Personeni Nicola, Pressiani Tiziana, Zanuso Valentina, Casadei-Gardini Andrea, D'Alessio Antonio, Valgiusti Martina, Dadduzio Vincenzo, Bergamo Francesca, Soldà Caterina, Rizzato Mario Domenico, Giordano Laura, Santoro Armando, Rimassa Lorenza
Department of Biomedical Sciences, Humanitas University, 20072 Milan, Italy.
Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, 20089 Milan, Italy.
J Pers Med. 2022 Oct 17;12(10):1726. doi: 10.3390/jpm12101726.
Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously treated with sorafenib and enrolled in second-line clinical trials were pooled according to the investigational treatment received and the subsequent regulatory approval: approved targeted agents and immune checkpoint inhibitors (AT) or other agents (OT) not subsequently approved. Univariate and multivariate analyses using Cox proportional hazards models established relationships among treatments received, clinical variables, and overall survival (OS) or PTS. For 174 patients (80 AT; 94 OT) analyzed, baseline factors for longer OS in multivariate analysis were second-line AT, absence of both portal vein thrombosis and extrahepatic spread (EHS). Treatment with AT (versus OT) was associated with significantly longer OS among patients with EHS (pinteraction = 0.005) and patients with low neutrophil-to-lymphocyte ratio (NLR; pinteraction = 0.032). Median PTS was 4.0 months (95% CI 2.8−5.3). At second-line treatment discontinuation, alpha-fetoprotein (AFP) levels <400 ng/dl, albumin-bilirubin (ALBI) grade 1, and enrolment onto subsequent trials independently predicted longer PTS. Treatment with AT, PVT, and EHS were prognostic factors for OS, while AFP, ALBI grade and enrolment onto a third-line trial were prognostic for PTS. Presence of EHS and low NLR were predictors of greater OS benefit from AT.
二线治疗是肝功能良好但对一线治疗不耐受或出现进展的晚期肝细胞癌（HCC）患者的标准治疗方案。然而，治疗获益和治疗后生存期（PTS）的决定因素仍不清楚。根据接受的研究性治疗及随后的监管批准情况，将先前接受索拉非尼治疗并参加二线临床试验的HCC患者进行分组：批准的靶向药物和免疫检查点抑制剂（AT）组或随后未获批准的其他药物（OT）组。使用Cox比例风险模型进行单变量和多变量分析，以确定接受的治疗、临床变量与总生存期（OS）或PTS之间的关系。在分析的174例患者（80例AT组；94例OT组）中，多变量分析显示OS较长的基线因素为二线AT治疗、无门静脉血栓形成和肝外转移（EHS）。在有EHS的患者（p交互作用 = 0.005）和中性粒细胞与淋巴细胞比值（NLR）较低的患者（p交互作用 = 0.032）中，AT治疗（与OT治疗相比）与显著更长的OS相关。PTS的中位数为4.0个月（95%CI 2.8 - 5.3）。在二线治疗中断时，甲胎蛋白（AFP）水平<400 ng/dl、白蛋白 - 胆红素（ALBI）1级以及参加后续试验可独立预测PTS更长。AT治疗、门静脉血栓形成（PVT）和EHS是OS的预后因素，而AFP、ALBI分级和参加三线试验是PTS的预后因素。EHS的存在和低NLR是AT治疗使OS获益更大的预测因素。
