扩展 PD-L1 范式：系统综述和荟萃分析影响乳腺癌免疫检查点抑制剂疗效的评分系统和其他生物标志物。
Expanding the PD-L1 Paradigm: A Comprehensive Systematic Review and Meta-Analysis of Scoring Systems and Additional Biomarkers Influencing Immune Checkpoint Inhibitor Outcomes in Breast Cancer.
机构信息
Department of Breast, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, P.R. China.
School of Medicine, South China University of Technology, Guangzhou, P.R. China.
出版信息
Cancer Control. 2024 Jan-Dec;31:10732748241299074. doi: 10.1177/10732748241299074.
OBJECTIVES
The study aimed to conduct an in-depth analysis of the influence of PD-L1 status and expression levels and other variables on the effectiveness of immune checkpoint inhibitors (ICIs) in treating breast cancer.
METHODS
A total of 19 articles, involving 16 trials and 7899 patients, were included in the analysis. The outcomes of interest were odds-ratio (OR) for pathological complete response (pCR) in early breast cancer, and hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) in advanced breast cancer.
RESULTS
In early breast cancer, individuals with PD-L1-positive tumors were more likely to benefit from ICIs than those with PD-L1-negative tumors. Furthermore, patients with PD-L1 positivity in immune cells (IC) had superior outcomes compared to those scoring positively on combined positive score (CPS), with ORs for ICIs benefit being 2.28 for IC-positive patients vs 1.78 for CPS-positive patients. Regarding the impact of breast cancer subtypes on the efficacy of ICIs, our findings indicated that triple-negative breast cancer (TNBC) exhibits the greatest therapeutic response with OR of 1.93, followed by the hormone receptor-positive (HoR+) / human epidermal growth factor receptor 2-negative (HER2-), while the HER2+ was the worst. Additionally, age was identified as a key predictive factor in responding to ICIs. In advanced breast cancer, there was an upward trend in CPS values associated with enhanced ICIs responsiveness, with the predictive value increasing from 12% at a CPS threshold of 10 to 13.6% at 20.
CONCLUSION
The study concluded that the PD-L1 expression scoring system effectively discriminates between patients with breast cancer in terms of the degree of benefit they may attain from ICIs. Patients with little or no PD-L1 expression experienced a diminished therapeutic benefit from ICIs.
目的
本研究旨在深入分析 PD-L1 状态和表达水平等变量对免疫检查点抑制剂（ICI）治疗乳腺癌疗效的影响。
方法
共纳入 19 项研究，包括 16 项试验和 7899 例患者。主要结局为早期乳腺癌的病理完全缓解（pCR）的比值比（OR），晚期乳腺癌的无进展生存期（PFS）和总生存期（OS）的风险比（HR）。
结果
在早期乳腺癌中，PD-L1 阳性肿瘤患者比 PD-L1 阴性肿瘤患者更有可能从 ICI 中获益。此外，与 CPS 阳性患者相比，免疫细胞（IC）中 PD-L1 阳性患者的结局更好，IC 阳性患者的 ICI 获益 OR 为 2.28，而 CPS 阳性患者的 OR 为 1.78。关于乳腺癌亚型对 ICI 疗效的影响，我们的研究结果表明，三阴性乳腺癌（TNBC）的治疗反应最大，OR 为 1.93，其次是激素受体阳性（HoR+）/人表皮生长因子受体 2 阴性（HER2-），而 HER2+则最差。此外，年龄是对 ICI 反应的关键预测因素。在晚期乳腺癌中，CPS 值与 ICI 反应性的增强呈正相关趋势，CPS 阈值为 10 时的预测值为 12%，20 时为 13.6%。
结论
该研究表明，PD-L1 表达评分系统能够有效区分乳腺癌患者从 ICI 中获益的程度。PD-L1 低表达或无表达的患者从 ICI 中获益减少。
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