Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G 2M9, Canada; Sackler Faculty of Medicine, Tel Aviv University, POB 39040, Tel Aviv 6997801, Israel.
Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G 2M9, Canada.
Cancer Treat Rev. 2018 Dec;71:68-75. doi: 10.1016/j.ctrv.2018.10.010. Epub 2018 Oct 17.
Many adjuvant breast cancer trials have observed smaller than anticipated differences between experimental and control groups. Accurate estimation of the absolute benefits of treatment is essential for the planning of clinical trials.
We searched PubMed to identify contemporary randomized trials comparing different adjuvant chemotherapy regimens in breast cancer. The absolute difference in 5-year disease-free survival (DFS) and overall-survival between experimental and control groups were extracted, weighted by individual study sample size and pooled. Analyses were performed for estrogen receptor (ER) negative and ER-positive disease. Meta-regression explored the influence of patients and tumor characteristics and median follow-up on the benefit from treatment.
Analysis included 19 studies comprising 41,564 patients. Studies comparing chemotherapy regimens of different generations showed the largest difference in 5-year DFS (+7.4% for 3rd vs. 2nd generation and +5.9% for 2nd vs. 1st generation for ER-negative disease, and +2.3% for 3rd vs. 2nd generation and +1.8% for 2nd vs. 1st generation for ER-positive disease). Studies comparing chemotherapy regimens from the same generation showed smaller differences in DFS in both subgroups. Meta-regression showed that larger tumors and nodal involvement had significant greater magnitude of effect on 5-year DFS for ER-negative, but not ER-positive disease. Age and menopausal status had no effect in either subgroup.
Absolute differences between adjuvant chemotherapy regimens of the same generation are small even in ER-negative disease. Enrichment of trials for patients with poor clinical features results in larger magnitudes of benefit from treatment at 5 years in ER-negative, but not ER-positive disease.
许多辅助乳腺癌试验观察到实验组和对照组之间的差异小于预期。准确估计治疗的绝对获益对于临床试验的规划至关重要。
我们在 PubMed 中搜索了比较乳腺癌不同辅助化疗方案的当代随机试验。从每个研究的样本量中提取实验组和对照组 5 年无病生存（DFS）和总生存的绝对差异，并进行加权汇总。对雌激素受体（ER）阴性和 ER 阳性疾病进行分析。Meta 回归分析探讨了患者和肿瘤特征以及中位随访时间对治疗获益的影响。
分析包括 19 项研究，共纳入 41564 例患者。比较不同代化疗方案的研究显示 5 年 DFS 的差异最大（ER 阴性疾病中第三代与第二代相比为+7.4%，第二代与第一代相比为+5.9%；ER 阳性疾病中第三代与第二代相比为+2.3%，第二代与第一代相比为+1.8%）。比较同一代化疗方案的研究在两个亚组中 DFS 的差异较小。Meta 回归显示，肿瘤较大和淋巴结受累对 ER 阴性疾病 5 年 DFS 的影响更大，但对 ER 阳性疾病无影响。年龄和绝经状态在两个亚组中均无影响。
即使在 ER 阴性疾病中，同一代辅助化疗方案之间的绝对差异也很小。在临床试验中富集具有较差临床特征的患者，可使 ER 阴性疾病的治疗获益在 5 年时显著增加，但对 ER 阳性疾病无影响。
