Laboratory for Translational Breast Cancer Research, Department of Oncology, Leuven, Belgium.
Unit of Medical Statistics, Biometry and Bioinformatics Giulio A. Maccacaro Department of Clinical Sciences and Community Health & DSRC, University of Milan, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
J Clin Oncol. 2020 Sep 1;38(25):2883-2891. doi: 10.1200/JCO.19.01771. Epub 2020 Jul 2.
Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. Here, we reanalyzed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel-based chemotherapy in patients with breast cancer according to their baseline body mass index (BMI).
We retrospectively analyzed data from all of the patients in the adjuvant BIG 2-98 trial (ClinicalTrials.gov identifier: NCT00174655; N = 2,887) comparing non-docetaxel- to docetaxel-containing chemotherapy. BMI (kg/m) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status.
There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; = .21) and 1.27 (95% CI, 1.01 to 1.60; = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; = .007) and 1.63 (95% CI, 1.27 to 2.09; < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted = .06) and OS (adjusted = .04).
This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition-based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.
亲脂性药物，如紫杉烷类，对脂肪组织具有高亲和力，因此分布容积更高。在这里，我们重新分析了临床试验数据，以研究根据基线体重指数（BMI），接受基于多西紫杉醇与非多西紫杉醇化疗的乳腺癌患者的多西紫杉醇化疗的疗效是否存在差异。
我们回顾性分析了辅助 BIG 2-98 试验（ClinicalTrials.gov 标识符：NCT00174655；N=2887）中所有患者的数据，该试验比较了非多西紫杉醇与多西紫杉醇化疗。BMI（kg/m）分为以下几类：18.5 至 <25，瘦；25 至 <30，超重；≥30，肥胖。无病生存（DFS）是主要终点，总生存（OS）是次要终点。评估治疗、BMI 和雌激素受体（ER）状态之间的二级交互作用。
非多西紫杉醇组的 DFS 或 OS 与 BMI 无关，而多西紫杉醇组随着 BMI 类别的增加，DFS 和 OS 降低。DFS 和 OS 的调整后的风险比分别为超重与瘦体重组的 1.12（95%CI，0.98 至 1.50；=0.21）和 1.27（95%CI，1.01 至 1.60；=0.04），肥胖与瘦体重组分别为 1.32（95%CI，1.08 至 1.62；=0.007）和 1.63（95%CI，1.27 至 2.09；<0.001）。当分别考虑 ER 阴性和 ER 阳性肿瘤以及仅考虑接受多西紫杉醇相对剂量强度≥85%的患者时，得到了类似的结果。BMI 和 ER 状态对治疗效果的联合修饰作用在 DFS（调整后的=0.06）和 OS（调整后的=0.04）中都很明显。
这项对大型辅助试验的回顾性分析强调了根据 BMI 对多西紫杉醇的不同反应，这呼吁基于身体成分重新评估在乳腺癌中使用紫杉烷的风险-获益比。这些结果现在必须在其他系列中得到证实。
