Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Breast. 2019 Dec;48:17-23. doi: 10.1016/j.breast.2019.08.003. Epub 2019 Aug 22.
Pre-clinical data suggest metformin might enhance the effect of chemotherapy in breast cancer (BC). We conducted a Phase II randomized trial of chemotherapy plus metformin versus placebo in metastatic breast cancer (MBC).
In this double blind phase II trial we randomly assigned non-diabetic MBC patients on 1st to 4th line chemotherapy to receive metformin 850 mg po bid or placebo bid. Primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), response rate (RR), toxicity and quality of life (QOL). With 40 subjects and a type-one error of 0.2 (one-sided), a PFS hazard ratio (HR) of 0.58 could be detected with 80% power.
40 patients were randomized (22 metformin, 18 placebo) with a mean age of 55 vs 57 years and ER/PR positive BC in 86.4% vs 83.3% off metformin vs placebo, respectively. Mean BMI was 27kg/m2 in both arms. The majority of patients were on 1st line chemotherapy. Grade 3-4 toxicity occurred in 31.8% (metformin) vs 58.8% (placebo). Best response: Partial response 18.2% metformin vs 25% placebo, stable disease 36.4% metformin vs 18.8% placebo, progressive disease 45.4% metformin vs 56.2% placebo. Mean PFS was 5.4 vs 6.3 months (metformin vs placebo), HR 1.2 (95% CI 0.63-2.31). Mean OS was 20.2 (metformin) vs 24.2 months (placebo), HR 1.68 (95% CI 0.79-3.55).
In this population metformin showed no significant effect on RR, PFS or OS. These results do not support the use of metformin with chemotherapy in non-diabetic MBC patients.
临床前数据表明二甲双胍可能增强乳腺癌（BC）化疗的疗效。我们进行了一项转移性乳腺癌（MBC）中化疗加二甲双胍与安慰剂对照的 II 期随机试验。
在这项双盲 II 期试验中，我们将第 1 至 4 线化疗的非糖尿病性 MBC 患者随机分配接受二甲双胍 850mg 口服 bid 或安慰剂 bid。主要结局是无进展生存期（PFS）；次要结局包括总生存期（OS）、反应率（RR）、毒性和生活质量（QOL）。在 40 名受试者和 0.2 的一类错误（单侧）的情况下，可检测到 PFS 风险比（HR）为 0.58，具有 80%的功效。
40 名患者被随机分配（22 名二甲双胍，18 名安慰剂），平均年龄分别为 55 岁和 57 岁，ER/PR 阳性 BC 分别为 86.4%和 83.3%。二甲双胍组和安慰剂组的平均 BMI 分别为 27kg/m2。大多数患者处于一线化疗。3-4 级毒性分别发生在 31.8%（二甲双胍）和 58.8%（安慰剂）的患者中。最佳反应：部分缓解 18.2%二甲双胍 vs 25%安慰剂，稳定疾病 36.4%二甲双胍 vs 18.8%安慰剂，进展性疾病 45.4%二甲双胍 vs 56.2%安慰剂。平均 PFS 分别为 5.4 个月和 6.3 个月（二甲双胍 vs 安慰剂），HR 1.2（95%CI 0.63-2.31）。平均 OS 分别为 20.2 个月和 24.2 个月（二甲双胍 vs 安慰剂），HR 1.68（95%CI 0.79-3.55）。
在该人群中，二甲双胍对 RR、PFS 或 OS 无显著影响。这些结果不支持在非糖尿病性 MBC 患者中使用二甲双胍联合化疗。
