Systematic Review and Network Meta-Analysis on Treating Hormone Receptor-Positive Metastatic Breast Cancer After CDK4/6 Inhibitors.

IF 3.4 4区医学 Q2 ONCOLOGY Current oncology Pub Date : 2025-01-20 DOI:10.3390/curroncol32010053

Neha Pathak, Abhenil Mittal, Sudhir Kumar, Chitrakshi Nagpal, Eitan Amir, Partha Haldar, Bharath B Gangadharaiah, Akash Kumar, Ashutosh Mishra, Atul Batra

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Abstract

Introduction: The optimal treatment of estrogen receptor-positive (ER +) metastatic breast cancer (MBC) after progression on cyclin-dependent 4/6 kinase inhibitors (CDK4/6i) is unknown.

Methods: We conducted a systematic review and network meta-analysis (NMA) of phase-II/-III randomized trials of ER + MBC post CDK4/6i + ET progression. We calculated the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) using generic inverse variance and odds ratios (ORs) using the Mantel-Haenszel method for adverse events (AEs) with Review-Manager version-5.4. NMA was executed using WINBUGS (Microsoft Excel). Three molecular subgroups were analyzed: HER2-low, PI3K/AKT/mTOR, and the ESR1 mutation subgroup for selective estrogen receptor degrader (SERD).

Results: A total of 14 studies were included. In the HER2-low group, Sacituzumab govitecan and trastuzumab deruxtecan had a similar efficacy (HR, 95% CI): PFS (0.98; 0.63-1.43) and OS (1.08; 0.76-1.55). In PI3K/AKT/mTOR-altered cases, capivasertib was superior to alpelisib PFS (0.77; 0.53-1.12), and OS (0.80; 0.48-1.35). SERDs had worse PFS and OS versus ongoing CDK 4/6i (ribociclib).

Conclusion: No therapy emerged as the unequivocal choice in the post-CDK 4/6i domain in unselected subgroups. In the HER2-low population, a similar efficacy and different toxicity spectrum was seen. In AKT-altered tumors, capivasertib was less toxic than alpelisib.

Prospero id: CRD4202236412.

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CDK4/6抑制剂治疗激素受体阳性转移性乳腺癌的系统评价和网络meta分析

引言：雌激素受体阳性（ER +）转移性乳腺癌（MBC）在使用周期蛋白依赖的4/6激酶抑制剂（CDK4/6i）进展后的最佳治疗方法尚不清楚。方法：我们对CDK4/6i + ET进展后ER + MBC的ii /-III期随机试验进行了系统回顾和网络荟萃分析（NMA）。我们使用Review-Manager version-5.4使用Mantel-Haenszel方法计算无进展生存期（PFS）和总生存期（OS）的风险比（HR），使用通用逆方差和优势比（ORs）计算不良事件（ae）。NMA使用WINBUGS （Microsoft Excel）执行。分析三个分子亚组：HER2-low， PI3K/AKT/mTOR和选择性雌激素受体降解物（SERD）的ESR1突变亚组。结果：共纳入14项研究。在her2低组中，舒妥珠单抗govitecan和曲妥珠单抗deruxtecan具有相似的疗效（HR, 95% CI）： PFS (0.98；0.63-1.43)和OS (1.08；0.76 - -1.55)。在PI3K/AKT/ mtor改变的病例中，capivasertib优于alpelisib PFS (0.77；0.53-1.12), OS (0.80；0.48 - -1.35)。与正在进行的CDK 4/6i （ribociclib）相比，serd的PFS和OS更差。结论：在未选择的亚组中，没有治疗成为cdk4 /6i后结构域的明确选择。在her2低人群中，观察到相似的疗效和不同的毒性谱。在akt改变的肿瘤中，capivasertib的毒性低于alpelisib。普洛斯彼罗id: CRD4202236412。

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来源期刊

Current oncology ONCOLOGY-

CiteScore

3.30

自引率

7.70%

发文量

664

审稿时长

1 months

期刊介绍： Current Oncology is a peer-reviewed, Canadian-based and internationally respected journal. Current Oncology represents a multidisciplinary medium encompassing health care workers in the field of cancer therapy in Canada to report upon and to review progress in the management of this disease. We encourage submissions from all fields of cancer medicine, including radiation oncology, surgical oncology, medical oncology, pediatric oncology, pathology, and cancer rehabilitation and survivorship. Articles published in the journal typically contain information that is relevant directly to clinical oncology practice, and have clear potential for application to the current or future practice of cancer medicine.