Division of Medical Oncology, Department of Oncology, Western University, London Regional Cancer Program, 800 Commissioners road east, London, ON, N6A 5W9, Canada.
Department of Anatomy and Cell Biology, Western University, London, ON, Canada.
Target Oncol. 2020 Dec;15(6):723-732. doi: 10.1007/s11523-020-00770-6.
Everolimus plus exemestane is approved for the treatment of hormone receptor-positive metastatic breast cancer (MBC) after progression on nonsteroidal aromatase inhibitors. The role of everolimus is less well defined in other breast cancer phenotypes and in combination with other drugs.
We conducted a systematic review and meta-analysis to assess the efficacy and safety of adding everolimus to standard of care (SoC) in MBC regardless of tumor phenotype and treatment type.
The electronic databases PubMed and EMBASE were searched for eligible randomized trials. Pooled hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) and pooled risk ratios (RR) and odds ratios for objective response rates, disease control rate (DCR), and grade 3 or higher toxicity were meta-analyzed. Subgroup analyses compared survival outcomes by tumor phenotype.
Data from 2826 patients from eight trials were analyzed. The addition of everolimus to SoC reduced the risk of disease progression by 29% (HR 0.71; 95% confidence interval [CI] 0.56-0.90). This did not translate into an OS benefit (HR 0.95; 95% CI 0.80-1.13). In addition, everolimus improved the DCR (RR 0.82; 95% CI 0.68-0.98), whereas it increased the risk of developing grade 3 or higher toxicity. The PFS benefit was more prominent for patients with hormone receptor-positive (+)/human epidermal growth factor receptor 2 (HER2)-negative (-) disease. For the HER2 (+) subgroup, the PFS benefit was restricted to patients with hormone receptor (-) disease.
Everolimus reduces the risk of disease progression in hormone receptor (+) MBC. In patients with HER2 (+) disease, the benefit is limited for those with hormone receptor (-) disease. Given the approval and use of newer drugs in MBC, clinical trials and real-world data are needed to confirm the benefit of everolimus and define the best treatment sequence strategy to adopt in that setting.
依维莫司联合依西美坦获批用于非甾体芳香化酶抑制剂治疗进展后的激素受体阳性转移性乳腺癌（MBC）。依维莫司在其他乳腺癌表型和与其他药物联合治疗中的作用尚未明确。
我们进行了一项系统评价和荟萃分析，评估了依维莫司联合标准治疗（SoC）在 MBC 中的疗效和安全性，无论肿瘤表型和治疗类型如何。
检索电子数据库 PubMed 和 EMBASE，寻找合格的随机试验。对无进展生存期（PFS）和总生存期（OS）的合并风险比（HR）、客观缓解率（ORR）、疾病控制率（DCR）和 3 级或更高毒性的合并风险比（RR）和比值比（OR）进行荟萃分析。亚组分析比较了不同肿瘤表型的生存结局。
来自八项试验的 2826 名患者的数据进行了分析。与 SoC 相比，依维莫司联合治疗可降低 29%的疾病进展风险（HR 0.71；95%置信区间 [CI] 0.56-0.90）。但这并未转化为 OS 获益（HR 0.95；95% CI 0.80-1.13）。此外，依维莫司改善了 DCR（RR 0.82；95% CI 0.68-0.98），但增加了发生 3 级或更高毒性的风险。PFS 获益在激素受体阳性（+）/人表皮生长因子受体 2（HER2）阴性（-）疾病患者中更为显著。对于 HER2（+）亚组，PFS 获益仅限于激素受体（-）疾病患者。
依维莫司可降低激素受体阳性（+）MBC 患者的疾病进展风险。对于 HER2（+）疾病患者，该获益仅限于激素受体（-）疾病患者。鉴于在 MBC 中批准和使用了新型药物，需要临床试验和真实世界数据来证实依维莫司的获益，并确定在该治疗环境下采用的最佳治疗顺序策略。
