The therapeutic effect and adverse events of lenvatinib combined with PD-1 inhibitor in the treatment of advanced liver cancer

Abstract

Abstract: Objective To investigate the therapeutic effect and adverse events of Lenvatinib combined with PD-1 inhibitor in the treatment of advanced liver cancer.Methods A retrospective analysis was performed for the clinical data of 48 patients hospitalized with advanced liver cancer from January 1, 2019 to January 1, 2021 who were treated with Lenvatinib combined with Pabolizumab as a PD-1 inhibitor. The treatment outcome of intrahepatic lesions was evaluated with Modified Response Evaluation Criteria in Solid Tumors (mRECIST), during follow-up, and RECISTL1.1 was used to evaluate extrahepatic metastatic lesions. Kaplan-Meier method was used to evaluate the patients' survival time.Results Among the 48 patients with treatment experience, 21 achieved partial response, 15 achieved stabilization, and 12 had disease progression. The resulting Objective response rate was 43.75% and the disease control rate was 75.0%. The median time without disease progression was 7.39 (95% confidence interval 5.88-8.92) months. The incidence rate of adverse events was 52.08%. The most common adverse events were rash (31.25%), fatigue (31.25%) and hypertension (27.08%).Conclusion Lenvatinib combined with PD-1 inhibitor has a marked clinical effect in the treatment of advanced primary liver cancer, with a low incidence rate of serious adverse events It is therefore a safe and effective treatment regimen. This treatment is worthy of clinical promotion.

Key words: Liver neoplasms, Lenvatinib, PD-1 inhibitor

WANG Lu, SUN Xiao-hu, BAI Jing-hui. The therapeutic effect and adverse events of lenvatinib combined with PD-1 inhibitor in the treatment of advanced liver cancer[J]. Chinese Hepatolgy, 2022, 27(8): 891-894.

References

[1] Lee S, Kim S H. Reply to: "Detecting microvascular invasion in HCC with contrast enhanced MRI: Is it a good idea?". J Hepatol, 2018, 68(4): 863-864.
[2] Romero D. Combination set to transform HCC therapy. Nat Rev Clin Oncol, 2020, 17(7):389.
[3] Craig A J, von Felden J, Garcia-Lezana T, et al. Tumour evolution in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol, 2020, 17(3): 139-152.
[4] Song Y, Pan G, Chen L, et al. Loss of ATOH8 Increases Stem Cell Features of Hepatocellular Carcinoma Cells. Gastroenterology, 2015, 149(4): 1068-1081.
[5] Cheng A L, Kang Y K, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase Ⅲ randomised, doubleblind, placebo-controlled trial. Lancet Oncol, 2009, 10(1): 25-34.
[6] Qin S, Bai Y, Lim H Y, et al. Randomized, multicenter, openlabel study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol, 2013, 31(28): 3501-3508.
[7] 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. Lancet, 2018, 391(10126): 1163-1173.
[8] Prieto J, Melero I, Sangro B. Immunological landscape and immunotherapy of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol, 2015, 12(12): 681-700.
[9] Iwai Y, Terawaki S, Ikegawa M, et al. PD-1 inhibits antiviral immunity at the effector phase in the liver. J Exp Med, 2003, 198(1): 39-50.
[10] Gao Q, Wang X Y, Qiu S J, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res, 2009, 15(3): 971-979.
[11] Mazzolini G D, Malvicini M. Immunostimulatory monoclonal antibodies for hepatocellular carcinoma therapy. Trends and perspectives. Medicina (B Aires), 2018, 78(1): 29-32.
[12] Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis, 2010, 30(1): 52-60.
[13] Tai W T, Cheng A L, Shiau C W, et al. Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma. Journal of Hepatology, 2011, 55(5): 1041-1048.
[14] Matsui J, Yamamoto Y, Funahashi Y, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer, 2008, 122(3): 664-671.
[15] Matsui J, Funahashi Y, Uenaka T, et al. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res, 2008, 14(17): 5459-5465.
[16] Okamoto K, Kodama K, Takase K, et al. Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models. Cancer Lett, 2013, 340(1): 97-103.
[17] Zhu X D, Tang Z Y, Sun H C. Targeting angiogenesis for liver cancer: Past, present, and future. Genes Dis, 2020, 7(3): 328-335.
[18] 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. Lancet Oncol, 2018, 19(7): 940-952.
[19] Fukumura D, Kloepper J, Amoozgar Z, et al. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol, 2018, 15(5): 325-340.
[20] 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. PLoS One, 2019, 14(2): e212513.