Therapeutic efficacy of lenvatinib as third‐line treatment after regorafenib for unresectable hepatocellular carcinoma progression

Abstract

Aim Multiple molecular agents have been developed for treating unresectable hepatocellular carcinoma. This study aimed to elucidate the clinical efficacy of sequential treatment with lenvatinib after regorafenib failure. Methods From June 2017 to October 2020, 63 patients with Child–Pugh A and treated with regorafenib followed by sorafenib were enrolled (median age 71 years, 52 men, Barcelona Clinic Liver Cancer B:C = 23:40). They were divided into two groups, those treated with lenvatinib after regorafenib treatment (R‐L group, n = 47) and those who did not receive lenvatinib after regorafenib (non‐R‐L group, n = 16). Prognostic factors were retrospectively analyzed after adjustment with inverse probability weighting. Results Serum albumin level at the start of regorafenib and reasons for discontinuation of regorafenib were significantly different between the R‐L and non‐R‐L groups, whereas the albumin‐bilirubin score, Child–Pugh class, and tumor burden were not. Progression‐free survival was also not significantly different (median 4.1 vs. 3.8 months, p = 0.586). As for overall survival, the R‐L group showed better prognosis after introducing regorafenib and after introducing sorafenib, following inverse probability weighting adjustment (MST 19.7 vs. 10.3 months, 33.8 vs. 15.3 months, p < 0.001 and p = 0.022, respectively). Modified albumin‐bilirubin grade 2b (score >−2.27) at the start of regorafenib (HR 2.074, p = 0.041) and the presence of lenvatinib treatment after regorafenib failure (HR 0.355, p = 0.004) were found to be significant prognostic factors in Cox proportional hazards multivariate analysis, after inverse probability weighting adjustment. Conclusion These results show that lenvatinib is a good sequential treatment option after progression under regorafenib therapy in unresectable hepatocellular carcinoma patients with better hepatic reserve function.

Real-World Data on Ramucirumab Therapy including Patients Who Experienced Two or More Systemic Treatments: A Multicenter Study

“…Our data suggest that ramucirumab treatment can expect consistent PFS in a wide range of patients. After the approval of atezolizumab and bevacizumab combination therapy, MTAs sequential therapy has become critical for HCC patients [ 19 , 20 , 21 , 22 , 23 ]. There are still clinical questions such as optimal sequential usage of available systemic treatments.…”

Mechanisms of Pharmacoresistance in Hepatocellular Carcinoma: New Drugs but Old Problems

“…A recent study has demonstrated that lenvatinib is a good option as a third-line therapy for those patients progressing under treatments with sorafenib and regorafenib. 71 Combinations of sorafenib with non-TKI molecular inhibitors, such as galunisertib (inhibitor of the transforming growth factor-β [TGF-β] receptor type I) (NCT01246986) 72 and refametinib (MEK inhibitor) (NCT01915589 and NCT01915602), the latter in patients with RAS -mutated HCC, 73 are also being explored.…”

Lenvatinib Plus Immune Checkpoint Inhibitors Improve Survival in Advanced Hepatocellular Carcinoma: A Retrospective Study

“…Therapeutic decisions for late-line patients are mainly determined based on the tumor stage and the underlying liver dysfunction. Several single options evaluated the efficacy and safety of late line HCC compared to the best supportive care or placebo (12,21,22). For example, LEN prolonged OS, offering safety and tolerability in first-line treatment (5), as well as providing a good sequential treatment option after progression in the third line of unresectable HCC patients with better hepatic reserve function (21).…”

“…Several single options evaluated the efficacy and safety of late line HCC compared to the best supportive care or placebo ( 12 , 21 , 22 ). For example, LEN prolonged OS, offering safety and tolerability in first-line treatment ( 5 ), as well as providing a good sequential treatment option after progression in the third line of unresectable HCC patients with better hepatic reserve function ( 21 ). Furthermore, nivolumab was found to be safe in patients with Child-Pugh class B liver dysfunction ( 22 ).…”