Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy.
Department of Oncology, Istituto Oncologico Veneto, IRCCS, Via Gattamelata, 64, 35128, Padua, Italy.
Eur J Cancer. 2021 Jun;150:155-167. doi: 10.1016/j.ejca.2021.03.043. Epub 2021 Apr 24.
Immune checkpoint inhibitors (ICIs) yielded unprecedented efficacy in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC). Since the Pan-Immune-Inflammation Value (PIV) is a blood-based biomarker with prognostic usefulness in mCRC, it might predict clinical outcomes and primary resistance to ICIs.
We retrospectively analysed the association of PIV and its early modulation at 3/4 weeks after treatment initiation with the outcomes of MSI-high mCRC patients receiving anti-programmed death-(ligand)1 (PD-[L]1) +/- anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. PIV cut-offs were determined using the maximally selected rank statistics.
A total of 163 patients were included. In the multivariable models for overall survival (OS) and progression-free survival (PFS), both high (>492) baseline PIV (OS: adjusted [a] HR, 3.00; 95% CI, 1.49-6.04, p = 0.002; PFS: aHR, 1.91; 95% CI, 1.06-3.44, p = 0.031) and early PIV increase ≥+30% (OS: aHR, 3.21; 95% CI, 1.65-6.23, p < 0.001; PFS: aHR, 2.25; 95% CI, 1.30-3.89, p = 0.003) confirmed an independent prognostic impact. After stratifying patients according to baseline PIV and ICI regimen, OS and PFS were significantly worse in subjects with high PIV receiving anti-PD-1/PD-L1 monotherapy. Early PIV increase was an independent predictor of clinical benefit (aOR, 0.23; 95% CI, 0.08-0.66; p = 0.007), whereas a trend was observed for baseline PIV (aOR, 0.33; 95% CI, 0.10-1.07; p = 0.065).
PIV is a strong predictor of outcomes in MSI-high mCRC patients receiving ICIs. Prospective validation of these results is required to establish its role as a stratification factor for personalised combination strategies.
免疫检查点抑制剂（ICIs）在微卫星不稳定（MSI）高转移性结直肠癌（mCRC）患者中产生了前所未有的疗效。由于 Pan-Immune-Inflammation Value（PIV）是一种具有 mCRC 预后作用的基于血液的生物标志物，它可能预测临床结局和对 ICI 的原发性耐药性。
我们回顾性分析了 PIV 及其在治疗开始后 3/4 周时的早期调节与接受抗程序性死亡-（配体）1（PD-（L）1）+/ -抗细胞毒性 T 淋巴细胞抗原 4（CTLA-4）药物治疗的 MSI 高 mCRC 患者结局之间的相关性。PIV 计算如下：（中性粒细胞计数×血小板计数×单核细胞计数）/淋巴细胞计数。使用最大选择秩统计确定 PIV 截断值。
共纳入 163 例患者。在总生存期（OS）和无进展生存期（PFS）的多变量模型中，基线 PIV 较高（>492）（OS：调整后的[ a] HR，3.00；95%CI，1.49-6.04，p=0.002；PFS：aHR，1.91；95%CI，1.06-3.44，p=0.031）和早期 PIV 增加≥+30%（OS：aHR，3.21；95%CI，1.65-6.23，p<0.001；PFS：aHR，2.25；95%CI，1.30-3.89，p=0.003）证实了独立的预后影响。根据基线 PIV 和 ICI 方案对患者进行分层后，高 PIV 接受抗 PD-1/PD-L1 单药治疗的患者 OS 和 PFS 明显更差。早期 PIV 增加是临床获益的独立预测因子（aOR，0.23；95%CI，0.08-0.66；p=0.007），而基线 PIV 则呈趋势（aOR，0.33；95%CI，0.10-1.07；p=0.065）。
PIV 是 MSI 高 mCRC 患者接受 ICI 治疗结局的有力预测因子。需要前瞻性验证这些结果，以确立其作为个性化联合策略分层因素的作用。
