目的:细胞周期蛋白依赖性激酶(CDK)4/6抑制剂显着改变了激素阳性(HR)的治疗前景,HER2-转移性乳腺癌(MBC)。然而,预测长期获益和早期进展的生物标志物尚待确定.一些研究表明,低HER2患者的疗效可能降低。因此,我们进行了系统评价和荟萃分析,以评估低水平HER2表达与疗效结局之间的关联(PFS,操作系统,ORR)与CDK4/6抑制剂。
方法:发布,WebofScience,和Scopus数据库用于系统地过滤从开始到2023年8月8日的已发表研究,以进行本系统综述。包括使用CDK4/6抑制剂治疗的MBC患者的研究以及根据HER2表达报告的生存结果。我们使用固定效应模型的通用逆方差方法进行了荟萃分析,并使用具有95%双边CI的HR作为主要摘要度量。
结果:包括2705名患者在内的9项研究被纳入分析。在九项研究的汇总分析中,与HER2-0相比,低HER2肿瘤患者的进展和/或死亡风险更高(HR:1.22,95%CI1.10~1.35,p<0.001).在五项研究的汇总分析中,尽管中位随访时间很短,HER2低组的死亡风险高于HER2零组(HR:1.22,95%CI1.04~1.44,p=0.010).
结论:现有证据表明,CDK4/6抑制剂在低HER2肿瘤中的进展或死亡风险显著增高。需要进一步的研究来改善HR+-HER2低肿瘤患者的预后。
OBJECTIVE: The cyclin-dependent kinase (CDK) 4/6 inhibitors significantly altered the treatment landscape of hormone-positive (HR+), HER2- metastatic breast cancer (MBC). However, biomarkers predicting long-term benefit and early progression are yet to be defined. Several studies suggested the possibility of diminished efficacy in patients with HER2-low disease. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between low-level HER2 expression and efficacy outcomes (PFS, OS, ORR) with CDK 4/6 inhibitors.
METHODS: The Pubmed, Web of Science, and Scopus databases were used to systematically filter the published studies from inception to 08 August 2023 for this systemic review. Studies including MBC patients treated with CDK 4/6 inhibitors and reported survival outcomes according to HER2 expression were included. We performed the meta-analyses with the generic inverse-variance method with a fixed-effects model and used HRs with 95% two-sided CIs as the principal summary measure.
RESULTS: Nine studies encompassing 2705 patients were included in the analyses. In the pooled analysis of nine studies, the risk of progression and/or death was higher in patients with HER2-low tumors compared to HER2-zero (HR: 1.22, 95% CI 1.10-1.35, p < 0.001). In the pooled analysis of five studies, although the median follow-up was short, the risk of death was higher in the HER2-low group compared to the HER2-zero group (HR: 1.22, 95% CI 1.04-1.44, p = 0.010).
CONCLUSIONS: The available evidence demonstrates a significantly higher risk of progression or death with CDK 4/6 inhibitors in HER2-low tumors. Further research is needed to improve outcomes in patients with HR+-HER2-low tumors.