Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria

Abstract

AimThis study aimed to determine the efficacy and safety of lenvatinib for patients with unresectable hepatocellular carcinoma (HCC) who did not meet REFLECT eligibility criteria (phase 3 clinical trial).MethodsIn this multicenter retrospective study, patients with unresectable HCC treated with lenvatinib between 2018 and 2019 and had adequate clinical data were included. Objective response rate, progression‐free‐survival (PFS) and safety were evaluated according to meeting or not meeting the REFLECT eligibility criteria and according to the criteria of the REFLECT trial.ResultsOf the 105 patients included, 61% (64 of 105) did not meet the REFLECT eligibility criteria. Safety and median PFS of lenvatinib were similar between the patients who did and those who did not meet the criteria. Among the patients who did not meet the criteria, 28, 27, 14, six, seven and five had a history of tyrosine kinase inhibitor (TKI) treatment, Child–Pugh score B, HCC in ≥50% of the liver, reduced platelet count, bile duct invasion and main portal vein invasion, respectively. The efficacy and safety of lenvatinib for patients with or without Child–Pugh‐score B or HCC in ≥50% of the liver were similar. Although treatment outcome was not significantly different, patients with TKI treatment history tended to have longer median PFS, whereas those with main portal vein invasion tended to have shorter median PFS.ConclusionLenvatinib was effective for patients who did not meet the REFLECT inclusion criteria. However, the treatment outcome may vary according to several factors, such as a history of TKI treatment and tumor invasion.

Lenvatinib for Hepatocellular Carcinoma: A Literature Review

“…Many real-world studies have reported the short-term therapeutic response of lenvatinib, resulting in an ORR of 29.9-53.5%, as assessed by mRECIST [17][18][19][20][21][22][23][24], and 14-25%, as assessed by RECIST ver.1.1 [19,22,25,26]. These findings seemed to be in agreement with the results of phase 2 and 3 studies (Table 1).…”

“…The PFS in patients with and without high burden of intrahepatic lesion was 3.9 months and 5.3 months, respectively; the difference was not statistically significant [22]. According to a previous study that was reported by Sho et al [20], the ORR and PFS were not signficantly differed between the patients who met the REFLECT criteria and those who did not (61.5%, 10.3 months vs. 48.3%, 9.8 months). They also reported that the ORR and PFS did not differ to a statistically significant extent between patients with an experience of TKI therapy and those without (44.4% 11.1 months vs. 56.9%, 9.1 months), the patients with portal vein invasion at the main portal trunk and those without (40.0%, 5.6 months vs. 54.3%, 9.9 months), or the patients with liver occupation of tumor ≥50% and those without (33.3%, 8.6 months vs. 56.3%, 9.9 months) [20].…”

“…Accordingly, lenvatinib was thought to be effective for patients who were excluded according to tumor conditions; however, the number of subjects in these studies was small. Regarding the treatment settings of lenvatinib, the therapeutic efficacy in patients who received lenvatinib as first-line treatment did not differ to a statistically significant extent from that in patients who received lenvatinib as second-line treatment or beyond [20,22,110]. Based on these findings, the administration of lenvatinib as a second-line treatment or beyond may not be inferior to the administration of lenvatinib as first-line treatment.…”

“…PFS was defined as the time from randomization (in phase 3 study) or start of treatment (in real-world studies) to disease progression or death. The median PFS in lenvatinibtreated patients was reported to be 7.3 months (95% confidence interval (CI) 5.6-7.5) in a phase 3 study [12], while some of the retrospective studies reported the median PFS of 4.3-9.8 months [17,18,20,22,23,25,26]. Our retrospective study reported that the BCLC intermediate stage was significantly associated with PFS in a multivariate analysis (median PFS; 8.0 months in intermediate stage, 4.0 months in advanced stage) [18].…”

“…They also reported that the ORR and PFS did not differ to a statistically significant extent between patients with an experience of TKI therapy and those without (44.4% 11.1 months vs. 56.9%, 9.1 months), the patients with portal vein invasion at the main portal trunk and those without (40.0%, 5.6 months vs. 54.3%, 9.9 months), or the patients with liver occupation of tumor ≥50% and those without (33.3%, 8.6 months vs. 56.3%, 9.9 months) [20]. While these studies reported that the efficacy in patients with Child-Pugh class B was not significantly lower in comparison to that in patients with Child-Pugh class A [20,22], one study reported that the ORR in patients with Child-Pugh class B was lower than that in patients with Child-Pugh class A (16.3% vs. 36.5%, p = 0.008) [21].…”