At a median of 28 months postoperation, recurrence-free survival (RFS) was 88.7%. If patients with ER-positive and HER2-negative tumors are excluded from analysis, patients who achieved a pCR were less likely to experience disease recurrence (RFS, 86%) than those who did not achieve a pCR (RFS, 75%).ConclusionNeoadjuvant carboplatin and weekly paclitaxel +/- trastuzumab achieve high pCR rates in patients with HER2-positive and triple-negative disease without exposure to an anthracycline. Preliminary RFS results are encouraging but are likely influenced by adjuvant therapy received. Additional study of this regimen in high-risk patients is warranted.