Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer-8-year results of the Breast International Group 02-98 phase III trial
Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer-8-year results of the Breast International Group 02-98 phase III trial
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DOI：
10.1093/annonc/mds627
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发表时间：
2013-05-01
影响因子：
50.5
通讯作者：
Di Leo, A.
中科院分区：
文献类型：
--
作者：
Oakman, C.;Francis, P. A.;Di Leo, A.
背景：在结节阳性乳腺癌患者中，乳腺国际组织(BIG)02-98测试了多西紫杉醇(Taxotere)与以阿霉素(ADR)为基础的化疗方案的结合情况，并比较了序贯和同步方案。5年后，使用多西他赛有改善无病生存率(DFS)的趋势。方法：患者被随机分配到四种治疗方法之一：(I)序贯对照：阿霉素(A)(75 mg/m(2))×4-GT；经典环磷酰胺、甲氨蝶呤、5-氟尿嘧啶(CMF)；(Ii)同时对照：阿霉素、环磷酰胺(AC)(60/600 mg/m(2))×4-GT；CMF；(Iii)序贯多西紫杉醇：A(75 mg/m(2))x3-GT；多西紫杉醇(T)(100 mg/m(2))x3。联合用药：(50/75 mg/m(2))×4-gt；cmf。初步比较评估了多西紫杉醇的疗效，而不考虑时间表。在生物学定义的亚型内进行探索性分析。结果：2,887名患者入选。经过93.4个月的中位随访期，共有916例DFS事件。在初步比较中，多西紫杉醇对DFS无显著改善[危险比(HR)=0.91，95%可信区间(CI)=0.80-1.05，P=0.187]。在二次比较中，序贯多西紫杉醇明显改善DFS(HR=0.81，95%CI=0.67~0.99，P=0.036)，显著改善DFS(HR=0.84，95%CI=0.72~0.99，P=0.035)和总生存期(OS)(HR=0.79，95%CI=0.65~0.98，P=0.028)。Lumina-A病预后最好。HRS支持在除鲁米诺-A外的所有亚型中加入序贯多西紫杉醇；但由于数量有限，这一观察结果没有得到统计学上的支持。结论：随着进一步的随访，序贯多西紫杉醇方案导致的OS显著好于同时进行的阿霉素-多西紫杉醇方案，并且继续显示出比以阿霉素为基础的序贯对照更好的DFS。
Background: In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes.Methods: Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m(2)) x 4 -> classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m(2)) x 4 -> CMF; (iii) sequential docetaxel: A (75 mg/m(2)) x3 -> docetaxel (T) (100 mg/m(2)) x3. CMF and (iv) concurrent docetaxel: AT(50/75 mg/m(2)) x 4 -> CMF. The primary comparison evaluated docetaxel efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes.Results: Two thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant improvement in DFS from docetaxel [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.80-1.05, P = 0.187]. In secondary comparisons, sequential docetaxel significantly improved DFS compared with sequential control (HR = 0.81, 95% CI = 0.67-0.99, P = 0.036), and significantly improved DFS (HR = 0.84, 95% CI = 0.72-0.99, P = 0.035) and overall survival (OS) (HR = 0.79, 95% CI = 0.65-0.98, P = 0.028) compared with concurrent doxorubicin-docetaxel. Luminal-A disease had the best prognosis. HRs favored addition of sequential docetaxel in all subtypes, except luminal-A; but this observation was not statistically supported because of limited numbers.Conclusion: With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control.