从特殊人群角度看新辅助免疫检查点抑制剂联合化疗在乳腺癌中的疗效与安全性：一项系统评价与荟萃分析
Efficacy and safety of neoadjuvant ICI combined with chemotherapy in breast cancer from the perspective of a privileged population: a systematic review and meta-analysis.
作者信息
Liu Shiyang, Li Xiang, Wu Chen, Yao Litong, Dong Haoran, Zhang Hengjun, Wang Yusong, Wang Mozhi, Xu Yingying
机构信息
Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning Province 110001, PR China.
Department of Ultrasound, The First Hospital of China Medical University, Shenyang, Liaoning Province 110001, PR China.
出版信息
Int J Surg. 2025 Jul 1;111(7):4726-4735. doi: 10.1097/JS9.0000000000002528. Epub 2025 May 26.
PURPOSE
This study evaluates the effectiveness and safety of immune checkpoint inhibitors (ICIs) with chemotherapy for various breast cancer subtypes and assesses neoadjuvant immunotherapy benefits based on lymph node and chemo-backbone statuses.
METHODS
We systematically reviewed randomized controlled trials (RCTs) from PubMed, EMBASE, the Cochrane Library, and oncology conferences involving PD-1/PD-L1 inhibitors with chemotherapy as neoadjuvant therapy for breast cancer. Endpoints were pathological complete response (pCR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Odds ratios (OR), hazard ratios (HR), and 95% confidence intervals (CI) were extracted for meta-analysis using Review Manager (version 5.4).
RESULTS
Analysis of 3739 patients from eight RCTs showed that ICIs combined with chemotherapy significantly improved pCR (OR = 0.61, 95% CI: 0.48-0.77, P = 0.0005), EFS (HR = 0.72, 95% CI: 0.59-0.87, P = 0.0008), and OS (HR = 0.63, 95% CI: 0.47-0.84, P = 0.002) compared to chemotherapy alone. Notable increases in pCR were observed in TNBC (triple-negative breast cancer) and hormone receptor (HoR)-positive HER2-negative breast cancer (TNBC: OR = 0.56, 95% CI: 0.40-0.79, P <0.0001; HoR + HER2-: OR = 0.55, 95% CI: 0.43-0.70, P = 0.0001). In patients with metastatic lymph nodes, ICI significantly improved pCR (OR = 0.50, 95% CI: 0.39-0.63, P <0.00001). Benefits were seen with anthracycline and platinum-based chemo-backbones (carboplatin: OR = 0.65, 95% CI: 0.50-0.86, P = 0.003; non-carboplatin: OR = 0.47, 95% CI: 0.26-0.84, P = 0.01). PD-L1 status also influenced ICI benefits (PD-L1 positive: OR = 0.62, 95% CI: 0.46-0.85, P = 0.003; PD-L1 negative: OR = 0.73, 95% CI: 0.56-0.96, P = 0.03). In terms of safety, we found that the ICI combined with chemotherapy group had a significantly higher incidence of hypothyroidism and hyperthyroidism in patients with eTNBC (hypothyroidism: OR = 5.26, 95% CI: 3.21-8.60, P <0.00001; hyperthyroidism: OR = 6.26, 95% CI: 2.77-14.16, P <0.0001).
CONCLUSION
Neoadjuvant ICIs with chemotherapy improve efficacy, survival, and prognosis in early-stage breast cancer, particularly in patients with metastatic lymph nodes. Further investigation is needed for regimen and chemo-backbone duration. And the addition of ICI had a negative effect on thyroid function. Therefore, active surveillance and regular follow-up are necessary during treatment.
目的
本研究评估免疫检查点抑制剂（ICI）联合化疗对不同乳腺癌亚型的有效性和安全性，并根据淋巴结和化疗主干状态评估新辅助免疫治疗的益处。
方法
我们系统回顾了来自PubMed、EMBASE、Cochrane图书馆和肿瘤学会议的随机对照试验（RCT），这些试验涉及以PD-1/PD-L1抑制剂联合化疗作为乳腺癌新辅助治疗。终点指标为病理完全缓解（pCR）、无事件生存期（EFS）、无进展生存期（PFS）、总生存期（OS）和不良事件（AE）。使用Review Manager（5.4版）提取比值比（OR）、风险比（HR）和95%置信区间（CI）进行荟萃分析。
结果
对来自八项RCT的3739例患者的分析表明，与单纯化疗相比，ICI联合化疗显著提高了pCR（OR = 0.61，95% CI：0.48 - 0.77，P = 0.0005）、EFS（HR = 0.72，95% CI：0.59 - 0.87，P = 0.0008）和OS（HR = 0.63，95% CI：0.47 - 0.84，P = 0.002）。在三阴性乳腺癌（TNBC）和激素受体（HoR）阳性HER2阴性乳腺癌中观察到pCR显著增加（TNBC：OR = 0.56，95% CI：0.40 - 0.79，P <0.0001；HoR + HER2 -：OR = 0.55，95% CI：0.43 - 0.70，P = 0.0001）。在有转移淋巴结的患者中，ICI显著提高了pCR（OR = 0.50，95% CI：0.39 - 0.63，P <0.00001）。蒽环类和铂类化疗主干方案显示出益处（卡铂：OR = 0.65，95% CI：0.50 - 0.86，P = 0.003；非卡铂：OR =
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