Isabella Michelon, Maria Inez Dacoregio, Maysa Vilbert, Jonathan Priantti, Caio Ernesto do Rego Castro, Lucas Vian, Paolo Tarantino, Evandro de Azambuja, Ludimila Cavalcante
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Nevertheless, antibody-drug conjugates (ADCs) have reshaped their prognosis.</p><p><strong>Objectives: </strong>We performed a systematic review and meta-analysis to assess the effectiveness of ADCs in patients with HER2-low advanced/metastatic (a/m) BC.</p><p><strong>Design: </strong>This study is a systematic review and meta-analysis.</p><p><strong>Data sources: </strong>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.</p><p><strong>Methods: </strong>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 <i>I</i> <sup>2</sup> test.</p><p><strong>Results: </strong>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 (<i>n</i> = 1691), followed by SG (<i>n</i> = 310), MRG002 (<i>n</i> = 56), and RC48-ADC (<i>n</i> = 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 (<i>n</i> = 1828, hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.36-0.68, <i>I</i> <sup>2</sup> = 82%, <i>p</i> < 0.001) and overall survival (<i>n</i> = 1546, HR 0.70, 95% CI 0.57-0.86, <i>I</i> <sup>2</sup> = 43%, <i>p</i> < 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, <i>I</i> <sup>2</sup> = 59%, <i>p</i> < 0.001), DCR (OR, 2.7, 95% CI 2.1-3.5, <i>I</i> <sup>2</sup> = 0%, <i>p</i> < 0.001), and CBR (OR, 3.6, 95% CI 2.6-5.2, <i>I</i> <sup>2</sup> = 56%, <i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>This study was registered in PROSPERO (CRD42024452962).</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"16 ","pages":"17588359241297079"},"PeriodicalIF":4.3000,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580099/pdf/","citationCount":"0","resultStr":"{\"title\":\"Antibody-drug conjugates in patients with advanced/metastatic HER2-low-expressing breast cancer: a systematic review and meta-analysis.\",\"authors\":\"Isabella Michelon, Maria Inez Dacoregio, Maysa Vilbert, Jonathan Priantti, Caio Ernesto do Rego Castro, Lucas Vian, Paolo Tarantino, Evandro de Azambuja, Ludimila Cavalcante\",\"doi\":\"10.1177/17588359241297079\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Until recently, targeted therapies have failed to benefit patients with human epidermal growth factor receptor 2 (HER2)-low-expressing breast cancer (BC). 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引用次数: 0
摘要
背景：直到最近，靶向疗法仍未能使人类表皮生长因子受体2（HER2）低表达乳腺癌（BC）患者获益。然而，抗体药物结合物（ADCs）重塑了患者的预后：我们进行了一项系统综述和荟萃分析，以评估 ADCs 对 HER2 低表达晚期/转移性（a/m）乳腺癌患者的疗效：本研究是一项系统综述和荟萃分析：我们检索了PubMed、Embase和Cochrane数据库以及美国临床肿瘤学会、欧洲肿瘤内科学会和圣安东尼奥乳腺癌研讨会会议论文集：方法：纳入对HER2低的a/mBC患者进行ADC（曲妥珠单抗德鲁司坦（T-DXd）、沙西珠单抗戈维替康（SG）、MRG002和RC48-ADC）评估的研究。我们使用 R 软件（v.4.2.2）和随机效应模型进行所有分析。异质性采用I 2检验进行评估：总共纳入了 14 项研究（5 项真实世界研究和 9 项临床试验 (CT)），共有 2883 例 HER2 低的 a/mBC 患者：其中808人接受了医生选择治疗（TPC），2075人接受了ADC治疗。大多数患者接受了T-DXd治疗（1691人），其次是SG（310人）、MRG002（56人）和RC48-ADC（18人）。接受T-DXd治疗的患者的客观反应率（ORR）、疾病控制率（DCR）和临床获益率（CBR）均明显高于接受其他ADC治疗的患者。在四项随机CT的汇总分析中，ADCs在统计学上延长了无进展生存期（n = 1828，危险比（HR）0.50，95%置信区间（CI）0.36-0.68，I 2 = 82%，p n = 1546，HR 0.70，95% CI 0.57-0.86，I 2 = 43%，p I 2 = 59%，p I 2 = 0%，p I 2 = 56%，p 结论：我们的系统综述和荟萃分析结果表明，ADCs能延长患者的无进展生存期：我们的系统综述和荟萃分析证实了 ADC 对 HER2 低 a/m BC 患者的疗效优于 TPC。未来的研究应侧重于将 ADCs 纳入这一人群的早期治疗方案：本研究已在 PROSPERO（CRD42024452962）注册。
Antibody-drug conjugates in patients with advanced/metastatic HER2-low-expressing breast cancer: a systematic review and meta-analysis.
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 I2 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 (n = 1691), followed by SG (n = 310), MRG002 (n = 56), and RC48-ADC (n = 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 (n = 1828, hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.36-0.68, I2 = 82%, p < 0.001) and overall survival (n = 1546, HR 0.70, 95% CI 0.57-0.86, I2 = 43%, p < 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, I2 = 59%, p < 0.001), DCR (OR, 2.7, 95% CI 2.1-3.5, I2 = 0%, p < 0.001), and CBR (OR, 3.6, 95% CI 2.6-5.2, I2 = 56%, p < 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).
期刊介绍：
Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
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