Clinical effect of programmed cell death-1 inhibitor combined with lenvatinib in treatment of advanced primary liver cancer and related adverse events

Ying TENG; Xiaoyan DING; Wendong LI; Jinglong CHEN

doi:10.3969/j.issn.1001-5256.2021.03.020

Volume 37 Issue 3

Mar. 2021

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2021 > 37(3): 606-610

PDF( 1942 KB)

Clinical effect of programmed cell death-1 inhibitor combined with lenvatinib in treatment of advanced primary liver cancer and related adverse events

DOI: 10.3969/j.issn.1001-5256.2021.03.020

Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China

Received Date: 2020-09-12
Accepted Date: 2020-10-26
Published Date: 2021-03-20

Abstract

Abstract

Objective To investigate the clinical effect of domestic programmed cell death-1 (PD-1) inhibitor combined with lenvatinib in the treatment of advanced primary liver cancer and related adverse events. Methods A retrospective analysis was performed for the clinical data of 24 patients with advanced primary liver cancer who were treated with domestic PD-1 inhibitor combined with lenvatinib in Beijing Ditan Hospital, Capital Medical University, from January 1, 2019 to April 2, 2020, with 15 patients in the Camrelizumab+lenvatinib group, 7 patients in the Sintilimab+lenvatinib group, and 2 patients in the Toripalimab+lenvatinib group. During follow-up, Modified Response Evaluation Criteria in Solid Tumors was used to evaluate the treatment outcome of intrahepatic lesions, and RECIST1.1 was used to evaluate extrahepatic metastatic lesions. The Kaplan-Meier method was used to evaluate survival time. Results Among the 24 treatment-experienced patients, 11 achieved partial response, 7 achieved a stable disease, and 6 had disease progression, resulting in an objective response rate of 45.8% and a disease control rate of 75.0%. The median time to disease progression was 8.4 (95% confidence interval: 6.89-9.91) months. The incidence rate of adverse events was 54.17%, and the most common adverse events were fatigue (29.17%) and hypertension (25.00%). Conclusion PD-1 inhibitor combined with lenvatinib has a marked clinical effect in the treatment of advanced primary liver cancer, with a low incidence rate of serious adverse events, and thus it is a safe and effective treatment regimen.
- Liver Neoplasms,
- Programmed Cell Death 1 Receptor,
- Lenvatinib,
- Drug-Related Side Effects and Adverse Reactions

FullText(HTML)

References(21)

References

[1]	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. DOI: 10.3322/caac.21492
[2]	ZHENG R, QU C, ZHANG S, et al. Liver cancer incidence and mortality in China: Temporal trends and projections to 2030[J]. Chin J Cancer Res, 2018, 30(6): 571-579. DOI: 10.21147/j.issn.1000-9604.2018.06.01
[3]	LLOVET JM, MONTAL R, SIA D, et al. Molecular therapies and precision medicine for hepatocellular carcinoma[J]. Nat Rev Clin Oncol, 2018, 15(10): 599-616. DOI: 10.1038/s41571-018-0073-4
[4]	GRETEN TF, PAPENDORF F, BLECK JS, et al. Survival rate in patients with hepatocellular carcinoma: A retrospective analysis of 389 patients[J]. Br J Cancer, 2005, 92(10): 1862-1868. DOI: 10.1038/sj.bjc.6602590
[5]	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[J]. Lancet, 2018, 391(10126): 1163-1173. DOI: 10.1016/S0140-6736(18)30207-1
[6]	TOPALIAN SL, HODI FS, BRAHMER JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer[J]. N Engl J Med, 2012, 366(26): 2443-2454. DOI: 10.1056/NEJMoa1200690
[7]	EL-KHOUEIRY AB, SANGRO B, YAU T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial[J]. Lancet, 2017, 389(10088): 2492-2502. DOI: 10.1016/S0140-6736(17)31046-2
[8]	ZHU AX, FINN RS, EDELINE J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): A non-randomised, open-label phase 2 trial[J]. Lancet Oncol, 2018, 19(7): 940-952. DOI: 10.1016/S1470-2045(18)30351-6
[9]	FUKUMURA D, KLOEPPER J, AMOOZGAR Z, et al. Enhancing cancer immunotherapy using antiangiogenics: Opportunities and challenges[J]. Nat Rev Clin Oncol, 2018, 15(5): 325-340. DOI: 10.1038/nrclinonc.2018.29
[10]	KATO Y, TABATA K, KIMURA T, et al. Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8⁺ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway[J]. PLoS One, 2019, 14(2): e0212513. DOI: 10.1371/journal.pone.0212513
[11]	FINN RS, IKEDA M, ZHU AX, et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma[J]. J Clin Oncol, 2020, 38(26): 2960-2970. DOI: 10.1200/JCO.20.00808
[12]	LENCIONI R, LLOVET JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma[J]. Semin Liver Dis, 2010, 30(1): 52-60. DOI: 10.1055/s-0030-1247132
[13]	EISENHAUER EA, THERASSE P, BOGAERTS J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)[J]. Eur J Cancer, 2009, 45(2): 228-247. DOI: 10.1016/j.ejca.2008.10.026
[14]	WANG F, QIN S, SUN X, et al. Reactive cutaneous capillary endothelial proliferation in advanced hepatocellular carcinoma patients treated with camrelizumab: Data derived from a multicenter phase 2 trial[J]. J Hematol Oncol, 2020, 13(1): 47. DOI: 10.1186/s13045-020-00886-2
[15]	HOOS A. Development of immuno-oncology drugs-from CTLA4 to PD1 to the next generations[J]. Nat Rev Drug Discov, 2016, 15(4): 235-247. DOI: 10.1038/nrd.2015.35
[16]	SHEN H, YANG ES, CONRY M, et al. Predictive biomarkers for immune checkpoint blockade and opportunities for combination therapies[J]. Genes Dis, 2019, 6(3): 232-246. DOI: 10.1016/j.gendis.2019.06.006
[17]	FINN RS, RYOO BY, MERLE P, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: A randomized, double-blind, phase Ⅲ trial[J]. J Clin Oncol, 2020, 38(3): 193-202. DOI: 10.1200/JCO.19.01307
[18]	RIVERA LB, MEYRONET D, HERVIEU V, et al. Intratumoral myeloid cells regulate responsiveness and resistance to antiangiogenic therapy[J]. Cell Rep, 2015, 11(4): 577-591. DOI: 10.1016/j.celrep.2015.03.055
[19]	YASUDA S, SHO M, YAMATO I, et al. Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2(VEGFR2) induces synergistic anti-tumour effect in vivo[J]. Clin Exp Immunol, 2013, 172(3): 500-506. DOI: 10.1111/cei.12069
[20]	KIMURA T, KATO Y, OZAWA Y, et al. Immunomodulatory activity of lenvatinib contributes to antitumor activity in the Hepa1-6 hepatocellular carcinoma model[J]. Cancer Sci, 2018, 109(12): 3993-4002. DOI: 10.1111/cas.13806
[21]	CHEN J, HU X, LI Q, et al. Effectiveness and safety of toripalimab, camrelizumab, and sintilimab in a real-world cohort of hepatitis B virus associated hepatocellular carcinoma patients[J]. Ann Transl Med, 2020, 8(18): 1187. DOI: 10.21037/atm-20-6063

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(2) / Tables(2)

Get Citation

PDF

XML

Article Metrics

Article views (887) PDF downloads(71)

Clinical effect of programmed cell death-1 inhibitor combined with lenvatinib in treatment of advanced primary liver cancer and related adverse events

DOI: 10.3969/j.issn.1001-5256.2021.03.020

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content