表柔比星等蒽环类药物是乳腺癌化疗方案的常用有效配方之一，但是具有心脏毒性，对于早期乳腺癌术后辅助化疗的作用仍有争论，尤其对于高风险早期乳腺癌患者，无蒽环辅助化疗方案的有效性和安全性尚不明确。
2019年2月20日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表德国西部研究协作组、贝塞斯达福音医院、科隆大学、特里尔圣母医院、罗斯托克城南医院、贝尔吉施格拉德巴赫福音医院、埃森大学医院、莱比锡大学、根廷施滕达尔约翰尼特医院、奥伯豪森新教医院、霍斯特施密特医院、希尔德斯海姆妇科肿瘤科医院的早期乳腺癌无蒽环辅助化疗B计划研究报告，比较了无蒽环辅助化疗方案（六个周期多西他赛75毫克＋环磷酰胺600毫克）、有蒽环辅助化疗方案（四个周期表柔比星90毫克＋环磷酰胺600毫克→四个周期多西他赛100毫克）对于HER2阴性早期乳腺癌的有效性和安全性（NCT01049425）。
该多中心随机对照研究于2009年2月～2011年12月入组病理T分期1～4c、淋巴结阳性、淋巴结阴性高风险（定义：病理T分期>2、分级2～3、uPA/PAI-1比值高、激素受体阴性、年龄<35岁）早期乳腺癌女性患者（研究方案早期调整后，所有激素受体阳性患者进行21基因复发评分检测，剔除了复发评分≤11、病理N分期0～1的低风险患者）共计2449例，按1∶1随机分为两组：
有蒽环组1227例（表柔比星90毫克＋环磷酰胺600毫克四个周期→多西他赛100毫克四个周期，每个周期21天）
无蒽环组1222例（多西他赛75毫克＋环磷酰胺600毫克六个周期，每个周期21天）
主要研究终点为5年无病生存；次要研究终点为5年总体生存和安全性。研究方案预设5年无病生存率相差4.4%为所有患者合并非劣效临界值（P=0.05）。
结果，中位随访60个月，有蒽环组与无蒽环组相比：
绝经后患者：62.2%比60.8%
淋巴结阴性：58.2%比59.5%
病理分期T1：57.6%比52.3%
激素受体阳性：81.4%比82.2%
激素受体阳性复发评分>25：26.2%比27.5%
实际治疗例数：1167比1178
完成治疗比例：87.5%比93.0%
无病生存率：89.6%比89.9%（95%置信区间：87.9%～91.5%、88.1%～91.8%）
总体生存率：94.5%比94.7%（95%置信区间：93.1%～95.9%、93.3%～96.1%）
治疗相关死亡例数：1比5
无病生存率差值符合原始研究设计非劣效范围。虽然无蒽环组治疗相关死亡例数较多，但是有蒽环组严重不良事件较多。交互作用分析表明，关键因素（三阴性、激素受体阳性、病理N分期、年龄、复发评分）无预测作用。
因此，根据德国西部研究协作组B计划研究结果，有、无蒽环辅助化疗方案的5年结局相似。六个周期多西他赛＋环磷酰胺可以作为HER2阴性早期乳腺癌（病理分期为N0的21基因高风险，或者病理分期为N1的21基因中到高风险）患者安全有效的辅助化疗方案选择之一。
J Clin Oncol. 2019 Feb 20. [Epub ahead of print]
West German Study PlanB Trial: Adjuvant Four Cycles of Epirubicin and Cyclophosphamide Plus Docetaxel Versus Six Cycles of Docetaxel and Cyclophosphamide in HER2-Negative Early Breast Cancer.
Ulrike Nitz, Oleg Gluz, Michael Clemens, Wolfram Malter, Toralf Reimer, Benno Nuding, Bahriye Aktas, Andrea Stefek, Anke Pollmanns, Fatemeh Lorenz-Salehi, Christoph Uleer, Petra Krabisch, Sherko Kuemmel, Cornelia Liedtke, Steven Shak, Rachel Wuerstlein, Matthias Christgen, Ronald E. Kates, Hans H. Kreipe, Nadia Harbeck; West German Study Group PlanB Investigators.
West German Study Group, Monchengladbach, Germany; Evangelical Hospital Bethesda, Monchengladbach, Germany; University of Cologne, Cologne, Germany; Mutterhaus der Borromaerinnen, Trier, Germany; Clinics Suedstadt, Rostock, Germany; Evangelical Hospital Bergisch Gladbach, Bergisch Gladbach, Germany; University Clinics Essen, Essen, Germany; University of Leipzig, Leipzig, Germany; Johanniter-Krankenhaus Genthin-Stendal Hospitals, Stendal, Germany; Protestant Hospital Oberhausen, Oberhausen, Germany; Horst-Schmidt-Kliniken, Wiesbaden, Germany; Gynecological-Oncological Practice, Hildesheim, Germany.
PURPOSE: The West German Study Group PlanB trial evaluated an anthracycline-free chemotherapy standard (six cycles of docetaxel and cyclophosphamide [TC]) in the routine treatment of human epidermal growth factor receptor 2-negative early breast cancer (EBC).
PATIENTS AND METHODS: Patients with pT1 to pT4c, all pN+, and pN0/high-risk EBC were eligible. High-risk pN0 was defined by one or more of the following: pT greater than 2, grade 2 to 3, high urokinase-type plasminogen activator/plasminogen activator inhibitor-1, hormone receptor (HR) negativity, and less than 35 years of age. After an early amendment, all HR-positive tumors underwent recurrence score (RS) testing, with chemotherapy omission recommended in RS less than or equal to 11 pN0 to pN1 disease. Patients were randomly assigned to four cycles of epirubicin (E)90/cyclophoshamide (C)600 followed by four cycles of docetaxel (T)100 or six cycles of T75C600 (administered once every 3 weeks). The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The protocol specified P = .05 for a noninferiority margin of 4.4% for all patients combined.
RESULTS: Of the 3,198 registered patients, 348 (RS ≤ 11) omitted chemotherapy, and 401 were not randomly assigned. The intention-to-treat population included 2,449 patients (1,227 EC-T v 1,222 TC: postmenopausal, 62.2% v 60.8%; pN0, 58.2% v 59.5%; pT1, 57.6% v 52.3%; HR positive, 81.4% v 82.2%; RS greater than 25 [in HR-positive patients], 26.2% v 27.5%). Within the safety population (1,167 v 1,178 patients), 87.5% v 93.0% completed therapy. After a 60-month median follow-up, 5-year outcomes were similar in the EC-T and TC arms (DFS, 89.6% [95% CI, 87.9% to 91.5%] v 89.9% [95% CI, 88.1% to 91.8%]; OS, 94.5% [95% CI, 93.1% to 95.9%] v 94.7% [95% CI, 93.3% to 96.1%]). The DFS difference was within the noninferiority margin of the original trial design. Five treatment-related deaths were reported for TC (one for EC-T), despite a trend toward more-severe adverse events in the latter. Interaction analysis revealed no predictive trends with respect to key factors, including triple-negative, luminal A/B-like, pN, age, and RS status.
CONCLUSION: In the West German Study Group PlanB trial, 5-year outcomes for TC and EC-T were equally excellent. Six cycles of TC is an effective/safe option in human epidermal growth factor receptor 2-negative EBC with pN0 high genomic risk or pN1 EBC with genomically intermediate- to high-risk disease.
PMID: 30785826
DOI: 10.1200/JCO.18.00028
联系客服
