Abstract：
BACKGROUND: There are multiple neoadjuvant regimens, including platinum agents for triple-negative breast cancer (TNBC), each with a different safety profile, outcome, and pathologic complete response rate (pCR%). We performed a systematic review and network meta-analysis to compare the efficacy and safety of different platinum-based neoadjuvant CT treatments for TNBC.
METHODS: Bibliographic databases (PubMed, Embase, and Cochrane Library) were searched from their inception to October 31, 2022. Eligible studies were randomized clinical trials that evaluated the addition of carboplatin or cisplatin to standard neoadjuvant CT for TNBC. The primary endpoints were pCR rates and DFS/EFS, while the secondary endpoints were grade (G)3-4 hematological toxicity and OS.
RESULTS: Thirteen trials involving 3154 patients comparing six treatments (carboplatin AUC 5, carboplatin AUC 6, carboplatin AUC 2, carboplatin AUC 1.5, cisplatin 75 mg/m2, and standard anthracycline-and/or taxane-based CT) were identified. Based on the most effective treatments added to neoadjuvant CT, carboplatin AUC 2 was associated with the least improvement in pCR% (RR, 1.49; 95%CI, 1.23, 1.8), carboplatin AUC 6 was associated with similar improvement in pCR% (RR 1.58, 95%CI, 1.35, 1.84) and carboplatin AUC 5 with the highest improvement in pCR% (RR 2.23, 95%CI, 1.6,32). The treatment associated with the most considerable improvement in DFS when added to neoadjuvant CT was carboplatin AUC 5 (HR 0.36, 95%CI 0.18, 0.73). It was also better than AUC 6 and AUC 2 (HR= 0.45, 95%CI 0.21-0.96 and HR=0.48, 95%CI 0.23-0.98). All schedules exhibited similar outcomes in terms of OS; however, only AUC 2 demonstrated a significant improvement compared to the no-platinum arms. Neutropenia, thrombocytopenia, and anemia G3-4 were significantly increased by carboplatin AUC 6.
CONCLUSIONS: Based on this network meta-analysis, carboplatin AUC 5 added to standard neoadjuvant CT may provide substantial pCR and DFS benefits with a low toxicity risk compared to other carboplatin doses.
METHODS: Bibliographic databases (PubMed, Embase, and Cochrane Library) were searched from their inception to October 31, 2022. Eligible studies were randomized clinical trials that evaluated the addition of carboplatin or cisplatin to standard neoadjuvant CT for TNBC. The primary endpoints were pCR rates and DFS/EFS, while the secondary endpoints were grade (G)3-4 hematological toxicity and OS.
RESULTS: Thirteen trials involving 3154 patients comparing six treatments (carboplatin AUC 5, carboplatin AUC 6, carboplatin AUC 2, carboplatin AUC 1.5, cisplatin 75 mg/m2, and standard anthracycline-and/or taxane-based CT) were identified. Based on the most effective treatments added to neoadjuvant CT, carboplatin AUC 2 was associated with the least improvement in pCR% (RR, 1.49; 95%CI, 1.23, 1.8), carboplatin AUC 6 was associated with similar improvement in pCR% (RR 1.58, 95%CI, 1.35, 1.84) and carboplatin AUC 5 with the highest improvement in pCR% (RR 2.23, 95%CI, 1.6,32). The treatment associated with the most considerable improvement in DFS when added to neoadjuvant CT was carboplatin AUC 5 (HR 0.36, 95%CI 0.18, 0.73). It was also better than AUC 6 and AUC 2 (HR= 0.45, 95%CI 0.21-0.96 and HR=0.48, 95%CI 0.23-0.98). All schedules exhibited similar outcomes in terms of OS; however, only AUC 2 demonstrated a significant improvement compared to the no-platinum arms. Neutropenia, thrombocytopenia, and anemia G3-4 were significantly increased by carboplatin AUC 6.
CONCLUSIONS: Based on this network meta-analysis, carboplatin AUC 5 added to standard neoadjuvant CT may provide substantial pCR and DFS benefits with a low toxicity risk compared to other carboplatin doses.
摘要：
背景：有多种新辅助治疗方案，包括用于三阴性乳腺癌（TNBC）的铂类药物，每个都有不同的安全特征，结果,病理完全缓解率(pCR%)。我们进行了系统评价和网络荟萃分析，以比较不同铂类新辅助CT治疗TNBC的疗效和安全性。
方法：书目数据库(PubMed，Embase,和Cochrane图书馆）从成立之初到2022年10月31日进行了搜索。符合条件的研究是随机临床试验，评估了在TNBC的标准新辅助CT中添加卡铂或顺铂。主要终点是pCR率和DFS/EFS，次要终点是（G）3-4级血液学毒性和OS。
结果：确定了13项试验，涉及3154例患者，比较了6种治疗方法（卡铂AUC5，卡铂AUC6，卡铂AUC2，卡铂AUC1.5，顺铂75mg/m2和标准蒽环类和/或紫杉烷的CT）。基于新辅助CT最有效的治疗方法，卡铂AUC2与pCR%改善最小(RR，1.49;95CI,1.23,1.8),卡铂AUC6与pCR%改善相似(RR1.58,95CI,1.35,1.84),卡铂AUC5与pCR%改善最高(RR2.23,95CI,1.6,32).当添加到新辅助CT时，与DFS最显著改善相关的治疗是卡铂AUC5（HR0.36，95CI0.18，0.73）。它也优于AUC6和AUC2（HR=0.45，95CI0.21-0.96和HR=0.48，95CI0.23-0.98）。所有时间表在操作系统方面都表现出相似的结果；然而，与无铂臂相比，只有AUC2表现出显着改善。中性粒细胞减少症,血小板减少症,卡铂AUC6显著增加贫血G3-4。
结论：基于此网络荟萃分析，与其他卡铂剂量相比,标准新辅助CT中添加卡铂AUC5可提供显著的pCR和DFS获益,且毒性风险较低.
方法：书目数据库(PubMed，Embase,和Cochrane图书馆）从成立之初到2022年10月31日进行了搜索。符合条件的研究是随机临床试验，评估了在TNBC的标准新辅助CT中添加卡铂或顺铂。主要终点是pCR率和DFS/EFS，次要终点是（G）3-4级血液学毒性和OS。
结果：确定了13项试验，涉及3154例患者，比较了6种治疗方法（卡铂AUC5，卡铂AUC6，卡铂AUC2，卡铂AUC1.5，顺铂75mg/m2和标准蒽环类和/或紫杉烷的CT）。基于新辅助CT最有效的治疗方法，卡铂AUC2与pCR%改善最小(RR，1.49;95CI,1.23,1.8),卡铂AUC6与pCR%改善相似(RR1.58,95CI,1.35,1.84),卡铂AUC5与pCR%改善最高(RR2.23,95CI,1.6,32).当添加到新辅助CT时，与DFS最显著改善相关的治疗是卡铂AUC5（HR0.36，95CI0.18，0.73）。它也优于AUC6和AUC2（HR=0.45，95CI0.21-0.96和HR=0.48，95CI0.23-0.98）。所有时间表在操作系统方面都表现出相似的结果；然而，与无铂臂相比，只有AUC2表现出显着改善。中性粒细胞减少症,血小板减少症,卡铂AUC6显著增加贫血G3-4。
结论：基于此网络荟萃分析，与其他卡铂剂量相比,标准新辅助CT中添加卡铂AUC5可提供显著的pCR和DFS获益,且毒性风险较低.
