三阴性乳腺癌的含铂新辅助化疗：系统评价和荟萃分析。
Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis.
机构信息
Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Department of Medical Oncology, Oncologia Medica 2, School of Medicine, University of Genova, Genova, Italy.
Unit of Clinical Epidemiology, School of Medicine, University of Genova, Genova, Italy.
出版信息
Ann Oncol. 2018 Jul 1;29(7):1497-1508. doi: 10.1093/annonc/mdy127.
BACKGROUND
The role of platinum-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients is highly controversial and it is not endorsed by current guidelines. Our meta-analysis aimed to better elucidate its activity, efficacy and safety.
MATERIAL AND METHODS
A systematic search of Medline, Web of Science and conferences proceedings up to 30 October 2017 was carried out to identify randomized controlled trials (RCTs) investigating platinum-based versus platinum-free neoadjuvant chemotherapy in TNBC patients. Using the fixed and random effects models, pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CI) were calculated for pathological complete response (pCR, defined as ypT0/is pN0), event-free survival (EFS), overall survival (OS) and grade 3 and 4 adverse events (AEs: neutropenia, anemia, thrombocytopenia and neuropathy).
RESULTS
Nine RCTs (N = 2109) were included. Overall, platinum-based neoadjuvant chemotherapy significantly increased pCR rate from 37.0% to 52.1% (OR 1.96, 95% CI 1.46-2.62, P < 0.001). Platinum-based neoadjuvant chemotherapy remained significantly associated with increased pCR rate also after restricting the analysis to the three RCTs (N = 611) that used the same standard regimen in both groups of weekly paclitaxel (with or without carboplatin) followed by anthracycline and cyclophosphamide (OR 2.53, 95% CI 1.37-4.66, P = 0.003). Conversely, among the 96 BRCA-mutated patients included in two RCTs, the addition of carboplatin was not associated with significantly increased pCR rate (OR 1.17, 95% CI 0.51-2.67, P = 0.711). Two RCTs (N = 748) reported survival outcomes: no significant difference in EFS (HR 0.72, 95% CI 0.49-1.06, P = 0.094) and OS (HR 0.86, 95% CI 0.46-1.63, P = 0.651) was observed. A significant higher risk of grade 3 and 4 hematological AEs, with no increased risk of grade 3 and 4 neuropathy was observed with platinum-based neoadjuvant chemotherapy.
CONCLUSION
In TNBC patients, platinum-based neoadjuvant chemotherapy is associated with significantly increased pCR rates at the cost of worse hematological toxicities. Platinum-based neoadjuvant chemotherapy may be considered an option in TNBC patients.
PROSPERO REGISTRATION NUMBER
CRD42018080042.
背景
铂类新辅助化疗在三阴性乳腺癌（TNBC）患者中的作用存在争议，目前的指南并不支持这种治疗方法。我们的荟萃分析旨在更好地阐明其活性、疗效和安全性。
材料与方法
对 Medline、Web of Science 和会议记录进行系统检索，以确定截至 2017 年 10 月 30 日调查 TNBC 患者中铂类与非铂类新辅助化疗的随机对照试验（RCT）。使用固定效应模型和随机效应模型，计算病理完全缓解（ypT0/is pN0 定义）、无事件生存（EFS）、总生存（OS）和 3 级和 4 级不良事件（AE：中性粒细胞减少症、贫血、血小板减少症和神经病变）的合并优势比（OR）和风险比（HR）。
结果
纳入 9 项 RCT（N=2109）。总体而言，铂类新辅助化疗可显著提高 pCR 率（从 37.0%提高至 52.1%）（OR 1.96，95%置信区间 1.46-2.62，P<0.001）。在限制分析仅纳入 3 项 RCT（N=611）后，铂类新辅助化疗仍与 pCR 率的显著提高相关，这些 RCT 两组均使用每周紫杉醇（联合或不联合卡铂）继以蒽环类药物和环磷酰胺的相同标准方案（OR 2.53，95%置信区间 1.37-4.66，P=0.003）。相反，在纳入两项 RCT（N=96）的 96 例 BRCA 突变患者中，加用卡铂并不能显著提高 pCR 率（OR 1.17，95%置信区间 0.51-2.67，P=0.711）。两项 RCT（N=748）报告了生存结局：EFS（HR 0.72，95%置信区间 0.49-1.06，P=0.094）和 OS（HR 0.86，95%置信区间 0.46-1.63，P=0.651）无显著差异。铂类新辅助化疗可导致更高的 3 级和 4 级血液学 AE 风险，但无 3 级和 4 级神经病变风险增加。
结论
在 TNBC 患者中，铂类新辅助化疗可显著提高 pCR 率，但代价是更严重的血液学毒性。铂类新辅助化疗可能是 TNBC 患者的一种选择。
PROSPERO 注册号：CRD42018080042。
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