Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain.
Breast Cancer Res Treat. 2024 Aug;206(3):551-559. doi: 10.1007/s10549-024-07324-8. Epub 2024 May 4.
Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce.
A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates.
One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1-56 months). The median age at diagnosis was 49 years (range: 35-90 years). The estimated mPFS was 6.0 months (95%CI 5.3-7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6-11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8-10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9-8.4 months).
This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.
依维莫司联合内分泌治疗（ET）先前被批准用于 HR（+）/HER2（-）晚期乳腺癌（aBC）患者，这些患者在非甾体芳香酶抑制剂（NSAI）治疗期间或之后疾病进展。自该批准以来，aBC 的治疗格局发生了巨大变化，尤其是 CDK4-6 抑制剂的出现。CDK4/6 抑制剂进展后内分泌单药治疗的无进展生存期（PFS）有限，低于 3 个月。CDK4/6 抑制剂后依维莫司联合 ET 的疗效证据很少。
对 2015 年 2 月至 2022 年 12 月期间在西班牙 4 家医院接受 CDK4/6-i 进展后依维莫司联合 ET 治疗的 aBC 患者进行了回顾性观察性研究。从病历中收集临床和人口统计学数据。主要目的是估计中位无进展生存期（mPFS）。记录依维莫司的不良反应（AE）。定量变量用中位数表示；定性变量用比例表示，生存估计用 Kaplan-Meier 法。
161 例患者在 CDK4/6 抑制剂进展后接受了依维莫司联合 ET（依西美坦：96 例，氟维司群：54 例，他莫昔芬：10 例，未知：1 例）治疗。中位随访时间为 15 个月（四分位距：1-56 个月）。诊断时的中位年龄为 49 岁（范围：35-90 岁）。估计 mPFS 为 6.0 个月（95%CI 5.3-7.8 个月）。先前 CDK4/6 抑制剂治疗持续时间>18 个月的患者（8.7 个月，95%CI 6.6-11.3 个月）、无内脏转移的患者（8.0 个月，95%CI 5.8-10.5 个月）和转移性疾病时未经化疗的患者（7.2 个月，95%CI 5.9-8.4 个月）的 PFS 较长。
这项对先前接受 CDK4/6 抑制剂治疗的 mBC 患者依维莫司联合 ET 的回顾性分析队列表明，与当前随机临床数据中 ET 单药治疗的 mPFS 相比，估计 mPFS 更长。依维莫司联合 ET 可能被视为新型临床试验设计中有效的对照臂。
