Predictive and prognostic factors in HCC patients treated with lenvatinib

Abstract

Abstract: Lenvatinib and sorafenib are ⅠA recommended as first-line drugs for systemic treatment of advanced hepatocellular carcinoma, which of them are tyrosinase inhibitors. Sorafenib has been the only standard treatment of advanced liver cancer for 10 years in China. However, due to the overall objective response rate of SHARP trial, REFLECT trial was 2.3%, 9.8%, respectively and the high incidence of adverse reactions, it is limited in the treatment of advanced hepatocellular carcinoma. Lenvatinib has been the first-line drug in China since 2018, and its experience is still insufficient. However, based on the Chinese subgroup analysis of REFLECT study (phaseⅢnon inferiority study), the superiority over sorafenib in objective response rate is confirmed. Due to individual difference, tumor heterogeneity, the dose reduction or discontinuation resulting from adverse reactions, the efficacy varies a lot. Therefore, it is particularly important to predict the efficacy of lenvatinib in patients with advanced liver cancer and has become a new research hotspot. This review discusses the possible predictive factors of the effect of lenvatinib in the treatment of advanced liver cancer, in order to optimize the suitable candidates, improve the efficacy of lenvatinib, and guide the clinical experience of lenvatinib.

Key words: Advanced liver cancer, Lenvatinib, Prognostic factors, Predictive factor

Yu Minghua, Li Wei, Ding Xiaoyan, Chen Jinglong. Predictive and prognostic factors in HCC patients treated with lenvatinib[J]. Electronic Journal of Liver Tumor, 2021, 8(2): 47-52.

