Dacoregio Maria Inez, Michelon Isabella, Ernesto do Rego Castro Caio, Cezar Aquino de Moraes Francisco, Rossato de Almeida Guilherme, Ravani Lis Victória, Vilbert Maysa, Barros Costa Ricardo Lima
Department of Medicine, University of Centro Oeste, Guarapuava, Brazil.
Department of Medicine, Catholic University of Pelotas, Pelotas, Brazil.
Breast. 2025 Feb;79:103853. doi: 10.1016/j.breast.2024.103853. Epub 2024 Nov 23.
Sacituzumab Govitecan (SG), a first-in-class anti-trophoblast cell surface antigen-2-directed antibody-drug conjugate (ADC), has shown clinically meaningful improvement in outcomes of patients with breast cancer (BC). However, it has also been accompanied by significant toxicity. Thus, we conducted a systematic review and meta-analysis to evaluate the safety and tolerability of SG in this patient population.
We comprehensively searched PubMed, Embase, and Cochrane databases, and ASCO and ESMO websites for clinical trials (CTs) assessing the safety of SG in BC patients. All analyses were performed in R software (v.4.2.2) using random effects models. Heterogeneity was assessed using I test.
Seven studies - three randomized clinical trials (RCTs) and four single-arm phase I/II - were included, comprising 928 patients receiving SG and 576 on treatment of physician's choice (TPC). Most patients had triple negative BC (54.4 %, n = 505), metastatic disease (89.8 %, n = 833), and were heavily pretreated (at least two lines of prior therapy). Most common all-grade adverse events (AEs) were: neutropenia (70 %, 95 % CI, 64-76 %), followed by nausea (62 %, 95 % CI, 55-68 %), diarrhea (54 %, 95 % CI 47-60 %) and anemia (51 %, 95 % CI, 38-65 %). Regarding high-grade AEs, 46 % of patients developed grade ≥3 neutropenia. Compared to TPC, we observed a higher risk of neutropenia (OR 3.11, 95 % CI 1.62-5.99, I = 81 %; p < 0.001), diarrhea (OR 6.82, 95 % CI 3.99-11.66, I = 64 %; p < 0.001) and anemia (OR 2.26, 95 % CI 1.20-4.27, I = 78 %; p = 0.012) for those on SG. Dose reductions and treatment discontinuation were reported in 22 % and 4 % of patients, respectively, and 19 deaths (2 %) were documented. Most of them were not deemed to be treated-related.
This systematic review and meta-analysis provides extensive data on the safety and management of SG toxicity in BC patients across clinical trials. Concerning rates of neutropenia, nausea diarrhea, and anemia were reported. We highlight the need for protocols establishing prophylactic measures and strategies to mitigate SG-related toxicity.
戈沙妥珠单抗（SG）是首个靶向滋养层细胞表面抗原2的抗体药物偶联物（ADC），已在乳腺癌（BC）患者的治疗中显示出具有临床意义的疗效改善。然而，它也伴随着显著的毒性。因此，我们进行了一项系统评价和荟萃分析，以评估SG在该患者群体中的安全性和耐受性。
我们全面检索了PubMed、Embase和Cochrane数据库以及美国临床肿瘤学会（ASCO）和欧洲肿瘤内科学会（ESMO）网站，以查找评估SG在BC患者中安全性的临床试验（CT）。所有分析均使用R软件（v.4.2.2）中的随机效应模型进行。使用I²检验评估异质性。
纳入了7项研究——3项随机临床试验（RCT）和4项单臂I/II期研究，共928例接受SG治疗的患者和576例接受医生选择治疗（TPC）的患者。大多数患者患有三阴性乳腺癌（54.4%，n = 505）、转移性疾病（89.8%，n = 833），并且接受过大量预处理（至少两线既往治疗）。最常见的所有级别的不良事件（AE）为：中性粒细胞减少（70%，95%CI，64 - 76%），其次是恶心（62%，95%CI，55 - 68%）、腹泻（54%，95%CI 47 - 60%）和贫血（51%，95%CI，38 - 65%）。关于高级别AE，46%的患者发生≥3级中性粒细胞减少。与TPC相比，我们观察到接受SG治疗的患者发生中性粒细胞减少（OR 3.11，95%CI 1.62 - 5.99，I² = 81%；p < 0.001）、腹泻（OR 6.82，95%CI 3.99 - 11.66，I² = 64%；p < 0.001）和贫血（OR 2.26，95%CI 1.20 - 4.27，I² = 78%；p = 0.012）的风险更高。分别有22%和4%的患者报告剂量减少和治疗中断，并记录了19例死亡（2%）。其中大多数死亡不被认为与治疗相关。
这项系统评价和荟萃分析提供了关于SG在BC患者中的安全性和毒性管理的广泛数据，报告了中性粒细胞减少、恶心、腹泻和贫血的发生率。我们强调需要制定建立预防措施和策略以减轻SG相关毒性的方案。
