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. 2022 Jul 11;11(6):527-539.
doi: 10.1159/000525145. eCollection 2022 Dec.

Real Life Study of Lenvatinib Therapy for Hepatocellular Carcinoma: RELEVANT Study

Andrea Casadei-Gardini  1   2 , Margherita Rimini  3 , Masatoshi Kudo  4 , Shigeo Shimose  5 , Toshifumi Tada  6 , Goki Suda  7 , Myung Ji Goh  8 , Andre Jefremow  9   10 , Mario Scartozzi  11 , Giuseppe Cabibbo  12 , Claudia Campani  13 , Emiliano Tamburini  14 , Francesco Tovoli  15 , Kazuomi Ueshima  4 , Tomoko Aoki  4 , Hideki Iwamoto  5 , Takuji Torimura  5 , Takashi Kumada  2 , Atsushi Hiraoka  16 , Masanori Atsukawa  17 , Ei Itobayashi  18 , Hidenori Toyoda  19 , Naoya Sakamoto  7 , Takuya Sho  7 , Wonseok Kang  20 , Jürgen Siebler  9   10 , Markus Friedrich Neurath  9   10 , Valentina Burgio  2 , Stefano Cascinu  1   2
Affiliations

Real Life Study of Lenvatinib Therapy for Hepatocellular Carcinoma: RELEVANT Study

Andrea Casadei-Gardini et al. Liver Cancer. .

Abstract

Introduction: In the REFLECT trial, lenvatinib was found to be noninferior compared to sorafenib in terms of overall survival. Here, we analyze the effects of lenvatinib in the real-life experience of several centers across the world and identify clinical factors that could be significantly associated with survival outcomes.

Methods: The study population was derived from retrospectively collected data of HCC patients treated with lenvatinib. The overall cohort included western and eastern populations from 23 center in five countries.

Results: We included 1,325 patients with HCC and treated with lenvatinib in our analysis. Median OS was 16.1 months. Overall response rate was 38.5%. Multivariate analysis for OS highlighted that HBsAg positive, NLR >3, and AST >38 were independently associated with poor prognosis in all models. Conversely, NAFLD/NASH-related etiology was independently associated with good prognosis. Median progression-free survival was 6.3 months. Multivariate analysis for progression-free survival revealed that NAFLD/NASH, BCLC, NLR, and AST were independent prognostic factors for progression-free survival. A proportion of 75.2% of patients suffered from at least one adverse effect during the study period. Multivariate analysis exhibited the appearance of decreased appetite grade ≥2 versus grade 0-1 as an independent prognostic factor for worse progression-free survival. 924 patients of 1,325 progressed during lenvatinib (69.7%), and 827 of them had a follow-up over 2 months from the beginning of second-line treatment. From first-line therapy, the longest median OS was obtained with the sequence lenvatinib and immunotherapy (47.0 months), followed by TACE (24.7 months), ramucirumab (21.2 months), sorafenib (15.7 months), regorafenib (12.7 months), and best supportive care (10.8 months).

Conclusions: Our study confirms in a large and global population of patients with advanced HCC, not candidates for locoregional treatment the OS reported in the registration study and a high response rate with lenvatinib.

Keywords: ALBI; Hepatocellular carcinoma; Lenvatinib; Neutrophils to lymphocyte ratio; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Outcome; Second line; Tyrosine kinase inhibitors.

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Conflict of interest statement

A.C.-G. has received grants and personal fees from MSD, Eisai, and Bayer and is an adviser for MSD, Eisai, Bayer, Bristol-Myers Squibb, AstraZeneca, and GSK. M.K. has received grants from Taiho Pharmaceuticals, Chugai Pharmaceuticals, Otsuka, Takeda, Sumitomo Dainippon-Sumitomo, Daiichi Sankyo, AbbVie, Astellas Pharma, and Bristol-Myers Squibb; has received grants and personal fees from MSD, Eisai, and Bayer; and is an adviser for MSD, Eisai, Bayer, Bristol-Myers Squibb, Eli Lilly, and ONO Pharmaceutical. Prof. Kudo is the Editor-in-chief of Liver Cancer. K.U.: she is an Editorial Board Member. A.J.: personal fees from Eisai.

Figures

Fig. 1
Fig. 1
Kaplan-Meier curve for OS and progression-free survival.
Fig. 2
Fig. 2
Kaplan-Meier curve for OS for HBsAg (a), NLR 3 (b), AST (c), NASH-related etiology (d), BCLC stage (e), bilirubin (f), and albumin (g).
See this image and copyright information in PMC

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