CDK4/6抑制剂联合内分泌治疗对高风险侵袭性HR+/HER2-早期乳腺癌辅助治疗的疗效与安全性：一项全面的随机临床试验Meta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
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影响因子:7.9
分区:医学2区 / 妇产科学2区 肿瘤学2区
发表日期:2024 Dec
作者:
Merve Keskinkilic, Mehmet Emin Arayici, Yasemin Basbinar, Hulya Ellidokuz, Tugba Yavuzsen, Ilhan Oztop
DOI:
10.1016/j.breast.2024.103815
摘要
本文旨在评估将CDK4/6抑制剂（CDK4/6i）加入内分泌治疗（ET）以改善HR+、HER2-早期乳腺癌（ESBC）患者辅助治疗效果的有效性。本研究收集了针对高危侵袭性HR阳性和HER2-ESBC患者使用的CDK4/6i的随机临床试验，并按照PRISMA指南进行Meta分析。我们筛选出四项符合纳入标准、于2020年至2024年发表的临床试验，总样本量为17,749例乳腺癌患者。合并分析显示，联合内分泌治疗与CDK4/6i相比，单用ET在侵袭性无病生存期（iDFS）方面具有显著益处（HR=0.81，95% CI：0.67-0.98，p=0.03）。在2级和3级病理等级的患者中，CDK4/6抑制剂的效果尤为明显（HR=0.69，95% CI：0.59-0.81，p<0.001；HR=0.76，95% CI：0.65-0.89，p<0.001）。在远处复发无病生存期（dRFS）方面，使用阿贝西昔布（abemaciclib）和利莫昔芬（ribociclib）的组别均表现出显著改善（HR=0.65，95% CI：0.56-0.76，p<0.001；HR=0.72，95% CI：0.58-0.89，p=0.003）。总体生存期（OS）方面，CDK4/6i未表现出统计学显著差异（HR=0.96，95% CI：0.77-1.19，p=0.69）。与仅用ET相比，联合使用CDK4/6i增加了不良事件的风险，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）。本研究结果显示，联合CDK4/6i的ET显著改善了iDFS，特别是阿贝西昔布和利莫昔芬在dRFS方面表现出明显优势。
Abstract
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.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.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).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.