Önder Tuğba, Öner İrem, Karaçin Cengiz, Ateş Öztürk
Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Health Sciences University, Ankara, Turkey.
Int J Clin Oncol. 2025 Apr 21. doi: 10.1007/s10147-025-02770-w.
Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy, the standard of care for metastatic hormone receptor-positive (HR +)/human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC), has profoundly affected many cell types, including tumor cells, Tregs, cytotoxic T cells, and stem and progenitor cells. Therefore, it is reasonable to assume that the pretreatment status of tumor immunity may have predictive value in CDK4/6i efficacy.
A total of 404 patients were included in the analysis. The scores of the panimmune-inflammatory values (PIV) and PILE (PIV-LDH-ECOG), a candidate PIV-based scoring system, were calculated within one week before the initiation of CDK4/6i plus endocrine therapy (ET).
The median overall survival (OS) was 69.0 months (95% CI 51.1-86.8). The low-PIV subgroup had significantly longer progression-free survival (PFS) [23.9 vs. 18.8 months; HR = 1.817, 95% CI = 1.113-2.965, p = 0.017] and OS [73.6 vs. 37.7 months; HR = 2.338, 95% CI = 1.122-4.871, p = 0.023] than the high-PIV subgroup. In the low-risk PILE subgroup, PFS [37.0 vs. 15.8 months; HR = 2.751, 95% CI = 1.736-4.361, p < 0.001] and OS [73.6 vs. 35.1 months; HR = 3.854, 95% CI = 1.855-8.005, p < 0.001] were greater than in the high-risk PILE subgroup. The low-risk PILE subgroup was associated with a significantly better disease control rate (DCR) than the high-risk PILE subgroup (87.2% and 75.0%, p = 0.004). In the analysis of 112 patients treated with ET in the metastatic stage before CDK4/6i as a control group, PIV and PILE were not independent prognostic indicators.
Our study demonstrated that PIV and PILE scores could be predictive biomarkers for the treatment efficacy of CDK4/6is.
细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）疗法是转移性激素受体阳性（HR+）/人表皮生长因子受体2（HER2）阴性乳腺癌（BC）的标准治疗方案，已对包括肿瘤细胞、调节性T细胞、细胞毒性T细胞以及干细胞和祖细胞在内的多种细胞类型产生了深远影响。因此，有理由推测肿瘤免疫的预处理状态可能对CDK4/6i疗效具有预测价值。
共纳入404例患者进行分析。在开始CDK4/6i加内分泌治疗（ET）前一周内计算全免疫炎症值（PIV）和基于PIV的候选评分系统PILE（PIV-LDH-ECOG）的分数。
中位总生存期（OS）为69.0个月（95%CI 51.1 - 86.8）。低PIV亚组的无进展生存期（PFS）[23.9 vs. 18.8个月；HR = 1.817，95%CI = 1.113 - 2.965，p = 0.017]和OS[73.6 vs. 37.7个月；HR = 2.338，95%CI = 1.122 - 4.871，p = 0.023]均显著长于高PIV亚组。在低风险PILE亚组中，PFS[37.0 vs. 15.8个月；HR = 2.751，95%CI = 1.736 - 4.361，p < 0.001]和OS[73.6 vs. 35.1个月；HR = 3.854，95%CI = 1.855 - 8.005，p < 0.001]均高于高风险PILE亚组。低风险PILE亚组的疾病控制率（DCR）显著高于高风险PILE亚组（87.2%和75.0%，p = 0.004）。在以112例在CDK4/6i之前处于转移阶段接受ET治疗的患者作为对照组的分析中，PIV和PILE不是独立的预后指标。
我们的研究表明，PIV和PILE分数可能是CDK4/6i治疗疗效的预测生物标志物。
