Journal Article
. 2020 Oct; 9(5):613-624.
doi: 10.1159/000508901.

Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

Jaekyung Cheon 1 Hong Jae Chon 2 Yeonghak Bang 3 Neung Hwa Park 1 Jung Woo Shin 1 Kang Mo Kim 4 Han Chu Lee 4 Jooho Lee 5 Changhoon Yoo 3 Baek-Yeol Ryoo 3 
Affiliations
  • PMID: 33083284
  •     30 References
  •     12 citations

Abstract

Introduction/Objective: Lenvatinib demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the randomized phase III REFLECT trial. Considering the discrepancies in patients between clinical trial data and daily practice, an account of practical experience is needed.

Methods: We conducted a multicenter retrospective analysis in which 3 tertiary referral centers participated. A total of 92 patients with advanced HCC treated with lenvatinib between September 2018 and January 2020 were analyzed.

Results: Lenvatinib was used as the first-line therapy for 67 (72.8%) patients, and for 25 (27.2%) patients previously treated with other systemic therapy including immune checkpoint inhibitors. At the time of initiation of lenvatinib, 74 (80.4%) and 18 (19.6%) patients were classified as Child-Pugh A and B, respectively. Thirty-five patients (38.0%) had extensive disease that would have excluded them from the REFLECT trial. In the Child-Pugh A group, the response rate graded according to the Response Evaluation Criteria in Solid Tumors v1.1 was 21.1%, median progression-free survival (PFS) was 4.6 (95% confidence interval [CI] 3.1-6.1) months, and overall survival (OS) was 10.7 (95% CI 4.8-16.5) months for patients treated with first-line lenvatinib (n = 57). With second- or later-line lenvatinib (n = 17), median PFS and OS were 4.1 (95% CI 3.1-5.1) and 6.4 (95% CI 5.1-7.7) months, respectively. In the Child-Pugh B group (n = 18), median PFS and OS were 2.6 (95% CI 0.6-4.6) and 5.3 (95% CI 2.0-8.5) months, respectively. The most common grade 3-4 toxicities were hyperbilirubinemia (n = 8; 8.7%), AST elevation (n = 6; 6.5%), and diarrhea (n = 5; 5.4%) across all study patients.

Conclusions: In this real-world study, lenvatinib was found to be well tolerated and effective in more heterogeneous HCC patient populations.

Keywords: Hepatocellular carcinoma; Lenvatinib; Liver cancer; Real-world conditions.

