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【ASCO 中国之声】袁芃教授：三阴乳腺癌辅助化疗的可能替代方案

2016年05月26日

作者：袁芃教授

单位：中国医学科学院肿瘤医院内科

来源：肿瘤资讯

卡铂+紫杉类（TP）对比表阿霉素+环磷酰胺序贯紫杉类（EC-T）用于三阴性乳腺癌辅助治疗的随机对照临床研究

摘要编号: 1068

Citation：J Clin Oncol 34, 2016 (suppl; abstr1068)

背景：铂类是直接破坏肿瘤细胞DNA的一类化疗药物，而三阴性乳腺癌尤其是携带BRCA1/2突变的患者，由于DNA修复能力存在缺陷，因此更容易对铂类药物敏感。近年来多项临床研究表明，将铂类用于治疗三阴性乳腺癌可显著改善此类型患者预后。但既往研究都是局限于新辅助治疗和姑息治疗领域，而本研究是迄今首个评价铂类用于三阴性乳腺癌辅助治疗效果的临床研究

方法：本研究为随机对照非劣效研究，共入组318名病理证实的三阴性乳腺癌病例，所有患者均接受根治性手术。按1：1随机分为研究组（TP：多西他赛 75mg/m^2 或紫杉醇175mg/m^2，第1天；卡铂 AUC 5，第1天；三周重复，共6周期）或对照组（EC-T：4周期表阿霉素 90mg/m^2，环磷酰胺 600mg/m^2 第1天；序贯4周期多西他赛75mg/ m^2 或紫杉醇175mg/m^2；三周重复，共8周期）。主要研究终点是3年无复发生存率，次要研究终点包括安全性和3年总生存率。留取患者治疗前血标本用于后续生物标记物分析。

结果：截止至2015年6月，163名患者入组EC-T组，155名患者入组TP组。两组淋巴结阴性患者比例分别为60.1%和70.1%。中位随访时间为31个月，共发生复发事件34例。EC-T组和TP组3年无复发生存率分别为86.4%和88.2%（HR=1.11，95% CI：0.56-2.18，P= 0.764）；3年总生存率分别为97.2%和95.3%（HR=0.75; 95% CI：0.17 -3.36; P= 0.707）。相比之下，EC-T组患者不良反应发生率更高，3/4度中性粒细胞下降、3/4度白细胞下降、3/4度脱发、1-4度贫血、1-4度外周神经毒性以及1-4度肌肉疼痛发生率均显著高于TP组。而血小板下降则更多见于TP组。心脏相关不良事件两组无显著差异。无治疗相关死亡出现。

结论：卡铂联合紫杉类药物也是三阴性乳腺癌一种可选择的辅助治疗方案，不良反应发生率相对较低。后续的生物标记物分析将进一步提示我们哪类患者能够从含铂方案中得到最多的获益。

临床研究信息：ClinicalTrials.gov identiﬁer NCT01150513

壁报展出时间：2016.6.5 8:00-11:30 乳腺癌-三阴/细胞毒/局部治疗专场

Comparison of four cycles epirubicin andcyclophosphamide (EC) followed by four cycles docetaxel (T) versus six cyclesdocetaxel and carboplatin (TP) as adjuvant chemotherapy for women with operabletriple negative breast cancer.

Abstract:

Background: Todetermine optimal adjuvant chemotherapy for early triple negative breast cancerdepends on efficacy and toxicity. We sought to examine if six cycles TP isnon-inferior to standard four cylces EC followed by four cycles T but withshorter treatment duration and reduced toxicity. Methods: Ptswith operable triple negative breast cancer were enrolled and randomized (1:1)to receive either six cycles TP (docetaxel:75 mg/m2; carboplatin:AUC = 5, day 1) or four cycles EC(epirubicin: 90 mg/m2;cyclophosphamide :600mg/m2 , day 1) followed by four cycles T(docetaxel : 100mg/m2 , day 1). Both regimens were repeatedevery three weeks. Randomization was stratified by lymph node status. Theprimary end point was median DFS. A sample size of 500 patients were requiredto detect the difference (a = 0.05, β = 80%). Results: FromJune 2010 to Jan 2015, 298 pts were enrolled in the study including 152 pts inEC-T arm and 146 pts in ET arm. Patients’ characteristics were well balancedbetween two arms. In total, 60.5% and 69.9% of patients were node-negative inEC-T arm and TP arm, respectively. In addition, the proportion of patientsdiagnosed as TNM Stage I, II and III was 33.6%, 55.3% and 11.2% in EC-T arm,whereas it accounted for 39.0%, 54.1% and 6.2% in TP arm. After median 39.5months followed-up, 32 events were observed (16 in EC-T, 16 in TP). The 5y DFSwas 83.8% in EC-T arm and 80.0% in TP arm (log-rank p = 0.961, HR 0.983, 95%CI= 0.490—1.970). Both regimens were well tolerated. The most frequent hematologicaltoxicity was neutropenia (Grade 3/4: 67.8% in EC-T vs. 39.0% in EP). The mostfrequent non- hematological toxicity were anorexia (All Grades: 80.3% in EC-Tvs. 62.3% in EP), liver dysfunction (All Grades: 32.2% in EC-T vs. 24.0% inEP), and neurosensory difficulties (All Grades: 26.3% in EC-T vs. 15.8% inTP). Conclusions: Benefit from six cycles TPwas similar as from four cycles EC followed by four cycles T, with lowertoxicity observed in patients with operable triple negative breast cancer.Clinical trial information: NCT01150513