Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1)
Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1)
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奥沙利铂加氟尿嘧啶与索拉非尼治疗晚期肝细胞癌的动脉化疗：生物分子探索性、随机、III 期试验 (FOHAIC-1)
DOI：
10.1200/jco.21.01963
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发表时间：
2022-02-10
影响因子：
45.3
通讯作者：
Zhao, Ming
中科院分区：
文献类型：
--
作者：
Lyu, Ning;Wang, Xun;Zhao, Ming
目的。氟尿嘧啶、亚叶酸钙和奥沙利铂的介入肝动脉化疗(HAIC-FO)在先前的II期试验和一项涉及局部晚期肝细胞癌(HCC)患者的倾向评分匹配研究中显示出令人鼓舞的安全性和抗肿瘤活性。方法在这项开放的III期试验中，未接受系统治疗的晚期肝癌患者按1：1的比例随机分配接受HAIC-FO或索拉非尼治疗。主要终点是意向治疗人群的总体存活率(OS)。结果2017年5月至2020年5月，262例HAIC-FO患者被随机分配。肿瘤大小中位数为11.2 cm(四分位数范围8.5~13.7 cm)。大血管受累占65.6%，肿瘤体积50%受累于肝脏和/或门静脉癌栓的患者占49.2%。在数据截止时(2020年10月31日)，HAIC-FO组和索拉非尼组的中位OS分别为13.9个月和8.2月(危险比[HR]0.408；95%CI，0.301至0.552；P<；.001)。接受HAIC-FO治疗的患者中有16例(12.3%)发生了肿瘤降期，其中15例接受了根治性手术或消融，最终获得中位OS为20.8个月，1年OS率为93.8%。在高危人群中，HAIC-FO组的OS显著长于索拉非尼组(10.8个月对5.7月；HR 0.343；95%CI，0.219至0.538；P<；.001)。一个新开发的15个突变基因预测模型确定了83%的对HAIC-FO有反应的患者。HAIC-FO应答者的OS较HAIC-FO无应答者长(19.3个月vs10.6个月；HR 0.323；95%CI，0.186~0.560；P=0.002)。结论HAIC-FO治疗晚期肝癌，即使伴有较高的肝内疾病负担，也比索拉非尼有更好的生存结局。(C)2021年，美国临床肿瘤学会
PURPOSE. Interventional hepatic arterial infusion chemotherapy of infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) displayed an encouraging safety profile and antitumor activity in a previous phase II trial and a propensity-score-matching study involving patients with locally advanced hepatocellular carcinoma (HCC).METHODS In this open-label, phase III trial, patients with advanced HCC, previously untreated with systemic therapy, were randomly assigned in a 1:1 ratio to receive HAIC-FO or sorafenib. The primary end point was overall survival (OS) in the intention-to-treat population. An exploratory model for predicting the efficacy of HAIC-FO on the basis of genomic sequencing was developed.RESULTS Between May 2017 and May 2020, 262 patients were randomly assigned. The median tumor size was 11.2 cm (interquartile range, 8.5-13.7 cm). Macrovascular invasion was present in 65.6%, and the percentage of patients with > 50% tumor volume involvement of the liver and/or Vp-4 portal vein tumor thrombosis was 49.2%. At data cutoff (October 31, 2020), median OS was 13.9 months for HAIC-FO and 8.2 for sorafenib (hazard ratio [HR] 0.408; 95% CI, 0.301 to 0.552; P < .001). Tumor downstaging occurred in 16 (12.3% of 130) patients receiving HAIC-FO, including 15 receiving curative surgery or ablation, and finally achieving a median OS of 20.8 months, with a 1-year OS rate of 93.8%. In high-risk subpopulations, OS was significantly longer with HAIC-FO than with sorafenib (10.8 months v 5.7 months; HR 0.343; 95% CI, 0.219 to 0.538; P < .001). A newly developed 15-mutant-gene prediction model identified 83% of patients with response to HAIC-FO. HAIC-FO responders had longer OS than HAIC-FO nonresponders (19.3 months v 10.6 months; HR 0.323; 95% CI, 0.186 to 0.560; P = .002).CONCLUSION HAIC-FO achieved better survival outcomes than sorafenib in advanced HCC, even in association with a high intrahepatic disease burden. (C) 2021 by American Society of Clinical Oncology