Sorafenib in advanced hepatocellular carcinoma.
Josep M Llovet, Sergio Ricci, +22 authors, SHARP Investigators Study Group.
N Engl J Med, 2008 Jul 25; 359(4). PMID: 18650514
Highly Cited.
Molecular therapies and precision medicine for hepatocellular carcinoma.
Josep M Llovet, Robert Montal, Daniela Sia, Richard S Finn.
Nat Rev Clin Oncol, 2018 Aug 01; 15(10). PMID: 30061739
Highly Cited. Review.
Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial.
Ann-Lii Cheng, Yoon-Koo Kang, +18 authors, Zhongzhen Guan.
Lancet Oncol, 2008 Dec 20; 10(1). PMID: 19095497
Highly Cited.
Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2016.
Kyu-Won Jung, Young-Joo Won, Hyun-Joo Kong, Eun Sook Lee.
Cancer Res Treat, 2019 Mar 28; 51(2). PMID: 30913865    Free PMC article.
Highly Cited.
Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO.
L-T Chen, E Martinelli, +26 authors, J-Y Douillard.
Ann Oncol, 2020 Feb 19; 31(3). PMID: 32067677
Relative dose intensity over the first four weeks of lenvatinib therapy is a factor of favorable response and overall survival in patients with unresectable hepatocellular carcinoma.
Sakura Kirino, Kaoru Tsuchiya, +18 authors, Namiki Izumi.
PLoS One, 2020 Apr 21; 15(4). PMID: 32310967    Free PMC article.
EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma.
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, European Association for the Study of the Liver.
J Hepatol, 2018 Apr 10; 69(1). PMID: 29628281
Highly Cited. Review.
Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial.
Ann-Lii Cheng, Yoon-Koo Kang, +13 authors, Eric Raymond.
J Clin Oncol, 2013 Oct 02; 31(32). PMID: 24081937
Highly Cited.
Correction to: "Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up".
A Vogel, A Cervantes, +12 authors, E Martinelli.
Ann Oncol, 2020 Jan 29; 30(5). PMID: 31987361
REFLECT-a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset.
Tatsuya Yamashita, Masatoshi Kudo, +17 authors, Hiromitsu Kumada.
J Gastroenterol, 2019 Nov 14; 55(1). PMID: 31720835    Free PMC article.
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).
E A Eisenhauer, P Therasse, +13 authors, J Verweij.
Eur J Cancer, 2008 Dec 23; 45(2). PMID: 19097774
Highly Cited.
Therapeutic potential of lenvatinib for unresectable hepatocellular carcinoma in clinical practice: Multicenter analysis.
Atsushi Hiraoka, Takashi Kumada, +17 authors, Real-life Practice Experts for HCC (RELPEC) Study Group and the HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan).
Hepatol Res, 2018 Aug 26; 49(1). PMID: 30144256
Observational registry of sorafenib use in clinical practice across Child-Pugh subgroups: The GIDEON study.
Jorge A Marrero, Masatoshi Kudo, +15 authors, Riccardo Lencioni.
J Hepatol, 2016 Jul 30; 65(6). PMID: 27469901
Highly Cited.
Important Clinical Factors in Sequential Therapy Including Lenvatinib against Unresectable Hepatocellular Carcinoma.
Atsushi Hiraoka, Takashi Kumada, +27 authors, HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan).
Oncology, 2019 Jul 16; 97(5). PMID: 31307035
Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases.
Jorge A Marrero, Laura M Kulik, +5 authors, Julie K Heimbach.
Hepatology, 2018 Apr 07; 68(2). PMID: 29624699
Highly Cited.
Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study.
Philip J Johnson, Shukui Qin, +24 authors, Ann-Lii Cheng.
J Clin Oncol, 2013 Aug 28; 31(28). PMID: 23980084
Highly Cited.
Prognosis of hepatocellular carcinoma: the BCLC staging classification.
J M Llovet, C Brú, J Bruix.
Semin Liver Dis, 1999 Oct 13; 19(3). PMID: 10518312
Highly Cited.
Clinical features of lenvatinib for unresectable hepatocellular carcinoma in real-world conditions: Multicenter analysis.
Atsushi Hiraoka, Takashi Kumada, +20 authors, Real-life Practice Experts for HCC (RELPEC) Study Group, HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan).
Cancer Med, 2018 Dec 24; 8(1). PMID: 30575325    Free PMC article.
Highly Cited.
Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models.
Masahiro Matsuki, Taisuke Hoshi, +4 authors, Junji Matsui.
Cancer Med, 2018 May 08; 7(6). PMID: 29733511    Free PMC article.
Real-Life Experience of Sorafenib Treatment for Hepatocellular Carcinoma in Korea: From GIDEON Data.
Do Young Kim, Hye Jin Kim, +13 authors, Seung Kew Yoon.
Cancer Res Treat, 2016 Oct 19; 48(4). PMID: 26910470    Free PMC article.
Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial.
Masatoshi Kudo, Richard S Finn, +19 authors, Ann-Lii Cheng.
Lancet, 2018 Feb 13; 391(10126). PMID: 29433850
Highly Cited.
Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial.
Calin Cainap, Shukui Qin, +14 authors, Saied El-Nowiem.
