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

Abstract

Aims: There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real-world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular-targeted therapy era. Methods and Results: We enrolled 386 patients treated with sorafenib or lenvatinib as the first-line therapy for unresectable hepatocellular carcinoma at multiple centers. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics between the two groups. Propensity score matching identified 110 patients in each treatment group. The median overall survival was similar between lenvatinib and sorafenib (14.8 and 13.0 months, respectively; P = 0.352). The median progression-free survival was longer with lenvatinib than with sorafenib (7.6 and 3.9 months, respectively; P < 0.001). The overall response rate (P < 0.001) and disease control rate (P = 0.015), as defined by the modified Response Evaluation Criteria in Solid Tumors, were significantly better with lenvatinib than with sorafenib. The median overall survival was longer in patients who received subsequent treatment than in those who did not in the sorafenib group (23.1 and 5.7 months, respectively; P < 0.001), whereas the median overall survival with or without subsequent treatment did not differ significantly in the lenvatinib group (17.8 and 14.7 months, respectively; P = 0.439). Conclusion: Overall survival with sorafenib and lenvatinib was not significantly different. However, patients who received subsequent treatments had longer overall survival than those who received only first-line treatment with sorafenib, whereas lenvatinib did not show this effect.

Efficacy and safety of lenvatinib versus sorafenib in first-line treatment of advanced hepatocellular carcinoma: A meta-analysis

“…The published year ranged from 2018 to 2022, and the regions studied included Asia, Europe, and North America. The dosage of the drugs was consistent in the majority of the studies ( 13 , 18 , 19 , 21 – 24 , 26 – 28 , 31 ). For instance, the initial dose of sorafenib was 400 mg twice daily, while lenvatinib was administered at a dose of 12 mg once daily for patients with body weights ≥ 60 kg or 8 mg once daily for those with body weights < 60 kg.…”

“…Furthermore, the cost-utility analysis showed that lenvatinib offered similar clinical effectiveness at a lower cost than sorafenib, indicating that lenvatinib may be a cost-saving alternative in patients with advanced HCC (40). However, recent studies that compared the efficacy of lenvatinib and sorafenib in HCC found conflicting results (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)41), and hence the optimal choice for the patient between these two drugs remains controversial. Therefore, our primary aim to perform this systematic review is to evaluate the feasibility and safety of lenvatinib as a first-line treatment for advanced HCC.…”

“…After a detailed reading and full text assessment, 13 articles were further excluded as they did not meet the inclusion criteria as 3 of them were reviews, 4 were not case-control studies, 2 lacked the related data, and 4 were sub-studies of previous trials. Finally, 15 articles were included in this analysis, including 1 RCT (13) and 14 retrospective cohort studies (RCS) (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). The literature selection process is shown in Figure 1.…”

“…The bias risk of one RCT (13) was assessed using the Cochrane Collaboration tool and determined to be low (Figure 2). Besides, the 14 retrospective studies (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) had NOS scores ranging from 7 to 9, indicating a high quality of data in all included studies (Table 1).…”

“…Thirteen studies (13,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)31) enrolling 3760 patients provided data concerning PFS. The pooled analysis showed that compared with sorafenib, lenvatinib was associated with significantly improved PFS (HR = 0.63; 95% CI: 0.53-0.74; p < 0.00001).…”