Sorafenib as second‐line treatment option after failure of lenvatinib in patients with unresectable hepatocellular carcinoma

Abstract

Background and Aim Currently, there is no molecular‐targeted agent that has demonstrated evidence of efficacy in patients with unresectable hepatocellular carcinoma (u‐HCC) who have developed resistance to treatment with lenvatinib (LEN). In this real‐world study, we aimed to investigate the therapeutic effect and safety of sorafenib (SOR) in patients with u‐HCC after progression on treatment with LEN. Methods (Patients) and Results A total of 13 patients with u‐HCC (12 males and 1 female), who were treated with SOR after progression on LEN, were enrolled in this retrospective study. Therapeutic efficacy was evaluated via contrast‐enhanced computerized tomography at 8 weeks after the initiation of SOR therapy according to modified response evaluation criteria in solid tumors (mRECIST) and RECIST. According to mRECIST, the objective response rate (ORR) and disease control rate (DCR) were 15.3% (2/13) and 69.2% (9/13), respectively. According to RECIST, the ORR and DCR were 0% (0/13) and 69.2% (9/13), respectively. The median progression‐free survival was 4.1 months. The median albumin‐bilirubin scores did not deteriorate significantly at 4, 6, and 8 weeks after initiation of SOR, compared with the scores at the baseline. The most frequent grade 1 or 2 adverse events (AEs) were palmar–plantar erythrodysesthesia, fatigue, diarrhea, and hypertension. There was no incidence of grade 3 AEs. Conclusion Treatment with SOR may be effective for u‐HCC after failure on LEN and may not worsen the liver reserve.

Comparison of therapeutic outcomes of sorafenib and lenvatinib as primary treatments for hepatocellular carcinoma with a focus on molecular‐targeted agent sequential therapy: A propensity score‐matched analysis

“…8,9 In contrast, the therapeutic efficacy and safety of SOR or RAM after disease progression following LEN treatment has been reported in small cohort studies. 10,11 These findings indicate the feasibility of sequential MTA therapies for the treatment of u-HCC. However, the REFLECT study was conducted before second-line MTA therapy became fully available in practice; the patients in that study were recruited before 2015, and November 13, 2016 was set as the data cut-off date.…”

“…Moreover, the effectiveness of treatment with LEN after progression following SOR treatment has been reported in retrospective studies 8,9 . In contrast, the therapeutic efficacy and safety of SOR or RAM after disease progression following LEN treatment has been reported in small cohort studies 10,11 . These findings indicate the feasibility of sequential MTA therapies for the treatment of u‐HCC.…”

Comparative study between sorafenib and lenvatinib as the first‐line therapy in the sequential treatment of unresectable hepatocellular carcinoma in a real‐world setting

“…The evidence for second-line treatment after sorafenib is well established, and three agents-regorafenib, ramucirumab, and cabozantinib-have shown clinical benefits in phase 3 trials. [7][8][9] In contrast, unlike sorafenib, second-line treatment after lenvatinib has not been firmly established-several studies have been reported [28][29][30] but were based on a small number of patients, leaving insufficient evidence. In addition, there were a few options for subsequent treatment in the lenvatinib group because cabozantinib was not a treatment option during the study period.…”

Comparison of the outcomes between sorafenib and lenvatinib as the first-line systemic treatment for HBV-associated hepatocellular carcinoma: a propensity score matching analysis

“…Another reason why the sorafenib group had more patients to receive subsequent treatment might be related to the insurance system for second-line treatment. Unlike sorafenib, there is no evidence for the effectiveness of molecularly targeted agents in advanced HCC after progression following lenvatinib treatment [ 29 ]. However, sequential treatment with sorafenib-regorafenib is covered by the National Health Insurance System of Korea after RESORCE trial, and in a previous study, 26-month survival was reportedly possible [ 30 ].…”