Experience of Hepatocellular Cancer Therapy with Multikinase Inhibitors in the Republic of Bashkortostan

Introduction. Hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm of the liver. During the early stages, HCC is asymptomatic, which makes X-ray examination a particularly important diagnostic tool. According to WHO data, the mortality rate from HCC was 782,000 in 2018. HCC is associated with a number of risk factors: a high viral load, liver cirrhosis, detected HBeAg and elevated serum HBsAg levels. Inhibitors of tyrosine kinase receptors increase the overall survival and progression-free survival rates in patients with metastatic HCC. In this article, we conduct an analysis of results of the REFLECT study obtained for Russian patients by the Republican Clinical Oncological Dispensary, Ufa.

Materials and methods. The experimental group included 9 patients (52.9%) receiving Lenvatinib. The control group included 8 patients (47.1%)) underwent therapy with Sorafenib at a dose of 800 mg per day 7 (41.17%) patients had a history of chronic hepatitis, of which hepatitis B and chronic hepatitis C was confirmed in 6 and 1 cases, respectively.

Results and discussion. Over the period from 2017 up to the present, progression-free survival was observed in three patients (17.6%), of which 2 and 1 received Lenvatinib and Sorafenib, respectively. Overall survival was 10.5 months. The median overall survival rate in the experimental and control groups was 9.8 and 11.2 months, respectively. These parameters are considered comparable, provided that the sample was small.

Conclusions. The use of Lenvatinib demonstrated the efficacy comparable to that of Sorafenib in terms of the overall survival rate in patients with inoperable HCC. Lenvatinib allowed statistically and clinically significant improvement in the progression-free survival and time to progression to be achieved. 

1. Ivashkin V.T., Mayev I.V., Kaprin A.D., Agapov M. Yu., Andreev D.N., Vodoleev A.S., et al. Early detection of oncological diseases of the digestive system (guidelines of the Russian gastroenterological association and the Russian association of oncologists for primary care physicians). Rus J Gastroenterol Hepatol Coloproctol. 2019;29 (5):53–74 (In Russ.). DOI: 10.22416/1382-4376-2019-29-5-53-74

2. World health organization. Cancer [Internet]. WHO, 2018 [cited 2020 Sept 9]. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer

3. Kaprin A.D., Starinskiy V.V., Petrova G.V. (eds.) Malignant neoplasms in Russia in 2018 (morbidity and mortality). Moscow: P. Herzen Moscow Oncology Research Institute; 250 p. (In Russ.).

4. Lipatov O.N., Menshikov K.V., Tursumetov D.S., Akhmetgareeva K.T. Immunotherapy of hepatocellular cancer in the Republic of Bashkortostan. Bashkortostan Medical Journal. 2019;14(6):26–30 (In Russ.).

5. Akhmetgareyeva K.T., Lipatov O.N., Menshikov K.V., Sultanbayev A.V. Incidence of primary liver cancer in the Republic of Bashkortostan. In: White nights 2020: proc. of the St. Petersburg International Oncology Forum. St.Petersburg; 2020. P. 22 (In Russ.).

6. Forner A., Reig M., Bruix J. Hepatocellular carcinoma. Lancet 2018;391:1301–14. DOI: 10.1016/S0140-6736(18)30010-2

7. International Classification of Diseases for Oncology (ICD-O). 3rd edition, 1st revision. WHO; 2013. 242 p.

8. Pazgan-Simon M., Simon K.A., Jarowicz E., Rotter K., SzymanekPasternak A., Zuwała-Jagiełło J. Hepatitis B virus treatment in hepatocellular carcinoma patients prolongs survival and reduces the risk of cancer recurrence. Clin Exp Hepatol. 2018;4(3):210–6. DOI: 10.5114/ceh.2018.78127.

9. Levrero M., Zucman-Rossi J. Mechanisms of HBV-induced hepatocellular carcinoma. J Hepatol. 2016;64(1 Suppl):S84–S101. DOI: 10.1016/j.jhep.2016.02.021

10. Brito A.F., Abrantes A.M., Tralhão J.G., Botelho M.F. Targeting Hepatocellular Carcinoma: What did we Discover so Far? Oncol Rev. 2016;10(2):302. DOI: 10.4081/oncol.2016.302

11. Lazarevich N.L., Krivtsova О.M., Skovorodnikova P.A. Molecular genetic features of the clinical prognosis of HСС. Malignant tumours. 2016;(4, Suppl. 1):40–5 (In Russ.). DOI: 10.18027/2224-5057-2016-4s1-40-45

12. Kieran M.W., Kalluri R., Cho Y.J. The VEGF pathway in cancer and disease: responses, resistance, and the path forward. Cold Spring Harb Perspect Med. 2012;2(12):a006593. DOI: 10.1101/cshperspect.a006593

13. Breder V.V., Balakhnin P.V., Virshke E.R., Kosirev V.Yu., Ledin E.S., Petkau V.V. Practical guidelines on drug treatment for hepatocellular carcinoma. Malignant tumours. 2019;9:(3, Suppl. 2):420–38. DOI: 10.18027/2224-5057-2019-9-3s2-420-438

14. Ishihara S., Onoda N., Noda S., Asano Y., Tauchi Y., Morisaki T., et al. Sorafenib inhibits vascular endothelial cell proliferation stimulated by anaplastic thyroid cancer cells regardless of BRAF mutation status. Int J Oncol. 2019;55(5):1069–76. DOI: 10.3892/ijo.2019.4881

15. Llovet J.M., Ricci S., Mazzaferro V., Hilgard Ph., Gane E., Blanc J.-F., et al. Sorafenib in Advanced Hepatocellular Carcinoma. N Engl J Med. 2008;359:378–90. DOI: 10.1056/NEJMoa0708857

16. Kudo M., Finn R.S., Qin S., Kwang-Hyub Han, Ikeda K., Piscaglia F., et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163–73. DOI: 10.1016/S0140-6736(18)30207-1

17. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–24. DOI: 10.3322/caac.21492