Transarterial Chemoembolization Combined with Apatinib for Treatment of Advanced Hepatocellular Carcinoma: Analysis of Survival and Prognostic Factors

Abstract

Objective

Apatinib is a novel inhibitor of vascular endothelial growth factor receptor-2. The goal of this study was to evaluate overall survival (OS) after a combination of transarterial chemoembolization (TACE) and apatinib in patients with advanced hepatocellular carcinoma (HCC) and to identify the factors affecting patient survival.

Methods

Fifty-one patients with advanced HCC who received TACE in combination with apatinib in our hospital from June 2015 to May 2017 were enrolled. The OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. The log-rank test and Cox regression model were used to determine the factors affecting OS.

Results

The median OS and PFS of the patients were 15 months and 10 months, respectively. The 1-, 2-, and 3-year survival rates were 64.7%, 23.5%, and 1.8%, respectively. Univariate survival analysis showed that patients with Child-Pugh A (P=0.006), reduction rate of proper hepatic artery (P=0.016), hand-foot syndrome (P=0.005), secondary hypertension (P=0.050), and without ascites (P=0.010) had a better OS. Multivariate analysis showed that hand-foot syndrome (P=0.014), secondary hypertension (P=0.017), and reduction rate of proper hepatic artery (P=0.025) were independent predictors of better OS.

Conclusion

TACE combined with apatinib is a promising treatment for advanced HCC. Hand-foot syndrome, secondary hypertension, and the reduction rate of proper hepatic artery were associated with a better OS.

Keywords

chemoembolization / therapeutic / apatinib / molecular targeted therapy / survival / factor analysis / statistical

References

[1] FornerA, ReigM, BruixJ. Hepatocellular carcinoma. Lancet, 2018, 391(10127): 1301-1314

[2] ParkJW, ChenM, ColomboM, et al.. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int, 2015, 35(9): 2155 2166

[3] BargelliniI, FlorioF, GolfieriR, et al.. Trends in utilization of transarterial treatments for hepatocellular carcinoma: results of a survey by the Italian Society of Interventional Radiology. Cardiovasc Intervent Radiol, 2017, 37(4): 438-444

[4] GabaRC, LokkenRP, HickeyRM, et al.. Quality Improvement Guidelines for Transarterial Chemoembolization and Embolization of Hepatic Malignancy. J Vasc Interv Radiol, 2017, 28(9): 1210-1223

[5] LiangB, ZhengCS, FengGS, et al.. Correlation of hypoxia-inducible factor 1alpha with angiogenesis in liver tumors after transcatheter arterial embolization in an animal model. Cardiovasc Intervent Radiol, 2010, 33(4): 806-812

[6] ParkJW, KimYJ, KimDY, et al.. Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial. J Hepatol, 2019, 70(4): 684-691

[7] DingJ, ChenX, GaoZ, et al.. Metabolism and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor apatinib in humans. Drug Metab Dispos, 2013, 41(6): 1195-1210

[8] LiangQ, KongL, DuY, et al.. Antitumorigenic and antiangiogenic efficacy of apatinib in liver cancer evaluated by multimodality molecular imaging. Exp Mol Med, 2019, 51(76): 1-11

[9] YangC, QinS. Apatinib targets both tumor and endothelial cells in hepatocellular carcinoma. Cancer Med, 2018, 7(9): 4570-4583

[10] YangZ, ChenG, CuiY, et al.. The safety and efficacy of TACE combined with apatinib on patients with advanced hepatocellular carcinoma: a retrospective study. Cancer Biol Ther, 2019, 20(3): 321-327

[11] LuW, JinXL, YangC, et al.. Comparison of efficacy between TACE combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma: A single-center randomized controlled trial. Cancer Biol Ther, 2017, 18(6): 433-438

[12] ChenS, YuW, ZhangK. Comparison of the efficacy and safety of transarterial chemoembolization with and without apatinib for the treatment of BCLC stage C hepatocellular carcinoma. BMC Cancer, 2018, 18(1): 1131

[13] ZhuY, FengB, MeiL, et al.. Clinical efficacy of TACE combined with Apatinib in the treatment of advanced hepatocellular carcinoma. J BUON, 2019, 24(2): 608-614