References

[1] GLOBAL BURDEN OF DISEASE CANCER COLLABORATION, FITZMAURICE C, AKINYEMIJU TF, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability- adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study[J]. JAMA Oncol, 2017, 3(4): 524-548.
[2] BRAY F, FERLAY J, SOERJOMATARAM I, et al.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[3] 冉建朝,王乐,张玥,等.中国人群肝癌所致DALYs疾病负担:1990~2016年长期分析及预测[J].中国循证医学杂志,2018,18(5): 401-409.
[4] LLOVET JM, RICCI S, MAZZAFERRO V, et al.Sorafenib in advanced hepatocellular carcinoma[J]. NEngl J Med, 2008, 359(4): 378-390.
[5] KUDO M, FINN R S, QIN S, et al.Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial[J]. Lancet, 2018, 391(10126): 1163-1173.
[6] KAWAMURA Y, IKEDA K, HIRAKAWA M, et al.New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma[J]. Hepatol Res, 2010, 40(10): 1006-1014.
[7] KAWAMURA Y, KOBAYASHI M, SHINDOH J, et al.Pretreatment Heterogeneous Enhancement Pattern of Hepatocellular Carcinoma May Be a Useful New Predictor of Early Response to Lenvatinib and Overall Prognosis[J]. Liver Cancer, 2020, 9(3): 275-292.
[8] LASSAU N, BONASTRE J, KIND M, et al.Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study[J]. Invest Radiol, 2014, 49(12): 794-800.
[9] FRAMPAS E, LASSAU N, ZAPPA M, et al.Advanced Hepatocellular Carcinoma: early evaluation of response to targeted therapy and prognostic value of Perfusion CT and Dynamic Contrast Enhanced-Ultrasound. Preliminary results[J]. Eur J Radiol, 2013, 82(5): 205-211.
[10] KUORDA H, ABE T, FUJIWARA Y, et al.Change in arterial tumor perfusion is an early biomarker of lenvatinib efficacy in patients with unresectable hepatocellular carcinoma[J]. World J Gastroenterol, 2019, 25(19): 2365-2372.
[11] SEO S, HATANOE, HIGASHI T, et al.Fluorine-18 fluorodeoxyglucose positron emission tomography predicts tumor differentiation, P-glycoprotein expression, and outcome after resection in hepatocellularcarcinoma[J]. ClinCancer Res, 2007, 13(2): 427-433.
[12] KAWAMURA Y, KOBAYASHI M, SHINDOH J,et al.F-Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma as a Useful Predictor of an Extremely Rapid Response to Lenvatinib[J]. Liver Cancer, 2020, 9(1): 84-92.
[13] KODAMA K, KAWAOKAT, NAMBA M, et al.Correlation between Early Tumor Marker Response and Imaging Response in Patients with Advanced Hepatocellular Carcinoma Treated with Lenvatinib[J]. Oncology, 2019, 97(2): 75-81.
[14] SAEKI I, YAMASAKI T, YAMASHITA S, et al.Early Predictors of Objective Response in Patients with Hepatocellular Carcinoma Undergoing Lenvatinib Treatment[J]. Cancers, 2020, 12(4): 779.
[15] CREMOLINI C, LOUPAKIS F, ANTONIOTTI C, et al.Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest[J]. Ann Oncol, 2015, 26(2): 1188-1194.
[16] MARINELLI D, MAZZOTTA M, SCALERA S, et al.KEAP1-driven co-mutations in lung adenocarcinoma unresponsive to immunotherapy despite high tumor mutational burden[J]. Ann Oncol, 2020, 31(12): 1746-1754.
[17] HEINEMANN V, STINTZING S, MODEST DP, et al.Early tumour shrinkage (ETS) and depth of response (DpR) in the treatment of patients with metastatic colorectal cancer (mCRC)[J]. Eur J Cancer, 2015, 51(14): 1927-1936.
[18] TAKAHASHI A, MORIGUCHI M, SEKO Y,et al.Early Tumor Shrinkage as a Predictive Factor for Outcomes in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Analysis[J]. Cancers (Basel), 2020, 12(3): 754
[19] KUNIMOTO H, SHAKADO S, TANAKA T, et al.Reduction in Tumor Stain at 2 Weeks after Treatment Initiation Is a Predictor of the Efficacy of Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma[J]. Oncology, 2020, 98(11): 779-786.
[20] 王磊,陈欣菊. FGF19/FGFR4信号通路在肝细胞癌中的研究进展[J].现代肿瘤医学,2019,27(16):2949-2954.
[21] YAMAUCHI M, ONO A, ISHIKAWA A, et al.Tumor Fibroblast Growth Factor Receptor 4 Level Predicts the Efficacy of Lenvatinib in Patients With Advanced Hepatocellular Carcinoma[J]. Clin Transl Gastroenterol, 2020, 11(5): 179.
[22] 伍代朝,陈林,陈永恒,等.靶向FGFR4的抗肿瘤药物研究进展[J].肿瘤防治研究,2017,44(1):61-65.
[23] ESWARAKUMAR VP, LAX I, SCHLESSINGER J, et al.Cellular signaling by fibroblast growth factor receptors[J]. Cytokine Growth Factor Rev, 2005, 16(2): 139-149.
[24] GAUGLHOFER C, PAUR J, SCHROTTMAIER WC, et al.Fibroblast growth factor receptor 4: A putative key driver for the aggressive phenotype of hepatocellular carcinoma[J]. Carcinogenesis, 2014, 35(10): 2331-2338.
[25] SCHMIDT B, WEI L, DEPERALTA DK, et al.Molecular subclasses of hepatocellular carcinoma predict sensitivity to fibroblast growth factor receptor inhibition[J]. Int J Cancer, 2016,138(6): 1494-1505.
[26] CANCER GENOMEATLAS RESEARCH NETWORK. Comprehensive and integrative genomic characterization of hepatocellular carcinoma[J]. Cell, 2017, 169(7): 1327-1331.
[27] HAVRILESKYL J, REINER M, MORROWP K, et al.A review of relative dose intensity and survival in patients with metastatic solid tumors[J]. Crit Rev. 2015, 93(3): 203-210.
[28] KIRINO S, TSUCHIYA K, KUROSAKI M, et al.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[J]. PLoS One, 2020, 15(4): 231828.
[29] ESO Y, NAKANO S, MISHIMAN M, et al.Dose Intensity/Body Surface Area Ratio is a Novel Marker Useful for Predicting Response to Lenvatinib against Hepatocellular Carcinoma[J]. Cancers, 2019, 12(1): 49.
[30] UCHIKAWA S, KAWAOKA T, NAMBA M, et al.Skeletal Muscle Loss during Tyrosine Kinase Inhibitor Treatment for Advanced Hepatocellular Carcinoma Patients[J]. Liver Cancer, 2019, 9(2): 1-8.
[31] UOJIMA H, CHUMA M, TANAKA Y, et al.Skeletal Muscle Mass Influences Tolerability and Prognosis in Hepatocellular Carcinoma Patients Treated with Lenvatinib[J]. Liver Cancer, 2020, 9(2): 193-206.
[32] CRUZ-JENTOFT AJ, BAHATG, BAUER J, et al.Sarcopenia: revised European consensus on definition and diagnosis[J]. Age Ageing, 2019, 48(1): 16-31.
[33] ENDO K, KURODA H, KANAZAWA J, et al.Impact of Grip Strength in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib[J]. Cancers, 2020, 12(8): 2146.
[34] TADA T, KUMADA T, HIRAOKA A, et al.Neutrophil-to-lymphocyte ratio is associated with survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib[J]. Liver International, 2020, 40(4): 968-976.
[35] LUE A, SERRANO MT, BUSTAMANTE FJ, et al.Neutrophil‐to‐lymphocyte ratio predicts survival in European patients with hepatocellular carcinoma administered sorafenib[J]. Oncotarget, 2017, 8(61): 103077-103086.
[36] HONG YM, YOON KT, HWANG TH, et al.Changes in the neutrophil‐to‐lymphocyte ratio predict the prognosis of patients with advanced hepatocellular carcinoma treated with sorafenib[J]. Eur J Gastroenterol Hepatol, 2019; 31(10): 1250-1255.
[37] TADA T, KUMADA T, HIRAOKA A, et al.Platelet-lymphocyte ratio predicts survival in patients with hepatocellular carcinoma who receive lenvatinib: an inverse probability weighting analysis[J]. Eur J Gastroenterol Hepatol, 2021, 32(2): 261-268.
[38] SHIMOSE S, KAWAGUCHI T, IWAMOTO H, et al.Controlling Nutritional Status (CONUT) Score is Associated with Overall Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Cohort Study[J]. Nutrients, 2020, 12(4): 1076.
[39] ONODERA T, GOSEKI N, KOSAKI G.Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients[J]. Nihon Geka Gakkai Zasshi, 1984, 85(9): 1001-1005.
[40] HIRAOKA A, KUMADA T, TADA T,et al.Nutritional Index as Prognostic Indicator in Patients Receiving Lenvatinib Treatment for Unresectable Hepatocellular Carcinoma[J]. Oncology, 2020, 98(5): 1-8.
[41] FINN RS, IKEDA M, ZHU AX, et al.PhaseⅠb Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma[J]. J Clin Oncol, 2020, 38(26): 2960-2970.
[42] 严律南,杨家印.人工智能肝癌临床决策支持系统的开发验证和应用价值[J].中国普外基础与临床杂志,2020,27(9):1052-1056.