Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, Toronto, Ontario, Canada.
Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and the University of Toronto, Toronto, Ontario, Canada; Information Specialist, Library and Information Services, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Cancer Treat Rev. 2021 Nov;100:102283. doi: 10.1016/j.ctrv.2021.102283. Epub 2021 Aug 28.
The addition of platinum agents to anthracycline and taxane-based chemotherapy in early-stage triple negative breast cancer (TNBC) patients improves pathological complete response (pCR). Long-term outcomes, such as disease-free survival (DFS) and overall survival (OS), have not been well-established.
A systematic literature review identified studies using platinum-based treatment in TNBC patients in the neoadjuvant or adjuvant setting with reportable long-term outcomes. Hazard ratios (HR) from collected data were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on treatment setting and study design.
Fourteen studies comprising 3518 patients met the inclusion criteria. Median follow up was 56.2 months. All studies reported DFS and 9 studies (64%) reported OS. DFS was significantly better in platinum-based treatment (HR 0.71, 95% confidence interval (CI) 0.56-0.89; p = 0.03). However, OS was no different (HR 0.98, 95% CI 0.75-1.27; p = 0.87). There was a non-significant difference between platinum exposure in the adjuvant compared to neoadjuvant setting for both DFS (HR 0.75 vs 0.62, p = 0.43) and for OS (HR 0.90 vs 1.10, p = 0.58). The addition of platinum was associated with more thrombocytopenia and all-grade neuropathy and non-significant increases in neutropenia and grade 3-4 neuropathy.
Platinum-based treatment improves DFS but not OS. The reporting of toxicity was suboptimal, but in general adding platinum increased toxicity. The discordant effect of platinum-based treatment on DFS and OS suggest the potential development of platinum resistance and worse outcomes after recurrence. Platinum-based chemotherapy cannot be recommended in unselected patients with early TNBC.
在早期三阴性乳腺癌（TNBC）患者中，添加铂类药物联合蒽环类和紫杉烷类化疗可提高病理完全缓解率（pCR）。但长期结果，如无病生存（DFS）和总生存（OS），尚未得到充分证实。
系统文献回顾确定了使用含铂治疗方案治疗新辅助或辅助治疗的 TNBC 患者的研究，并报告了可报告的长期结果。使用通用逆方差和随机效应模型从收集的数据中进行荟萃分析，合并风险比（HR）。根据治疗方案和研究设计进行亚组分析。
14 项研究共纳入 3518 例患者，符合纳入标准。中位随访时间为 56.2 个月。所有研究均报告了 DFS，9 项研究（64%）报告了 OS。与单纯化疗相比，铂类药物治疗的 DFS 显著改善（HR 0.71，95%置信区间（CI）0.56-0.89；p=0.03）。然而，OS 无差异（HR 0.98，95%CI 0.75-1.27；p=0.87）。与新辅助治疗相比，辅助治疗中铂类药物暴露对 DFS（HR 0.75 与 0.62，p=0.43）和 OS（HR 0.90 与 1.10，p=0.58）的影响无显著差异。添加铂类药物与血小板减少症和所有级别的神经病变发生率增加相关，且中性粒细胞减少症和 3-4 级神经病变发生率略有增加，但无统计学意义。
铂类药物治疗可改善 DFS，但不能改善 OS。关于毒性的报告并不完善，但总体而言，添加铂类药物会增加毒性。铂类药物治疗对 DFS 和 OS 的不同影响提示可能发生铂类耐药和复发后结局较差。因此，不能推荐铂类化疗用于早期 TNBC 的未选择患者。
