The multikinase inhibitor lenvatinib should be further investigated in patients with unresectable hepatocellular carcinoma (HCC) and Child-Pugh B liver function, according to data from a post hoc analysis of the phase 3 REFLECT study presented at the 2021 Gastrointestinal Cancers Symposium.
The REFLECT trial (ClinicalTrials.gov identifier: NCT01761266), which compared lenvatinib to standard-of-care sorafenib in patients with unresectable HCC and Child-Pugh A liver function, led to lenvatinib’s approval as a frontline therapy for patients with unresectable HCC in 2018. In former analyses of the trial data, patients treated with lenvatinib were found to benefit from the drug irrespective of baseline liver function, but only patients with an initial Child-Pugh A liver function were eligible to participate in the REFLECT study.
There is an unmet need for patients with Child-Pugh B function, and the data presented at the 2021 Gastrointestinal Cancers Symposium derived from a post hoc analysis that explored efficacy and safety outcomes in patients treated with lenvatinib whose liver function deteriorated to Child-Pugh B within 8 weeks of therapy (landmark) vs those who maintained Child-Pugh A function during the same time period. The evaluation specifically assessed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
In lenvatinib-receiving patients who progressed to Child-Pugh B liver function, the median OS and PFS were 6.8 months and 3.7 months after the 8-week landmark, respectively. Among the patients in this Child-Pugh B subset who received sorafenib, the median OS was 4.5 months and the median PFS was 0.5 months.
The ORR in Child-Pugh B patients treated with lenvatinib was 28.3% with a median duration of treatment of 3.2 months. In the sorafenib group, the ORR was 8.5% and the median duration of treatment was 1.9 months.
Among patients with Child-Pugh A liver function, the ORR was 42.9% in those who received lenvatinib, and 12.9% in patients randomly assigned to sorafenib.
Sixty of the patients randomly assigned to lenvatinib progressed to Child-Pugh B status within the first 8 weeks of treatment while 413 maintained Child-Pugh A status. Of them, the incidence of grade 3 treatment-related adverse events (TRAEs) was 71.7% and 54.7% in the Child-Pugh B and Child-Pugh A subpopulations, respectively. The TRAEs led to treatment discontinuation in 18.3% of patients with Child-Pugh B classification and 7.5% of patients with Child-Pugh A liver function
Jasmine Huynh, MD, who presented the findings, said the analysis was limited by its descriptive nature and the efficacy results consequently cannot be compared between the Child-Pugh A and Child-Pugh B liver function subgroups. However, “the results of this post hoc analysis suggest that patients with unresectable HCC whose liver function deteriorates to Child-Pugh B after initiation of therapy may continue to receive lenvatinib,” Huynh concluded.
Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This clinical trial was supported by Eisai Inc. and Merck Sharp & Dohme Corp.
Huynh J, Cho MT, Jae-Hoon Kim E, et al. Post hoc analysis in patients (pts) with unresectable hepatoceollular carcinoma (uHCC) who progressed to Child-Pugh B (CPB) liver function in the phase III REFLECT study of lenvatinib (LEN). Poster presented at: 2021 Gastrointestinal Cancers Symposium; January 15-17, 2021. Poster 289.
This article originally appeared on Cancer Therapy Advisor