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

Abstract

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.

Toripalimab: the First Domestic Anti-Tumor PD-1 Antibody in China

“…The effect of the combination regime was also explored in a prospective phase II trial, showing an ORR of 63.9% and median PFS of 10.5 months among 36 treatment-naive advanced HCC patients ( 87 ). Anlotinib, a novel multi-targeting tyrosine kinase inhibitor, has shown promising efficacy and safety as a first- or second-line treatment strategy in advanced HCC ( 88 ). The combination of toripalimab and anlotinib conferred an ORR of 21.4% (3/14) and a DCR of 92.9% (13/14) among treatment-naive patients with advanced HCC ( 89 , 90 ).…”

Effectiveness and Safety of Anlotinib with or without PD-1 Blockades in the Treatment of Patients with Advanced Primary Hepatocellular Carcinoma: A Retrospective, Real-World Study in China

“…Besides, our result was also higher than that reported by Sun et al, which indicated an ORR of 8.3% and 3.9%, respectively, in patients who received anlotinib with or without prior TKIs. 21 The reason for the dramatic improvement in ORR with anlotinib monotherapy over previous reports might result from a bias introduced by the small sample size in these studies. Moreover, the baseline characteristics of included patients (Child-Pugh class, BCLC stage, and CNLC stage), the initial dose of anlotinib, and previous treatment history may also contribute to the discrepancy in ORR.…”

“… 20 Based on the above results, a Phase II study was performed to assess the efficacy and safety of anlotinib as a first- or second-line treatment for patients with advanced HCC. 21 The results showed that anlotinib showed promising efficacy and safety in advanced HCC, with a 12-week progression-free survival (PFS) rate of 80.8% and 72.5%, respectively, in patients who received anlotinib with or without prior tyrosine kinase inhibitors (TKIs). 21 As the sample size of the phase II study was limited, the efficacy of anlotinib in advanced HCC still needed to be further verified by expanded clinical research.…”

“… 21 The results showed that anlotinib showed promising efficacy and safety in advanced HCC, with a 12-week progression-free survival (PFS) rate of 80.8% and 72.5%, respectively, in patients who received anlotinib with or without prior tyrosine kinase inhibitors (TKIs). 21 As the sample size of the phase II study was limited, the efficacy of anlotinib in advanced HCC still needed to be further verified by expanded clinical research. Moreover, a preclinical study has shown that anlotinib can ameliorate the tumor immune microenvironment by downregulating PD-L1 expression to inhibit tumor growth.…”

Improving Outcomes of Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma: New Data and Ongoing Trials

“…The 12-week PFS rates for cohort 1 and 2 were 80.8% and 72.5%, and the median time to progression were 5.9 months and 4.6 months, respectively. In advanced HCC, anlotinib demonstrated potential effectiveness and safety as a firstor second-line therapy when used in conjunction with a continuous TKIs treatment approach (48). In the treatment for 13 advanced HCC patients with Anlotinib plus AK105, the ORR is 23.3%, and the DCR is 69.2%.…”