PO.CL09.04 · 临床研究
基于CDK4/6抑制剂的方案与化疗在既往治疗过的HR+/HER2+转移性乳腺癌中的真实世界总生存与医疗资源利用：一项TriNetX全球协作网络分析
Real-world overall survival and healthcare utilization with CDK4/6 inhibitor based regimens versus chemotherapy in previously treated HR+/HER2+ metastatic breast cancer: A TriNetX Global Collaborative Network analysis
该海报暂无可下载的资料
AACR 官方页面
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：在II期monarcHER试验中，abemaciclib联合trastuzumab（联合或不联合内分泌治疗）相比化疗联合trastuzumab，改善了重度经治的激素受体阳性（HR+）/HER2+转移性乳腺癌的总生存（OS）。在此背景下，比较基于CDK4/6抑制剂的方案与化疗的可靠真实世界证据（RWE）仍然有限。
方法：我们利用TriNetX全球协作网络的去标识化电子健康记录开展一项回顾性队列研究，比较重度经治HR+/HER2+转移性乳腺癌成人患者中的两种方案：(1)CDK4/6抑制剂联合内分泌治疗和抗HER2治疗，(2)化疗联合抗HER2治疗。患者既往有抗HER2方案暴露，但无明确的进展事件和治疗线数记录。主要终点为总生存（OS），随访至1200天；次要终点包括中性粒细胞减少、心力衰竭（作为心脏毒性的替代指标）和急诊科（ED）就诊。采用倾向评分匹配（1:1）以平衡各队列的人口统计学和合并症。采用Kaplan-Meier方法、log-rank检验和Cox比例风险模型估算生存概率和风险比（HR）。
结果：PSM后每个队列140例患者，基线平衡。化疗组中位随访573天，CDK4/6抑制剂治疗组479天。在1200天内，化疗队列死亡率为36.4%（51/140），CDK4/6抑制剂队列为17.1%（24/140），绝对风险降低19.3%（95% CI，9.2-29.4），倾向于CDK4/6抑制剂。在1200天内，基于CDK4/6抑制剂的方案相比化疗显著降低了死亡风险（HR，0.52；95% CI，0.32-0.84；p=0.007）。中性粒细胞减少和心力衰竭相似，但ED就诊在化疗组更频繁（HR 1.59；p=0.012）。
结论：在这项针对既往治疗过的HR+/HER2+转移性乳腺癌的真实世界倾向匹配分析中，基于CDK4/6抑制剂的内分泌和抗HER2治疗在1200天窗口内与显著更低的死亡风险（HR 0.52；绝对风险降低19.3%）和减少的ED利用相关，相比化疗联合抗HER2治疗。尽管存在回顾性、非随机真实世界证据的局限性，这些发现支持monarcHER中观察到的OS获益，并强化了靶向内分泌策略作为重度经治HR+/HER2+转移性乳腺癌中化疗的临床相关替代方案。
查看英文原文 English abstract
Background: In the phase II monarcHER trial, abemaciclib plus trastuzumab with or without endocrine therapy improved overall survival (OS) versus chemotherapy plus trastuzumab in heavily pretreated hormone receptor-positive (HR+)/HER2+ metastatic breast cancer. Robust real-world evidence (RWE) comparing CDK4/6 inhibitor-based regimens with chemotherapy in this setting remains limited.
Methods: We conducted a retrospective cohort study using de-identified electronic health records from the TriNetX Global Collaborative Network to compare two regimens in adults with highly pretreated HR+/HER2+ metastatic breast cancer: (1) CDK4/6 inhibitor plus endocrine and anti-HER2 therapy, and (2) chemotherapy plus anti-HER2 therapy. Prior exposure to anti-HER2 regimens was present, but explicit progression events and line counts were unavailable. The primary endpoint was overall survival (OS) up to 1200 days; secondary endpoints included neutropenia, heart failure (as a proxy for cardiotoxicity), and emergency department (ED) visits. Propensity score matching (1:1) was used to balance cohorts on demographics and comorbidities. Survival probabilities and hazard ratios (HRs) were estimated using Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models.
Results: PSM resulted in 140 patients per cohort with balanced baselines. Median follow-up was 573 days for chemotherapy and 479 days for CDK4/6 inhibitor therapy. Over 1200 days, death occurred in 36.4% (51/140) of the chemotherapy cohort and 17.1% (24/140) of the CDK4/6 inhibitor cohort, a 19.3% absolute risk reduction (95% CI, 9.2-29.4) favoring CDK4/6 inhibitors. Over the 1200-day, CDK4/6 inhibitor-based regimens significantly lowered the hazard of death compared to chemotherapy (HR, 0.52; 95% CI, 0.32-0.84; p=0.007). Neutropenia and heart failure were similar, but ED visits were more frequent with chemotherapy (HR 1.59; p=0.012).
Conclusions: In this real-world, propensity-matched analysis of previously treated HR+/HER2+ metastatic breast cancer, CDK4/6 inhibitor-based endocrine and anti-HER2 therapy was associated with substantially lower mortality risk (HR 0.52; 19.3% absolute risk reduction) and reduced ED utilization compared with chemotherapy plus anti-HER2 therapy over a 1200-day window. These findings support the OS benefit seen in monarcHER and reinforce targeted endocrine strategies as clinically relevant alternatives to chemotherapy in heavily pretreated HR+/HER2+ metastatic breast cancer, despite the limitations of retrospective, non-randomized real-world evidence.
利益披露 Disclosure
M. Eysha, None..
U. Hussain, None..
M. Elchouemi, None..
M. Black, None..
S. Siby, None..
W. Zhang, None..
A. Asad, None.