Late Combination of Transarterial Chemoembolization with Apatinib and Camrelizumab for Unresectable Hepatocellular Carcinoma is Superior to Early Combination

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2022 Mar 29

PMID 35346114

Authors

Shuguang Ju

Chen Zhou

Junwen Hu

Yingliang Wang

Chaoyang Wang

Jiacheng Liu

Chongtu Yang

Songjiang Huang

Tongqiang Li

Yang Chen

Yaowei Bai

Wei Yao

Bin Xiong

Affiliations

Soon will be listed here.

Abstract

Objective: The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it.

Methods: In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS.

Results: A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8-30.5 months) and the median PFS was 15.7 months (95% CI: 14.7-16.6 months). The ORR was 58.8% (95% CI: 47.2-69.6) and DCR reached 81.2% (95% CI: 71.0-89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060-0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184-0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed.

Conclusion: TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination.

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References

Meng X, Chen B, Huang J, Huang W, Cai M, Zhou J . Early prediction of survival in hepatocellular carcinoma patients treated with transarterial chemoembolization plus sorafenib. World J Gastroenterol. 2018; 24(4):484-493. PMC: 5787783. DOI: 10.3748/wjg.v24.i4.484. View

Kudo M, Ueshima K, Ikeda M, Torimura T, Tanabe N, Aikata H . Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2019; 69(8):1492-1501. PMC: 7398460. DOI: 10.1136/gutjnl-2019-318934. View

Compagnone G, Giampalma E, Domenichelli S, Renzulli M, Golfieri R . Calculation of conversion factors for effective dose for various interventional radiology procedures. Med Phys. 2012; 39(5):2491-8. DOI: 10.1118/1.3702457. View

Raoul J, Sangro B, Forner A, Mazzaferro V, Piscaglia F, Bolondi L . Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev. 2010; 37(3):212-20. DOI: 10.1016/j.ctrv.2010.07.006. View

Montasser A, Beaufrere A, Cauchy F, Bouattour M, Soubrane O, Albuquerque M . Transarterial chemoembolisation enhances programmed death-1 and programmed death-ligand 1 expression in hepatocellular carcinoma. Histopathology. 2020; 79(1):36-46. DOI: 10.1111/his.14317. View

Sieghart W, Hucke F, Pinter M, Graziadei I, Vogel W, Muller C . The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology. 2013; 57(6):2261-73. DOI: 10.1002/hep.26256. View

Huang J, Xu B, Mo H, Zhang W, Chen X, Wu D . Safety, Activity, and Biomarkers of SHR-1210, an Anti-PD-1 Antibody, for Patients with Advanced Esophageal Carcinoma. Clin Cancer Res. 2018; 24(6):1296-1304. DOI: 10.1158/1078-0432.CCR-17-2439. View

Terzi E, Terenzi L, Venerandi L, Croci L, Renzulli M, Mosconi C . The ART score is not effective to select patients for transarterial chemoembolization retreatment in an Italian series. Dig Dis. 2014; 32(6):711-6. DOI: 10.1159/000368007. View

Xu J, Shen J, Gu S, Zhang Y, Wu L, Wu J . Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial. Clin Cancer Res. 2020; 27(4):1003-1011. DOI: 10.1158/1078-0432.CCR-20-2571. View

10.

Zheng L, Fang S, Wu F, Chen W, Chen M, Weng Q . Efficacy and Safety of TACE Combined With Sorafenib Plus Immune Checkpoint Inhibitors for the Treatment of Intermediate and Advanced TACE-Refractory Hepatocellular Carcinoma: A Retrospective Study. Front Mol Biosci. 2021; 7:609322. PMC: 7843459. DOI: 10.3389/fmolb.2020.609322. View

11.

Kiess A, Wolchok J, Barker C, Postow M, Tabar V, Huse J . Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. Int J Radiat Oncol Biol Phys. 2015; 92(2):368-75. PMC: 4955924. DOI: 10.1016/j.ijrobp.2015.01.004. View

12.

Cao F, Yang Y, Si T, Luo J, Zeng H, Zhang Z . The Efficacy of TACE Combined With Lenvatinib Plus Sintilimab in Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study. Front Oncol. 2022; 11:783480. PMC: 8721033. DOI: 10.3389/fonc.2021.783480. View

13.

Khan K, Kerbel R . Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa. Nat Rev Clin Oncol. 2018; 15(5):310-324. DOI: 10.1038/nrclinonc.2018.9. View

14.

Renzulli M, Golfieri R . Proposal of a new diagnostic algorithm for hepatocellular carcinoma based on the Japanese guidelines but adapted to the Western world for patients under surveillance for chronic liver disease. J Gastroenterol Hepatol. 2015; 31(1):69-80. DOI: 10.1111/jgh.13150. View

15.

Sanmamed M, Chen L . A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Cell. 2018; 175(2):313-326. PMC: 6538253. DOI: 10.1016/j.cell.2018.09.035. View

16.

Greten T, Mauda-Havakuk M, Heinrich B, Korangy F, Wood B . Combined locoregional-immunotherapy for liver cancer. J Hepatol. 2019; 70(5):999-1007. PMC: 6462230. DOI: 10.1016/j.jhep.2019.01.027. View

17.

Benson A, DAngelica M, Abbott D, Anaya D, Anders R, Are C . Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021; 19(5):541-565. DOI: 10.6004/jnccn.2021.0022. View

18.

Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M . Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer. 2021; 9(6):682-720. PMC: 7768108. DOI: 10.1159/000509424. View

19.

Xiong B, Feng G, Luo S, Liang H, Qiu L, Zheng C . Changes of CD4(+) CD25 (+) regulatory T cells in peripheral blood in patients with hepatocellular carcinoma before and after TACE. J Huazhong Univ Sci Technolog Med Sci. 2008; 28(6):645-8. DOI: 10.1007/s11596-008-0606-7. View

20.

Meng X, Wu T, Hong Y, Fan Q, Ren Z, Guo Y . Camrelizumab plus apatinib as second-line treatment for advanced oesophageal squamous cell carcinoma (CAP 02): a single-arm, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022; 7(3):245-253. DOI: 10.1016/S2468-1253(21)00378-2. View