真相时刻——在三阴性乳腺癌的新辅助/辅助化疗中添加卡铂可提高总生存率：一项个体参与者数据和试验水平的荟萃分析。

Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis.

机构信息

Department of Medical Oncology, Dr. B.R.A.I.R.C.H, All India Institute of Medical Sciences, New Delhi, India.

Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Breast. 2022 Aug;64:7-18. doi: 10.1016/j.breast.2022.04.006. Epub 2022 Apr 15.

IMPORTANCE

Carboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial.

METHODS

The study was prospectively registered at PROSPERO (CRD42021228386). We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes.

RESULTS

Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44-3.08; I 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm.

CONCLUSION

and relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.

重要性

卡铂联合新辅助化疗可提高三阴性乳腺癌（TNBC）的病理完全缓解率（pCR），但关于其对生存结果的影响存在争议。

方法

该研究在 PROSPERO（CRD42021228386）前瞻性注册。我们系统地检索了 PubMed、Embase、Cochrane 临床对照试验中心注册库和会议论文集，以获取 2004 年 1 月 1 日至 2022 年 1 月 30 日有关 TNBC 患者（新）辅助化疗的相关随机临床试验（RCT）的相关信息，试验组采用卡铂，对照组采用标准蒽环类紫杉醇（AT）。本综述采用 PRISMA 指南。根据提取的风险比（HR），使用固定效应模型和随机效应模型适当汇总数据。从纳入 RCT 的已发表生存曲线中提取无病生存（DFS）和总生存（OS）的个体患者数据（IPD）；重建每个试验和联合人群的 DFS 和 OS 曲线，并估计 HR。主要结局是 DFS；OS、pCR 和毒性为次要结局。

结果

纳入了 8 项包含 2425 名患者的试验。与 AT 相比，卡铂在试验水平和 IPD 水平（HR 0.60；95%CI 0.47 至 0.78；I 45%，p<0.001）均改善了 DFS；在试验水平（HR 0.69，95%CI 0.50 至 0.95，I 41%，p=0.02）和 IPD 水平（HR 0.68；95%CI，0.54 至 0.87，p=0.002）分析中，OS 也得到了改善。卡铂组 pCR 也更好（OR 2.11；95%CI=1.44-3.08；I 67%，p=0.009）。卡铂组贫血和血小板减少症发生率较高。