Biomarkers for predicting tumor response to PD-1 inhibitors in patients with advanced pancreatic cancer

Pancreatic cancer is among the most lethal malignant neoplasms, and few patients with pancreatic cancer benefit from immunotherapy. We retrospectively analyzed advanced pancreatic cancer patients who received PD-1 inhibitor-based combination therapies during 2019–2021 in our institution. The clinical characteristics and peripheral blood inflammatory markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], and lactate dehydrogenase [LDH]) were collected at baseline. Chi-squared and Fisher’s exact tests were used to evaluate relationships between the above parameters and tumor response. Cox regression analyses were employed to assess the effects of baseline factors on patients’ survival and immune-related adverse events (irAEs). Overall, 67 patients who received at least two cycles of PD-1 inhibitor were considered evaluable. A lower NLR was independent predictor for objective response rate (38.1% vs. 15.2%, <i>P</i> = .037) and disease control rate (81.0% vs. 52.2%, <i>P</i> = .032). In our study population, patients with lower LDH had superior progression-free survival (PFS) and overall survival(OS) (mPFS, 5.4 vs. 2.8 months, <i>P</i> &lt; .001; mOS, 13.3 vs. 3.6 months, <i>P</i> &lt; .001). Liver metastasis was verified to be a negative prognostic factor for PFS (2.4 vs. 7.8 months, <i>P </i>&lt; .001) and OS (5.7 vs. 18.0 months, <i>P</i> &lt; .001). The most common irAEs were hypothyroidism (13.4%) and rash (10.5%). Our study demonstrated that the pretreatment inflammatory markers were independent predictors for tumor response, and the baseline LDH level and liver metastasis were potential prognostic markers of survival in patients with pancreatic cancer treated with PD-1 inhibitors.

胰腺癌是致死性最高的恶性肿瘤之一，仅有少数胰腺癌患者可从免疫治疗中获益。本研究回顾性分析了2019年至2021年期间本机构内接受以PD-1抑制剂为基础的联合治疗的晚期胰腺癌患者。收集了患者基线状态下的临床特征与外周血炎症标志物，包括中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、淋巴细胞与单核细胞比值（LMR）以及乳酸脱氢酶（LDH）。采用卡方检验与Fisher确切概率法评估上述指标与肿瘤应答的相关性；采用Cox回归分析探究基线因素对患者生存结局与免疫相关不良事件（irAEs）的影响。最终纳入67例至少接受2个周期PD-1抑制剂治疗的可评估患者。较低的NLR是客观缓解率（38.1% vs 15.2%，P=0.037）与疾病控制率（81.0% vs 52.2%，P=0.032）的独立预测因子。在本研究队列中，基线LDH水平较低的患者无进展生存期（PFS）与总生存期（OS）更优：中位PFS为5.4 vs 2.8个月（P<0.001），中位OS为13.3 vs 3.6个月（P<0.001）。肝转移被证实为影响患者PFS（2.4 vs 7.8个月，P<0.001）与OS（5.7 vs 18.0个月，P<0.001）的不良预后因素。本研究中最常见的免疫相关不良事件为甲状腺功能减退症（13.4%）与皮疹（10.5%）。本研究证实，治疗前外周血炎症标志物可作为肿瘤应答的独立预测因子，基线LDH水平与肝转移则是接受PD-1抑制剂治疗的胰腺癌患者生存结局的潜在预后标志物。