Objective Response by mRECIST to Initial Lenvatinib Therapy Is an Independent Factor Contributing to Deep Response in Hepatocellular Carcinoma Treated with Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy

Abstract

Objective: There is limited information regarding the benefits of Lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for unresectable hepatocellular carcinoma (u-HCC). We compared the efficacy and safety of LEN-TACE sequential therapy to LEN monotherapy and investigated the factors contributing to the LEN-TACE sequential therapy deep response. Methods: We enrolled a multi-center cohort of 247 patients with u-HCC treated with LEN between 2018 and 2020. Propensity score matching identified sixty-three matching pairs of patients with well-balanced characteristics. We retrospectively compared the clinical outcomes, including overall survival (OS), progression-free survival (PFS), and incidence of adverse events (AEs), between the LEN-TACE and LEN monotherapy groups. Additionally, we evaluated the tumor response, change in albumin-bilirubin (ALBI) score, factors affecting PFS and OS, and independent predictors contributing to the LEN-TACE sequential therapy deep response. In this study, at eight weeks after resumption of LEN after initial TACE, "deep response" was defined as achieving CR or PR on mRECIST, and at least a 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters as the reference. Results: The OS and PFS in the LEN-TACE group were significantly higher than those in the LEN monotherapy group (P = 0.002 and P = 0.037, respectively). The incidence of AEs related to LEN was not significantly different between the two groups. In LEN-TACE sequential therapy, the objective response rate was 61.9%, and the disease control rate was 74.6%, according to the mRECIST criteria. No significant change in the ALBI score was observed during sequential LEN-TACE therapy. Multivariable analyses revealed that deep response was independently associated with the outcome of the initial response to LEN by mRECIST: PR (odds ratio: 13.75, 95% CI: 0.41–1.32, P <0.001). Conclusions: LEN-TACE sequential therapy may provide more clinical benefits than LEN monotherapy in u-HCC patients who responded to initial LEN treatment. Objective response according to mRECIST to initial LEN is an independent factor contributing to LEN-TACE sequential therapy deep response.

Clinical Effect of Lenvatinib Re-Administration after Transcatheter Arterial Chemoembolization in Patients with Intermediate Stage Hepatocellular Carcinoma

“…These reports differed from our study in the background of the HCC BCLC stage or the comparison of the treatment method (drug, TACE, etc.). Kuroda et al reported that LEN-TACE sequential therapy might provide more clinical benefits than LEN monotherapy in patients with unresectable HCC, including BCLC-C [ 18 ]. TACE was performed after assessing the therapeutic effect at 8 weeks after LEN treatment.…”

Postprogression treatment of lenvatinib plus PD‐1 inhibitor in advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy

“…Responses was be assessed by the same imaging technology used at baseline, per modified Response Evaluation Criteria in Solid Tumors criteria, by two radiologists (reader 1, S.L., and reader 2, C.A., with 10 years of experience in abdominal imaging). 22 Early response (ER) was defined as OR occurring within 2 months of HAIC treatment. For those that were defined as having progressive disease, we administered the recommended lenvatinib (Eisai Co., Ltd, Tokyo, Japan) based on previous reports that it effectively improves prognosis.…”

“…The responses to HAIC were divided into OR including complete response and partial response, as well as non‐OR including stable disease and progressive disease. Responses was be assessed by the same imaging technology used at baseline, per modified Response Evaluation Criteria in Solid Tumors criteria, by two radiologists (reader 1, S.L., and reader 2, C.A., with 10 years of experience in abdominal imaging) 22 . Early response (ER) was defined as OR occurring within 2 months of HAIC treatment.…”

Efficacy and safety of transarterial chemoembolization plus lenvatinib in the treatment of advanced hepatocellular carcinoma: A meta-analysis

“…A total of 573 articles were retrieved, and 244 repeated articles were excluded by title, year of publication, and author information. Then after reading abstracts and full-text screening, 311 articles that did not meet the criteria were excluded and finally included 18 studies [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] (Fig. 1).…”

“…Seven studies [9,10,[13][14][15][16]18] provided 6-month, 12-month, and 18-month PFS rate data, of which 3 studies [9,14,18] were TACE plus lenvatinib versus TACE alone, and the other 4 studies [10,13,15,16] were TACE plus lenvatinib versus lenvatinib alone.…”