Predictors of Response and Survival in Immune Checkpoint Inhibitor-Treated Unresectable Hepatocellular Carcinoma
Predictors of Response and Survival in Immune Checkpoint Inhibitor-Treated Unresectable Hepatocellular Carcinoma
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DOI：
10.3390/cancers12010182
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发表时间：
2020-01-01
期刊：
影响因子：
5.2
通讯作者：
Huang, Yi-Hsiang
中科院分区：
文献类型：
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作者：
Lee, Pei-Chang;Chao, Yee;Huang, Yi-Hsiang
nivolumab和pembrolizumab的免疫检查点抑制剂（ICI）是治疗晚期肝细胞癌（HCC）的有前途的药物，但缺乏有效的生物标志物。我们的目的是研究在不能切除的HCC患者中ICI治疗的反应的潜在预测因子和与总生存期（OS）相关的因素。95例接受nivolumab或pembrolizumab治疗不可切除HCC的患者入组分析。影像学评价基于RECIST v1.1。分析与结局相关的因素。在90例图像可评价的患者中，客观缓解率（ORR）为24.4%。Child-Pugh A级或接受联合治疗的患者的ORR较高。早期甲胎蛋白（AFP）降低>10%（4周内）是最佳客观缓解的唯一独立预测因素（比值比：7.259，p = 0.001）。对于基线AFP >= 10 ng/mL的患者，观察到早期AFP降低的患者的ORR（63.6% vs. 10.2%，p < 0.001）和疾病控制率（81.8% vs. 14.3%，p < 0.001）显著高于未降低的患者。此外，在不同模型中，早期AFP降低和白蛋白胆红素（ALBI）分级或Child-Pugh分级是与OS相关的独立因素。总之，早期AFP应答的10-10规则可以预测不能切除的HCC对ICI治疗的客观应答和生存率。ALBI分级和Child-Pugh分级决定ICI治疗的生存率。
Immune checkpoint inhibitors (ICIs) with nivolumab and pembrolizumab are promising agents for advanced hepatocellular carcinoma (HCC) but lack of effective biomarkers. We aimed to investigate the potential predictors of response and factors associated with overall survival (OS) for ICI treatment in unresectable HCC patients. Ninety-five patients who received nivolumab or pembrolizumab for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on RECIST v1.1. Factors associated with outcomes were analyzed. Of 90 patients with evaluable images, the objective response rate (ORR) was 24.4%. Patients at Child-Pugh A or received combination treatment had higher ORR. Early alpha-fetoprotein (AFP) >10% reduction (within 4 weeks) was the only independent predictor of best objective response (odds ratio: 7.259, p = 0.001). For patients with baseline AFP >= 10 ng/mL, significantly higher ORR (63.6% vs. 10.2%, p < 0.001) and disease control rate (81.8% vs. 14.3%, p < 0.001) were observed in those with early AFP reduction than those without. In addition, early AFP reduction and albumin-bilirubin (ALBI) grade or Child-Pugh class were independent factors associated with OS in different models. In conclusion, a 10-10 rule of early AFP response can predict objective response and survival to ICI treatment in unresectable HCC. ALBI grade and Child-Pugh class determines survival by ICI treatment.