Department of Minimal Invasive Intervention, Sun Yat-sen University Cancer Center, Guangzhou, China.
State Key Laboratory of Oncology in South China, Guangzhou, China.
Cancer. 2023 Jul 15;129(14):2235-2244. doi: 10.1002/cncr.34764. Epub 2023 Apr 7.
This study compares the efficacy and safety of lenvatinib and programmed cell death protein (PD)-1 versus lenvatinib alone for advanced hepatocellular carcinoma (Ad-HCC) refractory to hepatic arterial infusion chemotherapy (HAIC).
From April 2016 to September 2021, 145 patients with Ad-HCC refractory to HAIC based on modified Response Evaluation Criteria in Solid Tumors criteria were enrolled by two radiologists and classified into the HAIC-lenvatinib group (H-L, n = 87) and HAIC-lenvatinib-PD-1 group (H-L-P, n = 58). A propensity score-matching method was used to reduce selective bias. The overall survival (OS) and postprogression-free survival (PPS) rates were compared using the Kaplan-Meier method with log-rank test. Multivariable analyses of independent prognostic factors were evaluated by means of the forward stepwise Cox regression model.
After propensity score matching 1:1, the median OS was 43.6 months in the H-L-P group and was significantly longer than that (18.9 months) of the H-L group (p = .009). The median PPS was 35.6 months in the H-L-P group and was significantly longer than that (9.4 months) of the H-L group (p = .009). Multivariate analyses showed that the factors that significantly affected the OS were α-fetoprotein (hazard ratio [HR], 2.14; 95% CI, 1.26-3.98; p = .006), early response to HAIC (HR, 0.44; 95% CI, 1.20-3.85; p = .009), and H-L treatment (HR, 0.52; 95% CI, 0.30-0.86; p = .012). Modified albumin-bilirubin grade (HR, 1.32; 95% CI, 1.03-1.70; p = .026), early response to HAIC (HR, 0.44; 95% CI, 0.25-0.77; p = .004), and H-L (HR, 0.47; 95% CI, 0.28-0.78; p = .003) significantly affected the PPS.
This combination therapy of PD-1 inhibitors plus lenvatinib has promising survival benefits in the management of patients with Ad-HCC refractory to HAIC.
Lenvatinib plus programmed death 1 inhibitor is an effective and safe postprogression treatment and improved significantly overall survival and postprogression-free survival compared with lenvatinib alone in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.
本研究比较了仑伐替尼联合程序性死亡蛋白（PD）-1 与仑伐替尼单药治疗对经肝动脉灌注化疗（HAIC）耐药的晚期肝细胞癌（Ad-HCC）的疗效和安全性。
本研究纳入了 2016 年 4 月至 2021 年 9 月期间，根据实体瘤反应评价标准改良版（mRECIST），145 名对 HAIC 耐药的 Ad-HCC 患者，由两名放射科医生将患者分为 HAIC-仑伐替尼组（H-L，n=87）和 HAIC-仑伐替尼-PD-1 组（H-L-P，n=58）。采用倾向评分匹配法减少选择性偏倚。采用 Kaplan-Meier 法和对数秩检验比较总生存期（OS）和进展后无进展生存期（PPS）。采用向前逐步 Cox 回归模型对独立预后因素进行多变量分析。
经过 1:1 倾向评分匹配后，H-L-P 组的中位 OS 为 43.6 个月，明显长于 H-L 组的 18.9 个月（p=0.009）。H-L-P 组的中位 PPS 为 35.6 个月，明显长于 H-L 组的 9.4 个月（p=0.009）。多变量分析显示，影响 OS 的因素有α-胎蛋白（HR，2.14；95%CI，1.26-3.98；p=0.006）、HAIC 早期反应（HR，0.44；95%CI，1.20-3.85；p=0.009）和 H-L 治疗（HR，0.52；95%CI，0.30-0.86；p=0.012）。改良的白蛋白-胆红素分级（HR，1.32；95%CI，1.03-1.70；p=0.026）、HAIC 早期反应（HR，0.44；95%CI，0.25-0.77；p=0.004）和 H-L（HR，0.47；95%CI，0.28-0.78；p=0.003）显著影响 PPS。
PD-1 抑制剂联合仑伐替尼治疗对 HAIC 耐药的 Ad-HCC 患者具有良好的生存获益。