J Clin Oncol, 2014 Dec 10; 33(2). PMID: 25488963    Free PMC article.
Highly Cited.
Comparative analysis of liver functional reserve during lenvatinib and sorafenib for advanced hepatocellular carcinoma.
Takeshi Terashima, Tatsuya Yamashita, +11 authors, Shuichi Kaneko.
Hepatol Res, 2020 Apr 21; 50(7). PMID: 32307874
Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real-world conditions-Multicenter analysis.
Atsushi Hiraoka, Takashi Kumada, +24 authors, Real-life Practice Experts for HCC (RELPEC) Study Group, HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan).
Cancer Med, 2019 May 28; 8(8). PMID: 31127698    Free PMC article.
Highly Cited.
The efficacy and safety of lenvatinib for advanced hepatocellular carcinoma in a real-world setting.
Shuntaro Obi, Takahisa Sato, +15 authors, Masao Omata.
Hepatol Int, 2019 Jan 24; 13(2). PMID: 30671808
Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma.
Susumu Maruta, Sadahisa Ogasawara, +28 authors, Naoya Kato.
Liver Cancer, 2020 Oct 02; 9(4). PMID: 32999866    Free PMC article.
Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma.
Kenji Ikeda, Masatoshi Kudo, +9 authors, Hiromitsu Kumada.
J Gastroenterol, 2016 Oct 06; 52(4). PMID: 27704266    Free PMC article.
Highly Cited.
Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase.
Junji Matsui, Yasuhiro Funahashi, +3 authors, Makoto Asada.
Clin Cancer Res, 2008 Sep 04; 14(17). PMID: 18765537
Highly Cited.
Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child-Pugh A Liver Function: A Proof-Of-Concept Study.
Masatoshi Kudo, Kazuomi Ueshima, +17 authors, Naoshi Nishida.
Cancers (Basel), 2019 Aug 03; 11(8). PMID: 31370183    Free PMC article.
NCCN clinical practice guidelines in oncology: hepatobiliary cancers.
Al B Benson, Thomas A Abrams, +25 authors, Andrew X Zhu.
J Natl Compr Canc Netw, 2009 May 02; 7(4). PMID: 19406039    Free PMC article.
Highly Cited.
A Real-World Comparative Analysis of Lenvatinib and Sorafenib as a Salvage Therapy for Transarterial Treatments in Unresectable HCC.
Jaejun Lee, Pil Soo Sung, +13 authors, Seung Kew Yoon.
J Clin Med, 2020 Dec 30; 9(12). PMID: 33371271    Free PMC article.
Lenvatinib for Hepatocellular Carcinoma: A Literature Review.
Takeshi Hatanaka, Atsushi Naganuma, Satoru Kakizaki.
Pharmaceuticals (Basel), 2021 Jan 10; 14(1). PMID: 33418941    Free PMC article.
Review.
A Comparison of Lenvatinib versus Sorafenib in the First-Line Treatment of Unresectable Hepatocellular Carcinoma: Selection Criteria to Guide Physician's Choice in a New Therapeutic Scenario.
Angelo Dipasquale, Arianna Marinello, Armando Santoro.
J Hepatocell Carcinoma, 2021 Apr 23; 8. PMID: 33884259    Free PMC article.
Review.
Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study.
Changhoon Yoo, Jwa Hoon Kim, +10 authors, Baek-Yeol Ryoo.
Liver Cancer, 2021 May 13; 10(2). PMID: 33977087    Free PMC article.
Overview of lenvatinib as a targeted therapy for advanced hepatocellular carcinoma.
Obaid Rehman, Urooj Jaferi, +4 authors, Ranvir Bhangu.
Clin Exp Hepatol, 2021 Oct 30; 7(3). PMID: 34712825    Free PMC article.
Review.
Posttreatment after Lenvatinib in Patients with Advanced Hepatocellular Carcinoma.
Keisuke Koroki, Naoya Kanogawa, +37 authors, Naoya Kato.
Liver Cancer, 2021 Nov 02; 10(5). PMID: 34721509    Free PMC article.
Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.
Yuan-Hung Kuo, Sheng-Nan Lu, +6 authors, Jing-Houng Wang.
Front Oncol, 2021 Nov 12; 11. PMID: 34760699    Free PMC article.
Is There Still a Place for Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma at the Time of Immunotherapies? A Focus on Lenvatinib.
Marie Decraecker, Caroline Toulouse, Jean-Frédéric Blanc.
Cancers (Basel), 2021 Dec 25; 13(24). PMID: 34944930    Free PMC article.
Review.
Combination of Ablation and Immunotherapy for Hepatocellular Carcinoma: Where We Are and Where to Go.
Kunpeng Wang, Cong Wang, +4 authors, Chong Jin.
Front Immunol, 2022 Jan 04; 12. PMID: 34975896    Free PMC article.
Review.
Efficacy of Lenvatinib and Sorafenib in the Real-World First-Line Treatment of Advanced-Stage Hepatocellular Carcinoma in a Taiwanese Population.
Shou-Wu Lee, Sheng-Shun Yang, +3 authors, Teng-Yu Lee.
J Clin Med, 2022 Mar 11; 11(5). PMID: 35268535    Free PMC article.
Lenvatinib Plus Camrelizumab vs. Lenvatinib Monotherapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study.
Qi Li, Mengran Cao, +9 authors, Jinzhang Chen.
Front Oncol, 2022 Mar 15; 12. PMID: 35280760    Free PMC article.
Recent Progress in Systemic Therapy for Hepatocellular Cancer (HCC).
T Tara Ghaziani, Renumathy Dhanasekaran.
Curr Treat Options Gastroenterol, 2022 May 10; 19(2). PMID: 35530750    Free PMC article.