CDK4/6 抑制剂联合内分泌治疗与单独内分泌治疗用于高危浸润性 HR+/HER2-早期乳腺癌辅助治疗的疗效和安全性：随机临床试验的综合更新荟萃分析。

The efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in the adjuvant treatment of patients with high-risk invasive HR+/HER2-early breast cancer: A comprehensive updated meta-analysis of randomized clinical trials.

机构信息

Department of Medical Oncology, Faculty of Medicine, Dokuz Eylul University, İzmir, Turkiye.

Department of Biostatistics and Medical Informatics, Faculty of Medicine, Dokuz Eylul University, İzmir, Turkiye.

出版信息

Breast. 2024 Dec;78:103815. doi: 10.1016/j.breast.2024.103815. Epub 2024 Oct 15.

BACKGROUND

This paper aimed to evaluate the effectiveness of incorporating CDK 4/6 inhibitors (CDK4/6i) into ET for the adjuvant treatment of HR + HER2-resected early-stage breast cancer (ESBC) patients, employing meta-analysis.

METHODS

In this paper, we compiled randomized clinical trials focusing on CDK4/6i used in the adjuvant treatment of high-risk invasive HR-positive and HER2-ESBC patients. A meta-analysis was performed in line with the PRISMA guidelines.

RESULTS

We identified four clinical trials that met our inclusion criteria and were published between 2020 and 2024. These trials involved a combined sample size of 17,749 patients diagnosed with breast cancer. The data obtained from the pooled analysis revealed a remarkable beneficial trend in terms of invasive disease-free survival (iDFS) for the use of ET in combination with CDK4/6i compared to the group receiving ET alone (HR = 0.81, 95 % CI: 0.67-0.98, p = 0.03). Of note, CDK4/6 inhibitors demonstrated a notably beneficial effect in both grade 2 (HR = 0.69, 95 % CI: 0.59-0.81, p < 0.001) and grade 3 (HR = 0.76, 95 % CI: 0.65-0.89, p < 0.001). Significant improvements were noted in terms of distant relapse-free survival (dRFS) in the groups treated with abemaciclib and ribociclib (HR = 0.65, 95 % CI: 0.56-0.76, p < 0.001; HR = 0.72, 95 % CI: 0.58-0.89, p = 0.003, respectively). CDK4/6i didn't yield a statistically significant difference in overall survival (OS) (HR = 0.96, 95 % CI: 0.77-1.19, p = 0.69). The use of CDK4/6i with ET was associated with an increased risk of adverse events, particularly anemia and neutropenia, compared with ET alone (OR = 9.12, 95 % CI = 5.04-16.48, p < 0.001).

CONCLUSION

The findings of this paper demonstrate a significant improvement in iDFS when ET is combined with CDK4/6i, compared to ET alone. Specifically, treatments with abemaciclib and ribociclib showed notable enhancements in dRFS.

背景

本研究旨在通过荟萃分析评估 CDK4/6 抑制剂（CDK4/6i）联合 ET 用于 HR+HER2 早期乳腺癌（ESBC）辅助治疗的疗效。

方法

本研究纳入了 CDK4/6i 用于高危浸润性 HR 阳性和 HER2-ESBC 患者辅助治疗的随机临床试验。按照 PRISMA 指南进行荟萃分析。

结果

我们确定了四项符合纳入标准且发表于 2020 年至 2024 年的临床试验。这些试验共纳入了 17749 例乳腺癌患者。汇总分析的数据显示，与单独接受 ET 相比，ET 联合 CDK4/6i 治疗可显著改善浸润性无病生存（iDFS）（HR=0.81，95%CI：0.67-0.98，p=0.03）。值得注意的是，CDK4/6 抑制剂在 2 级（HR=0.69，95%CI：0.59-0.81，p<0.001）和 3 级（HR=0.76，95%CI：0.65-0.89，p<0.001）中均表现出显著获益。阿贝西利和瑞博西利治疗组的远处无复发生存（dRFS）也显著改善（HR=0.65，95%CI：0.56-0.76，p<0.001；HR=0.72，95%CI：0.58-0.89，p=0.003）。CDK4/6i 对总生存（OS）没有统计学意义（HR=0.96，95%CI：0.77-1.19，p=0.69）。与单独接受 ET 相比，ET 联合 CDK4/6i 治疗与不良事件风险增加相关，尤其是贫血和中性粒细胞减少（OR=9.12，95%CI=5.04-16.48，p<0.001）。