在超重和肥胖的绝经后、激素受体阳性、HER2 阴性转移性乳腺癌患者中,二甲双胍、依维莫司和依西美坦联合治疗的疗效和安全性:一项 II 期研究。
Efficacy and safety of the combination of metformin, everolimus and exemestane in overweight and obese postmenopausal patients with metastatic, hormone receptor-positive, HER2-negative breast cancer: a phase II study.
机构信息
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1354, Houston, TX, 77030, USA.
Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
出版信息
Invest New Drugs. 2019 Apr;37(2):345-351. doi: 10.1007/s10637-018-0700-z. Epub 2019 Jan 5.
Background Increased adiposity is thought to result in worse clinical outcomes in patients with breast cancer through increased estrogen production, hyperinsulinemia, insulin resistance, and activation of the phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin (mTOR) pathway. Thus, we hypothesized that the addition of metformin to everolimus and exemestane, could lead to better outcomes in overweight and obese patients with metastatic, hormone receptor-positive, HER2-negative breast cancer. We conducted a phase II trial to evaluate the efficacy and safety of the combination of metformin, everolimus and exemestane in overweight and obese postmenopausal women with metastatic, hormone receptor-positive, HER2-negative breast cancer. Methods Twenty-two patients with a body mass index ≥25 kg/m were treated with metformin 1000 mg twice daily, everolimus 10 mg daily and exemestane 25 mg daily. Median progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results Median PFS and OS were 6.3 months (95% confidence interval [CI]: 3.8-11.3 months) and 28.8 months (95% CI: 17.5-59.7 months), respectively. Five patients had a partial response and 7 had stable disease for ≥24 weeks yielding a clinical benefit rate of 54.5%. Compared with overweight patients, obese patients had an improved PFS on univariable (p = 0.015) but not multivariable analysis (p = 0.215). Thirty-two percent of patients experienced a grade 3 treatment-related adverse event (TRAE). There were no grade 4 TRAEs and 7 patients experienced a grade 3 TRAE. Conclusion The combination of metformin, everolimus and exemestane was safe and had moderate clinical benefit in overweight and obese with patients metastatic, hormone receptor-positive, HER2-negative breast cancer.
背景
人们认为,脂肪组织增加会导致乳腺癌患者雌激素产生增加、高胰岛素血症、胰岛素抵抗和磷脂酰肌醇-3-激酶/AKT/雷帕霉素哺乳动物靶标(mTOR)通路激活,从而导致临床结局恶化。因此,我们假设在超重和肥胖的转移性、激素受体阳性、HER2 阴性乳腺癌患者中,将二甲双胍添加到依维莫司和依西美坦中,可以带来更好的结果。我们进行了一项 II 期试验,以评估二甲双胍、依维莫司和依西美坦联合治疗超重和肥胖绝经后妇女转移性、激素受体阳性、HER2 阴性乳腺癌的疗效和安全性。
方法
22 例 BMI≥25kg/m2的患者接受二甲双胍 1000mg 每日 2 次、依维莫司 10mg 每日 1 次和依西美坦 25mg 每日 1 次治疗。使用 Kaplan-Meier 法估计中位无进展生存期(PFS)和总生存期(OS)。
结果
中位 PFS 和 OS 分别为 6.3 个月(95%CI:3.8-11.3 个月)和 28.8 个月(95%CI:17.5-59.7 个月)。5 例患者部分缓解,7 例患者 24 周以上疾病稳定,临床获益率为 54.5%。与超重患者相比,肥胖患者的 PFS 在单变量分析(p=0.015)而非多变量分析(p=0.215)中得到改善。32%的患者发生 3 级治疗相关不良事件(TRAE)。无 4 级 TRAE,7 例患者发生 3 级 TRAE。
结论
二甲双胍、依维莫司和依西美坦联合治疗超重和肥胖的转移性、激素受体阳性、HER2 阴性乳腺癌患者安全且具有中等临床获益。