晚期/转移性HER2低表达乳腺癌患者的抗体药物偶联物：一项系统评价和荟萃分析
Antibody-drug conjugates in patients with advanced/metastatic HER2-low-expressing breast cancer: a systematic review and meta-analysis.
作者信息
Michelon Isabella, Dacoregio Maria Inez, Vilbert Maysa, Priantti Jonathan, do Rego Castro Caio Ernesto, Vian Lucas, Tarantino Paolo, de Azambuja Evandro, Cavalcante Ludimila
机构信息
Department of Medicine, Catholic University of Pelotas, 373 Gonçalves Chaves, Pelotas 96010-000, Brazil.
Department of Medicine, University of Centro Oeste, Guarapuava, Brazil.
出版信息
Ther Adv Med Oncol. 2024 Nov 20;16:17588359241297079. doi: 10.1177/17588359241297079. eCollection 2024.
BACKGROUND
Until recently, targeted therapies have failed to benefit patients with human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC). Nevertheless, antibody-drug conjugates (ADCs) have reshaped their prognosis.
OBJECTIVES
We performed a systematic review and meta-analysis to assess the effectiveness of ADCs in patients with HER2-low advanced/metastatic (a/m) BC.
DESIGN
This study is a systematic review and meta-analysis.
DATA SOURCES
We searched PubMed, Embase, and Cochrane databases as well as the American Society of Clinical Oncology, European Society for Medical Oncology, and San Antonio Breast Cancer Symposium conference proceedings.
METHODS
Studies evaluating ADCs (trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), MRG002, and RC48-ADC) in patients with HER2-low a/mBC were included. We used R software (v.4.2.2) and random effects models for all analyses. Heterogeneity was assessed using the test.
RESULTS
Overall, 14 studies were included (five real-world studies and nine clinical trials (CTs)), with 2883 HER2-low a/mBC patients: 808 received treatment of physician's choice (TPC), and 2075 ADCs. Most were treated with T-DXd ( = 1691), followed by SG ( = 310), MRG002 ( = 56), and RC48-ADC ( = 18). Patients treated with T-DXd achieved a significantly higher objective response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR) than those receiving other ADCs. In the pooled analysis of four randomized CTs, ADCs statistically prolonged progression-free survival ( = 1828, hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.36-0.68, = 82%, < 0.001) and overall survival ( = 1546, HR 0.70, 95% CI 0.57-0.86, = 43%, < 0.001) compared with TPC. Patients on ADCs also achieved a greater antitumor response than TPC, including better ORR (odds ratio (OR), 3.7, 95% CI 2.5-5.6, = 59%, < 0.001), DCR (OR, 2.7, 95% CI 2.1-3.5, = 0%, < 0.001), and CBR (OR, 3.6, 95% CI 2.6-5.2, = 56%, < 0.01).
CONCLUSION
Our systematic review and meta-analysis confirms the efficacy of ADCs in HER2-low a/m BC patients over TPC. Future studies should focus on bringing ADCs into earlier lines of therapy in this population.
TRIAL REGISTRATION
This study was registered in PROSPERO (CRD42024452962).
背景
直到最近，靶向治疗未能使人类表皮生长因子受体2（HER2）低表达乳腺癌（BC）患者受益。然而，抗体药物偶联物（ADC）改变了他们的预后。
目的
我们进行了一项系统评价和荟萃分析，以评估ADC在HER2低表达晚期/转移性（a/m）BC患者中的有效性。
设计
本研究为系统评价和荟萃分析。
数据来源
我们检索了PubMed、Embase和Cochrane数据库以及美国临床肿瘤学会、欧洲医学肿瘤学会和圣安东尼奥乳腺癌研讨会会议记录。
方法
纳入评估ADC（曲妥珠单抗德曲妥珠单抗（T-DXd）、戈沙妥珠单抗（SG）、MRG002和RC48-ADC）治疗HER2低表达a/mBC患者的研究。我们使用R软件（v.4.2.2）和随机效应模型进行所有分析。使用 检验评估异质性。
结果
总体而言，纳入了14项研究（5项真实世界研究和9项临床试验（CT）），共2883例HER2低表达a/mBC患者：808例接受了医生选择的治疗（TPC），2075例接受了ADC治疗。大多数患者接受T-DXd治疗（=1691），其次是SG（=310）、MRG002（=56）和RC48-ADC（=18）。接受T-DXd治疗的患者比接受其他ADC治疗的患者获得了显著更高的客观缓解率（ORR）、疾病控制率（DCR）和临床获益率（CBR）。在四项随机CT的汇总分析中，与TPC相比，ADC在统计学上延长了无进展生存期（=1828，风险比（HR）0.50，95%置信区间（CI）0.36-0.68， =82%， <0.001）和总生存期（=1546，HR 0.70，95%CI 0.57-0.86， =43%， <0.001）。接受ADC治疗的患者也比TPC获得了更大的抗肿瘤反应，包括更好的ORR（优势比（OR），3.7，95%CI 2.5-5.6， =59%， <0.001）、DCR（OR，2.7，95%CI 2.1-3.5， =0%， <0.001）和CBR（OR，3.6，95%CI 2.6-5.2， =56%， <0.01）。
结论
我们的系统评价和荟萃分析证实了ADC在HER2低表达a/m BC患者中优于TPC的疗效。未来的研究应侧重于将ADC引入该人群的更早期治疗线。
试验注册
本研究在PROSPERO（CRD42024452962）注册。
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