Effectiveness and Safety of Anlotinib with or without S-1 in the Treatment of Patients with Advanced Hepatocellular Carcinoma in Chinese Population: A Prospective, Phase 2 Study

Abstract

Objective: To observe the safety and efficacy of anlotinib (ANL) alone or combined with S-1 in the first-line treatment of advanced hepatocellular carcinoma (HCC).

Methods: 54 patients with untreated advanced HCC who could not be resected were randomly divided into ANL group (n = 27) and ANL+S-1 group (n = 27). The ANL group was given ANL 10mg orally once a day for 14 consecutive days, stopped for 1 week, and repeated every 21 days. ANL+S-1 group was given ANL 10mg, once a day orally, and S-1 40mg, twice a day orally, for 14 consecutive days, stopped for 1 week, repeated every 21 days. All patients were treated until the disease progressed or toxicity become unacceptable. For patients who could not tolerate adverse reactions, the ANL dose should be reduced to 8mg per day. CT or MRI reviewed every 6 weeks to evaluate the efficacy. This study was registered at the Chinese Clinical Trial Registry (chictr.org.cn), registration number: ChiCTR1900022129.

Results: A total of 44 patients were included in the results analysis, including 22 patients in the ANL group and 22 patients in the ANL+S-1 group. In ANL group, the objective response rate (ORR) was 4.5% (1/22), disease control rate (DCR) was 77.3% (17/22), median PFS was 4.2 months (95%CI: 3.6-6.0) and median OS was 7.0 months (95%CI: 6.3-9.0), respectively. In ANL+S-1 group: the ORR was 18.2% (4/22), the DCR was 59.1% (13/22), median PFS was 4.0 months (95%CI: 3.6-5.4) and median OS was 6.0 months (95%CI: 5.5-7.4), respectively. There was no significant difference in ORR (p=0.345) and DCR (p=0.195) between the two groups. Adverse reactions were mainly hypertension, anorexia, fatigue, liver transaminase heighten and hand and foot skin reaction.

Conclusion: ANL monotherapy is effective in the treatment of advanced HCC, and adverse reactions can be tolerated.