Analyses of objective response rate, progression‐free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study

Abstract

Aim The aim of this study was to investigate the predictive factors of objective response rate (ORR) and progression‐free survival (PFS), and the correlation of albumin‐bilirubin (ALBI) grade with decreased appetite and fatigue in hepatocellular carcinoma patients treated with lenvatinib. Methods From March 2018 to December 2018, a total of 94 patients was included in this retrospective multicenter study. Results The median age of all patients was 73 years (interquartile range 66–79.3 years), and approximately 78% patients were men. The ALBI grade was 1, 2, and 3 in 27 (28.7%), 64 (68.1%), and three patients (3.2%), respectively. The Barcelona Clinic Liver Cancer stage was early, intermediate, and advanced in one (1.1%), 22 (23.4%), and 71 patients (75.5%), respectively. Best radiological response was determined to complete response, partial response, stable disease, and progressive disease in 0 (0.0%), 24 (30.4%), 38 (48.1%), and 17 patients (21.5%), respectively, giving the ORR of 30.4%. The 3‐, 6‐, and 12‐month PFS was calculated to be 78.7% (95% CI 70.3–87.1%), 46.7% (95% CI 36.1–57.3%), and 17.4% (95% CI 6.6–28.2%). Multivariate analysis showed that the Barcelona Clinic Liver Cancer intermediate stage was shown to be the only significant factor affecting the ORR (odds ratio 3.78, 95% CI 1.14–12.5, P = 0.030) and PFS (hazard ratio 0.49, 95% CI 0.26–0.94, P = 0.030). The incidence of all grades of decreased appetite and fatigue was significantly less in patients with ALBI grade 1 compared with ALBI grade 2 + 3. Conclusions The Barcelona Clinic Liver Cancer intermediate stage was the predictive factor affecting the ORR and PFS, and ALBI grade was a good predictive factor affecting the incidence of fatigue and decreased appetite.

Early Tumor Shrinkage as a Predictive Factor for Outcomes in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Analysis

“…In the present study, median PFS was 5.0 months, which was shorter than that in the phase 3 REFLECT trial, revealing median PFS was 7.4 months in the overall population and 7.2 months in the Japanese subset [18]. However, in real-world settings, median PFS ranging from 4.4 to 5.4 months has been reported, consistent with our results [19,20]. This may be explained by more patients in real-world settings being aged and having low ECOG-PS score and Child-Pugh score compared with the clinical trial.…”

Liver Function Changes in Patients with Hepatocellular Carcinoma Treated with Lenvatinib: Predictive Factors of Progression to Child-Pugh Class B, the Formation of Ascites and the Candidates for the Post-Progression Treatment

“…This is probably because the patients with good liver function and PS were initially received full dose, as shown in Table 7 , resulting in well-preserved liver function and PS after lenvatinib treatment. While dose reduction or starting dose was not influence on the decreased efficacy of sorafenib therapy [ 30 ], relative dose intensity was associated with efficacy of lenvatinib treatment [ 31 , 32 ] and adverse events were manageable in patients with good liver function [ 11 , 12 ]. Therefore, the patients with good liver function were likely to receive initial full dose of lenvatinib, indicating that the initial full dose was found to be significant factor.…”

“…The REFLECT trial [ 8 ] revealed that lenvatinib showed non-inferiority to sorafenib in terms of overall survival (OS) and a statistically significant improvement in the objective response rate (ORR) and progression-free survival (PFS). Lenvatinib has recently become available as the first-line systemic therapy and showed the ORR of 30.4 to 39.0 % and the median PFS of 5.4 to 7.6 months in clinical settings [ 9 , 10 , 11 , 12 ]. Moreover, regorafenib [ 13 ] and cabozantinib [ 14 ] demonstrated efficacy in second-line treatment and ramucirumab [ 15 ] also provide the better outcome in patients with α-fetoprotein (AFP)≧ 400 ng/mL.…”

Therapeutic efficacy of lenvatinib in hepatocellular carcinoma patients with portal hypertension

“…1,19 Other studies reported that AEs related to lenvatinib treatment more frequently occurred in patients with poor liver function (ALBI grade 2 or 3) at the time of lenvatinib initiation. 3,20 It has been verified that preserved liver function (ALBI grade 1) is important to the achievement of a favorable therapeutic response while high dosages were maintained. [3][4][5]21 However, not all patients with deteriorated liver function (ALBI grade 2 or 3) will be contraindicated to lenvatinib.…”

“…However, lenvatinib treatment is not generally recommended for all patients with ALBI grade 2 or 3, because AEs are more severe in such patients than in patients with ALBI grade 1. 3,20 Further studies are required to confirm the strategy of lenvatinib treatment for patients with advanced portal hypertension. For most anticancer drugs, the pharmacokinetic profile of drug exposure in patients with poor liver function has been discussed.…”