Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, Via del Pozzo 71 -, 41122, Modena, Italy.
Department of Bio-Statistics, RCCS Regina Elena National Cancer Institute, 00144, Rome, Italy.
BMC Cancer. 2020 May 13;20(1):418. doi: 10.1186/s12885-020-06933-y.
Elderly patients are underrepresented in clinical study where combined endocrine strategies were compared to endocrine therapy (ET) in hormone receptors positive, HER2 negative, metastatic breast cancer. The role of the new endocrine approaches in elderly women is still unclear.
We performed a meta-analysis of first line phase II/III randomized trials on ET versus combined strategies considering clinical benefit and safety profile. Trials with hazard ratio (HR) for PFS in elderly patients were included.
Overall, the meta-analysis showed a PFS advantage for the experimental arms [HR 0.77, p 0.016] with a significant high/moderate heterogeneity [I2 65.46%, p 0.005]. For patients on CDK 4/6 inhibitors and ET, HR was 0.57 (p < 0.0001), with low heterogeneity [I2 0.0001%, p 0.96]. Hematological adverse events, as well as diarrhea with Abemaciclib, were significantly higher in elderly population.
The magnitude of PFS benefit due to the combined strategies in elderly patients is similar to those reported in the overall clinical trial population. Adding CDK4/6 inhibitors to ET significantly prolongs PFS, even if toxicity profile have to be carefully considered. Future trials should be designed taking into account patients' age, geriatric assessment and comorbidity.
在激素受体阳性、HER2 阴性、转移性乳腺癌的临床研究中，老年患者代表性不足，这些研究比较了联合内分泌治疗策略与内分泌治疗（ET）。新的内分泌治疗方法在老年女性中的作用仍不清楚。
我们对一线 II/III 期随机试验进行了荟萃分析，比较了 ET 与联合治疗策略，考虑了临床获益和安全性特征。包括了在老年患者中具有无进展生存期（PFS）风险比（HR）的试验。
总体而言，荟萃分析显示实验臂具有 PFS 优势[HR 0.77，p 0.016]，且存在显著的高/中度异质性[I2 65.46%，p 0.005]。对于接受 CDK4/6 抑制剂和 ET 的患者，HR 为 0.57（p<0.0001），异质性较低[I2 0.0001%，p 0.96]。在老年人群中，血液学不良事件以及阿贝西利引起的腹泻发生率更高。
与总体临床试验人群相比，联合治疗策略在老年患者中带来的 PFS 获益幅度相似。即使需要仔细考虑毒性特征，将 CDK4/6 抑制剂加入 ET 也能显著延长 PFS。未来的试验应考虑患者年龄、老年评估和合并症等因素进行设计。