[14] FanW, YuanG, FanH, et al.. Apatinib combined with transarterial chemoembolization in patients with hepatocellular carcinoma and portal vein tumor thrombus: a multicenter retrospective study. Clin Ther, 2019, 41(8): 1463-1476

[15] KanX, LiangB, ZhouG, et al.. Transarterial Chemoembolization Combined with Apatinib for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis. Front Oncol, 2020, 7(10): 970

[16] European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol, 2018, 69(1): 182-236

[17] ZhouJ, SunHC, WangZ, et al.. Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition). Liver Cancer, 2018, 7(3): 235-260

[18] ScottLJ. Apatinib: A Review in Advanced Gastric Cancer and Other Advance Cancers. Drugs, 2018, 78: 747-758

[19] Qiu L, Shukui Q, Shanzhi G. Apatinib as second-line therapy in Chinese patients with advanced hepatocellular carcinoma: a randomized, placebo-controlled, doubleblind, phase 3 study. 2020, ASCO Annual Meeting Symposium: 303249

[20] KokVC, ChenY, ChenY, et al.. Sorafenib with Transarterial Chemoembolization Achieves Improved Survival vs. Sorafenib Alone in Advanced Hepatocellular Carcinoma: A Nationwide Population-Based Cohort Study. Cancers (Basel), 2019, 11(7): 985

[21] ChienSC, ChenCY, ChengPN, et al.. Combined Transarterial Embolization/Chemoembolization-Based Locoregional Treatment with Sorafenib Prolongs the Survival in Patients with Advanced Hepatocellular Carcinoma and Preserved Liver Function: A Propensity Score Matching Study. Liver Cancer, 2019, 8(3): 186-202

[22] SatoY, NishiofukuH, YasumotoT, et al.. Multicenter Phase II Clinical Trial of Sorafenib Combined with Transarterial Chemoembolization for Advanced Stage Hepatocellular Carcinomas (Barcelona Clinic Liver Cancer Stage C): STAB Study. J Vasc Interv Radiol, 2018, 29(8): 1061-1067

[23] LiuJ, XieS, DuanX, et al.. Assessment of efficacy and safety of the transcatheter arterial chemoembolization with or without apatinib in the treatment of large hepatocellular carcinoma. Cancer Chemother Pharmacol, 2020, 85(1): 69-76

[24] ZhouC, YaoQ, ZhangH, et al.. Combining transcatheter arterial embolization with iodized oil containing Apatinib inhibits HCC growth and metastasis. Sci Rep, 2020, 10(1): 2964

[25] NiJY, KongJ, SunHL, et al.. Prognostic Factors for Survival After Transarterial Chemoembolization Combined with Sorafenib in the Treatment of BCLC Stage B and C Hepatocellular Carcinomas. Acad Radiol, 2018, 25(4): 423-429

[26] LiuC, XingW, SiT, et al.. Efficacy and safety of apatinib combined with transarterial chemoembolization for hepatocellular carcinoma with portal venous tumor thrombus: a retrospective study. Oncotarget, 2017, 8(59): 100734-100735

[27] LiuJ, XuJ, ZhangW, et al.. Safety and Efficacy of Drug-Eluting Bead Transarterial Chemoembolization Combined with Apatinib in Patients with Advanced Hepatocellular Carcinoma. Acad. Radiol, 2019, 27(5): 704-709

[28] LiaoZ, LiF, ZhangC, et al.. Phase II trial of VEGFR2 inhibitor apatinib for metastatic sarcoma: focus on efficacy and safety. Exp Mol Med, 2019, 51(3): 1-11

[29] PawlikTM, ReyesDK, CosgroveD, et al.. Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. J Clin Oncol, 2011, 29(30): 3960-3967

[30] PandeyAK, SinghiEK, ArroyoJP, et al.. Mechanisms of VEGF (Vascular Endothelial Growth Factor) Inhibitor-Associated Hypertension and Vascular Disease. Hypertension, 2018, 71(2): e1-e8

[31] SiegelAB, CohenEI, OceanA, et al.. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol, 2008, 26(18): 2992-2998