Early Predictors of Objective Response in Patients with Hepatocellular Carcinoma Undergoing Lenvatinib Treatment

Abstract

There are limited reports regarding early predictors of objective response (OR) in patients with hepatocellular carcinoma (HCC) treated with lenvatinib. This retrospective study including 70 patients aimed to investigate the efficacy of hepatic biochemical markers. Changes in tumor marker (alpha-fetoprotein (AFP)/des-gamma-carboxy prothrombin (DCP)) levels and albumin–bilirubin (ALBI) score between the baseline value and that estimated one month after treatment were evaluated. We identified several predictors of OR, including changes in tumor marker levels. The OR rate calculated using modified Response Evaluation Criteria in Solid Tumor (mRECIST) was 41.4%. Response was defined as a reduction in AFP and DCP levels of ≥40% from baseline. OR was significantly associated with AFP response, but not with DCP. Predictors of OR were evaluated in two groups (high-AFP group: baseline AFP ≥ 10 ng/mL; low-AFP group: remaining patients). A multivariate analysis identified AFP response (odds ratio, 51.389; p = 0.001) and ALBI score (odds ratio, 6.866; p = 0.039) as independent predictors of OR in the high-AFP and low-AFP groups, respectively. Changes in the ALBI score indicated deterioration in both responders and non-responders, with a significant difference in non-responders (p = 0.003). AFP response, baseline ALBI score, and change in the ALBI score were early predictors of OR in patients with HCC undergoing lenvatinib treatment.

Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma

“…Several predictors for the efficacy of lenvatinib (4-week relative dose intensity [ 19 ], AFP [ 20 , 21 ], ALBI grade [ 20 , 21 , 22 ], neutrophil-to-lymphocyte ratio [ 23 ], and occurrence of hypothyroidism [ 24 ]) have been reported previously. On radiological evaluation, obtaining OR by mRECIST evaluation has been reported to be an independent predictor of OS with other MTAs [ 25 , 26 , 27 ].…”

Early Changes in Alpha-Fetoprotein Are a Useful Predictor of Efficacy of Atezolizumab plus Bevacizumab Treatment in Patients with Advanced Hepatocellular Carcinoma

“…There have been several reports on the relationship between AFP changes and antitumor response and prognosis after administration of molecular-targeted agents (MTAs), such as sorafenib [7-9] and lenvatinib [11-13], in patients with advanced HCC. Patients with decreased AFP during MTA treatment have been reported to have better antitumor efficacy and prognosis.…”

“…Alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), tumor markers for HCC, are widely used not only for the diagnosis of HCC but also as adjunctive diagnostic tests to evaluate treatment effect because they are minimally invasive and can be measured frequently. Several studies have been reported on the relationship between changes in AFP and DCP after treatment and therapeutic efficacy and prognosis in patients treated with molecular-targeted drugs, such as sorafenib [7-10] and lenvatinib [11-13]. However, the IMbrave150 trial did not report the changes in tumor markers during treatment with atezolizumab plus bevacizumab in detail.…”

Early Alpha-Fetoprotein Response Is Associated With Survival in Patients With HBV-Related Hepatocellular Carcinoma Receiving Lenvatinib

“…For example, previous studies of patients with HCC receiving sorafenib have shown that AFP response is associated with survival, despite differences in AFP criteria for study entry (>20 or >200 ng/ml) and AFP response definitions (21,22). However, few studies have investigated the value of AFP as a biomarker in patients with advanced HCC treated with lenvatinib (23)(24)(25). In particular, a better understanding of the relationship between early AFP response and clinical outcomes in these patients may facilitate decisions on whether to continue lenvatinib treatment.…”