Sonnenblick Amir, Francis Prudence A, Azim Hatem A, de Azambuja Evandro, Nordenskjöld Bo, Gutiérez Jorge, Quinaux Emmanuel, Mastropasqua Mauro G, Ameye Lieveke, Anderson Michael, Lluch Ana, Gnant Michael, Goldhirsch Aron, Di Leo Angelo, Barnadas Agusti, Cortes-Funes Hernan, Piccart Martine, Crown John
Department of Medicine, BrEAST Data Centre, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Peter MacCallum Cancer Centre, Melbourne, Australia; Australia and New Zealand Breast Cancer Trials Group Newcastle, Australia; International Breast Cancer Study Group, Bern, Switzerland.
Eur J Cancer. 2015 Aug;51(12):1481-9. doi: 10.1016/j.ejca.2015.03.018. Epub 2015 Jun 11.
Breast International Group (BIG) 2-98 is a randomised phase III trial that tested the effect of adding docetaxel, either in sequence to or in combination with anthracycline-based adjuvant chemotherapy, in women with node-positive breast cancer (BC). Here, we present the 10-year final trial safety and efficacy analyses. We also report an exploratory analysis on the predictive value of Ki67 for docetaxel efficacy, in the BIG 2-98 and using a pooled analysis of three other randomised trials.
2887 patients were randomly assigned in a 2×2 trial design to one of four treatments. The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival (DFS). Secondary objectives included comparisons of sequential docetaxel versus sequential control arm, safety and overall survival (OS). Ki67 expression was centrally evaluated by immunohistochemistry.
After a median follow-up of 10.1years, the addition of docetaxel did not significantly improve DFS or OS (hazard ratio (HR)=0.91, 95% confidence interval (CI)=0.81-1.04; P=0.16 and HR=0.88, 95% CI=0.76-1.03; P=0.11, respectively). Sequential docetaxel did not improve DFS compared to the sequential control arm (HR=0.86, 95% CI=0.72-1.03; P=0.10). In oestrogen receptor (ER)-positive tumours with Ki67⩾14%, the addition of docetaxel resulted in 5.4% improvement in 10-year OS (P=0.03, test for interaction=0.1). In a multivariate model, there was a trend for improved DFS and OS in ER-positive patients with high Ki67 and treated with docetaxel (HR=0.79, 95% CI=0.63-1.01; P=0.05 and HR=0.76, 95% CI=0.57-1.01; P=0.06, respectively). A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours (interaction test P=0.01).
The DFS benefit previously demonstrated with sequential docetaxel is no longer observed at 10years. However, an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC.
国际乳腺癌研究组（BIG）2-98是一项III期随机试验，旨在测试在淋巴结阳性乳腺癌（BC）女性患者中，将多西他赛序贯或联合蒽环类辅助化疗的效果。在此，我们展示了10年的最终试验安全性和疗效分析。我们还报告了一项关于Ki67对多西他赛疗效预测价值的探索性分析，该分析基于BIG 2-98试验以及对其他三项随机试验的汇总分析。
2887例患者按2×2试验设计随机分配至四种治疗方案之一。主要目的是评估多西他赛对无病生存期（DFS）的总体疗效。次要目的包括序贯多西他赛组与序贯对照组的比较、安全性和总生存期（OS）。Ki67表达通过免疫组织化学进行集中评估。
中位随访10.1年后，添加多西他赛并未显著改善DFS或OS（风险比（HR）=0.91，95%置信区间（CI）=0.81-1.04；P=0.16；HR=0.88，95%CI=0.76-1.03；P=0.11）。与序贯对照组相比，序贯多西他赛并未改善DFS（HR=0.86，95%CI=0.72-1.03；P=0.10）。在Ki67⩾14%的雌激素受体（ER）阳性肿瘤中，添加多西他赛使10年OS提高了5.4%（P=0.03，交互作用检验=0.1）。在多变量模型中，ER阳性且Ki67高并接受多西他赛治疗的患者有DFS和OS改善的趋势（HR=0.79，95%CI=0.63-1.01；P=0.05；HR=0.76，95%CI=0.57-1.01；P=0.06）。四项随机试验的汇总分析显示，紫杉烷类药物在高增殖性ER阳性疾病中有获益，但在低增殖性肿瘤中无获益（交互作用检验P=0.01）。
序贯多西他赛先前显示的DFS获益在10年后未再观察到。然而，一项探索性分析表明多西他赛对高增殖性ER阳性BC患者有益。
