Anlotinib in the treatment of advanced hepatocellular carcinoma: an open-label phase II study (ALTER-0802 study)

PURPOSE: This study aimed to assess efficacy and safety of anlotinib as a first- or second-line treatment for advanced or metastatic hepatocellular carcinoma (aHCC) and to identify the predictive plasma cytokines on efficacy of anlotinib. METHODS: It was a phase II clinical study. Patients with aHCC were recruited from October 2016 to April 2019 and divided into two cohorts according to previous tyrosine kinase inhibitors (TKIs) therapy. Those without or with prior TKIs were in Cohort 1 or 2, respectively. All patients took anlotinib (12 mg/day, Day1-14, 3 weeks per cycle). The primary endpoint was 12-week progression-free survival (PFS) rate. Relationship between the series plasma cytokine level and the efficacy of anlotinib was analyzed. RESULTS: Enrolled 26 patients in Cohort 1 and 24 in Cohort 2. In Cohort 1, the 12-week PFS rate was 80.8% 95% confidence interval (CI); 59.8%-91.5% and median time to progression (TTP) was 5.9 months (95% CI 4.8-6.9). In Cohort 2, the 12-week PFS rate and median TTP was 72.5% (95% CI 48.7%-86.6%) and 4.6 months (95% CI 2.7-10.0), respectively. The median TTP on patients with a baseline plasma level of CXCL1 (C-X-C motif chemokine ligand 1) less than 7.6 ng/μl was significantly longer in both cohorts. The most common grade 3-5 adverse events were hypertension (8%), diarrhea (8%) and hand-foot syndrome (6%). CONCLUSION: Anlotinib showed promising efficacy and safety as a first- or second-line treatment with a continuous TKIs treatment strategy in aHCC. The plasma CXCL1 might be a predictor for the efficacy of anlotinib.