Introduction: Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC. Methods: Eligible patients had confirmed aHCC, no prior systemic therapy, ≥1 measurable lesion, Eastern Cooperative Oncology Group performance status ≤1, and Child-Pugh class A disease. Patients received avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and investigator-assessed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) for HCC. Results: Twenty-two Japanese patients were enrolled and treated with avelumab plus axitinib. The minimum follow-up was 18 months as of October 25, 2019 (data cutoff). Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (72.7%); the most common (≥3 patients) were hypertension (n = 11 [50.0%]), palmar-plantar erythrodysesthesia syndrome (n = 5 [22.7%]), and decreased appetite (n = 3 [13.6%]). No grade 4 TRAEs or treatment-related deaths occurred. Ten patients (45.5%) had an immune-related AE (irAE) of any grade; 3 patients (13.6%) had an infusion-related reaction (IRR) of any grade, and no grade ≥3 irAE and IRR were observed. The objective response rate was 13.6% (95% CI: 2.9–34.9%) per RECIST 1.1 and 31.8% (95% CI: 13.9–54.9%) per mRECIST for HCC. Conclusion: Treatment with avelumab plus axitinib was associated with a manageable toxicity profile and showed antitumor activity in patients with aHCC.
Liver Cancer

中文翻译：

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Avelumab与Axitinib联合作为晚期肝细胞癌患者的一线治疗：1b期VEGF肝100期试验的结果

简介：将免疫检查点抑制剂与靶向抗血管生成剂联合使用可能会利用互补的作用机制来治疗晚期/转移性肝细胞癌（aHCC）。Avelumab是一种人类抗PD-L1 IgG1抗体，在多种肿瘤类型中均具有临床活性；axitinib是血管内皮生长因子受体1、2和3的选择性酪氨酸激酶抑制剂。我们报告了VEGF Liver 100（NCT03289533）的最终分析结果，这是一项1b期研究，评估avelumab和axitinib在未接受过治疗的患者中的安全性和有效性与aHCC。方法：符合条件的患者已确诊为aHCC，未曾进行过全身治疗，病灶≥1个，东部合作肿瘤小组的工作状态≤1，Child-Pugh A级疾病。患者每2周静脉注射avelumab 10 mg / kg加阿西替尼5 mg每天口服两次，直至病情恶化，毒性不可接受或停药。终点包括安全性和根据实物肿瘤反应评估标准（RECIST）1.1和针对HCC的改良RECIST（mRECIST）进行的研究者评估的客观反应。结果：22名日本患者入选并接受avelumab加阿昔替尼治疗。截至2019年10月25日，最低随访时间为18个月（数据截止）。16例患者（72.7％）发生了3级治疗相关不良事件（TRAE）；最常见（≥3例）为高血压（n= 11 [50.0％]），掌-红斑感觉异常综合征（n = 5 [22.7％]）和食欲下降（n = 3 [13.6％]）。没有发生4级TRAE或与治疗相关的死亡。十名患者（45.5％）患有任何级别的免疫相关性AE（irAE）；3名患者（13.6％）出现任何级别的输注相关反应（IRR），并且未观察到≥3级的irAE和IRR。每个RECIST 1.1的客观应答率为13.6％（95％CI：2.9-34.9％），对于肝癌，每个mRECIST的客观缓解率为31.8％（95％CI：13.9-54.9％）。结论： avelumab加阿昔替尼治疗与可控制的毒性有关，并显示出对aHCC患者的抗肿瘤活性。
肝癌