Therapeutic effect of lenvatinib combined with PD-1 inhibitor on unresectable large hepatocellular carcinoma after stereotactic body radiotherapy

Abstract

Abstract: Objective To investigate the short-term efficacy and side effects of lenvatinib combined with PD-1 inhibitor in the treatment of unresectable large hepatocellular carcinoma (LHCC) after stereotactic body radiotherapy (SBRT). Methods Clinical data of 10 LHCC patients treated with lenvatinib combined with PD-1 inhibitor after SBRT were collected. Modified response evaluation criteria in solid tumors (mRECIST) was used to evaluate the therapeutic efficacy, and progression-free survival (PFS) was selected as the main endpoint of the study. Results Ten patients (100%) were responsive to the treatment, 7 (70%) achieved partial response, objective response rate (ORR) was 70%, and disease control rate reached 100%. No typical radiation-induced liver damage occurred, and Child-Pugh score increased in 6 cases (60%). Conclusion After SBRT, lenvatinib combined with PD-1 inhibitor has an ideal short-term efficacy in the treatment of unresectable LHCC, and the toxic and side effects are controllable.

Key words: Hepatocellular carcinoma, Stereotactic body radiatherapy, PD-1, Targeted therapy

WANG Guo-xue, ZHANG Ai-min, WANG Quan, SUN Jing, LI Wen-gang, DUAN Xue-zhang. Therapeutic effect of lenvatinib combined with PD-1 inhibitor on unresectable large hepatocellular carcinoma after stereotactic body radiotherapy[J]. Chinese Hepatolgy, 2021, 26(10): 1091-1095.

References

[1] Yang JD, Hainaut P, Gores GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol, 2019, 16: 589-604.
[2] Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 2019, 394: 1145-1158.
[3] Kim DY, Han KH. Epidemiology and surveillance of hepatocellular carcinoma. Liver Cancer, 2012, 1: 2-14.
[4] Rimassa L, Pressiani T, Merle P. Systemic Treatment Options in Hepatocellular Carcinoma. Liver Cancer, 2019, 8: 427-446.
[5] Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet, 2018, 391:1301-1314.
[6] Waidmann O. Recent developments with immunotherapy for hepatocellular carcinoma. Expert Opin Biol Ther, 2018, 18: 905-910.
[7] Chen Y, Gao M, Huang Z, et al. SBRT combined with PD-1/PD-L1 inhibitors in NSCLC treatment: a focus on the mechanisms, advances, and future challenges. J Hematol Oncol, 2020, 13: 105.
[8] Tubin S, Yan W, Mourad WF, et al. The future of radiation-induced abscopal response: beyond conventional radiotherapy approaches. Future Oncol, 2020, 16: 1137-1151.
[9] Ashrafizadeh M, Farhood B, Eleojo Musa A, et al. Abscopal effect in radioimmunotherapy. Int Immunopharmacol, 2020, 85: 106663.
[10] Perks J, Benedict S. MO-F-BRCD-02: SBRT (Part 2): Physics and Quality Assurance Updates. Med Phys, 2012, 39: 3873.
[11] Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis, 2010, 30: 52-60.
[12] Pan CC, Kavanagh BD, Dawson LA, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys, 2010, 76: S94-100.
[13] Chapman TR, Bowen SR, Schaub SK, et al. Toward consensus reporting of radiation-induced liver toxicity in the treatment of primary liver malignancies: Defining clinically relevant endpoints. Pract Radiat Oncol, 2018, 8: 157-166.
[14] Hoyer M, Roed H, Traberg Hansen A, et al. Phase II study on stereotactic body radiotherapy of colorectal metastases. Acta Oncol, 2006, 45: 823-830.
[15] Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol, 2003, 13: 176-181.
[16] Scheiner B, Kirstein MM, Hucke F, et al. Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort. Aliment Pharmacol Ther, 2019, 49: 1323-1333.
[17] Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet, 2018, 391: 1163-1173.
[18] Bauml JM, Mick R, Ciunci C, et al. Pembrolizumab After Completion of Locally Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer: A Phase 2 Trial. JAMA Oncol, 2019, 5:1283-1290.
[19] Chiang CL, Chan ACY, Chiu KWH, et al. Combined Stereotactic Body Radiotherapy and Checkpoint Inhibition in Unresectable Hepatocellular Carcinoma: A Potential Synergistic Treatment Strategy. Front Oncol, 2019, 9:1157.
[20] Shaverdian N, Lisberg AE, Bornazyan K, et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol, 2017, 18: 895-903.
[21] Saâda-Bouzid E, Defaucheux C, Karabajakian A, et al. Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol, 2017, 28: 1605-1611.
[22] Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med, 2020, 382: 1894-1905.
[23] Walle T, Martinez Monge R, Cerwenka A, et al. Radiation effects on antitumor immune responses: current perspectives and challenges. Ther Adv Med Oncol, 2018, 10:1758834017742575.
[24] Cheng S, Chen M, Cai J, et al. Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus (2018 Edition). Liver Cancer, 2020, 9: 28-40.
[25] Hu Y, Qin T, Li S, et al. Efficacy and Safety of SBRT Combined With Camrelizumab and Apatinib in HCC Patients With PVTT: Study Protocol of a Randomized Controlled Trial. Front Oncol, 2020, 10:1589.
[26] Xu J, Shen J, Gu S, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a non-randomized, open-label, phase 2 trial. Clin Cancer Res, 2021, 27:1003-1011.
[27] Chicas-Sett R, Morales-Orue I, Castilla-Martinez J, et al. Stereotactic Ablative Radiotherapy Combined with Immune Checkpoint Inhibitors Reboots the Immune Response Assisted by Immunotherapy in Metastatic Lung Cancer: A Systematic Review. Int J Mol Sci, 2019, 20:2173.