Lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma

Throughout the last 10 years, liver cancer mortality rate in the Russian Federation consistently exceeded the morbidity rate, which is related to the complexity of early diagnostics, absence of effective screening and oncological alertness of allied-profession doctors. In the situation when late dis...

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Autor principal: L. V. Bolotina
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Publicado: IP Habib O.N. 2020
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spelling oai:doaj.org-article:cb2ff4929a5f4cb3bd687c20f6296f182021-11-30T17:03:34ZLenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma1815-14341815-144210.26442/18151434.2020.3.200353https://doaj.org/article/cb2ff4929a5f4cb3bd687c20f6296f182020-11-01T00:00:00Zhttps://modernonco.orscience.ru/1815-1434/article/viewFile/52651/36090https://doaj.org/toc/1815-1434https://doaj.org/toc/1815-1442Throughout the last 10 years, liver cancer mortality rate in the Russian Federation consistently exceeded the morbidity rate, which is related to the complexity of early diagnostics, absence of effective screening and oncological alertness of allied-profession doctors. In the situation when late disease intelligence does not frequently allow radical treatment, palliative methods remain the only option of survivability enhancement and improving the patients quality of life. Lenvatinib was approved as the first-line drug in the treatment of unresectable hepatocellular carcinoma based on the data of the REFLECT trial, in which the drug demonstrated achieving the patients overall survival (OS) comparable to the activity of sorafenib (13.6 months for lenvatinib vs 12.3 months for sorafenib; hazard ratio HR 0.92; 95% confidence interval CI 0.791.06). At the same time, significant inferiority of lenvatinib was observed for secondary endpoints: progression-free survival PFS (7.4 months for lenvatinib vs 3.7 months for sorafenib; HR 0.66; 95% CI 0.570.77;р0.0001), time to progression (8.9 months for lenvatinib vs 3.7 months for sorafenib; HR 0.63; 95% CI 0.530.73;р0.0001) and objective response rate ORR (24.1% for lenvatinib vs 9.2% for sorafenib). The further analysis of the results of the REFLECT study revealed the additional factors impacting patients survival, such as the level of a-fetoprotein (AFP) before treatment, treatment ORR, performance of subsequent antitumor therapy and procedures after completion of the target first-line therapy. In patients responding to lenvatinib in the first line and further receiving any second-line therapy, the mOS was 25.7 months as compared with the median overall survival (mOS) of 22.3 months in patients responding to sorafenib and receiving further second-line therapy. Additionally, in responders switching from lenvatinib to sorafenib, the mOS was 26.2 months. In the recently published comparative study of lenvatinib and transarterial chemoembolization on the BCLC B stage, inferiority of lenvatinib was demonstrated in terms of OS, PFS and ORR in certain patient categories. Considering the data obtained in the REFLECT population, where in patients achieving the RR to the first-line treatment with lenvatinib and further receiving the local antitumor procedures the mOS increased to 27.2 months (95% CI 20.729.8), prescribing target and locoregional therapy in certain cases in this very sequence is possible. The recently published data about administration of lenvatinib outside of the inclusion criteria for the REFLECT trial, have proved the efficacy and safety of this drug administration in real clinical practice, thus significantly expanding our understanding of the key role of lenvatinib in the first-line treatment of unresectable hepatocellular carcinoma.L. V. BolotinaIP Habib O.N.articlelenvatinibliver cancerhepatocellular carcinoma target therapyhepatocellular carcinoma systemic treatmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282RUСовременная онкология, Vol 22, Iss 3, Pp 142-148 (2020)
institution DOAJ
collection DOAJ
language RU
topic lenvatinib
liver cancer
hepatocellular carcinoma target therapy
hepatocellular carcinoma systemic treatment
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle lenvatinib
liver cancer
hepatocellular carcinoma target therapy
hepatocellular carcinoma systemic treatment
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
L. V. Bolotina
Lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma
description Throughout the last 10 years, liver cancer mortality rate in the Russian Federation consistently exceeded the morbidity rate, which is related to the complexity of early diagnostics, absence of effective screening and oncological alertness of allied-profession doctors. In the situation when late disease intelligence does not frequently allow radical treatment, palliative methods remain the only option of survivability enhancement and improving the patients quality of life. Lenvatinib was approved as the first-line drug in the treatment of unresectable hepatocellular carcinoma based on the data of the REFLECT trial, in which the drug demonstrated achieving the patients overall survival (OS) comparable to the activity of sorafenib (13.6 months for lenvatinib vs 12.3 months for sorafenib; hazard ratio HR 0.92; 95% confidence interval CI 0.791.06). At the same time, significant inferiority of lenvatinib was observed for secondary endpoints: progression-free survival PFS (7.4 months for lenvatinib vs 3.7 months for sorafenib; HR 0.66; 95% CI 0.570.77;р0.0001), time to progression (8.9 months for lenvatinib vs 3.7 months for sorafenib; HR 0.63; 95% CI 0.530.73;р0.0001) and objective response rate ORR (24.1% for lenvatinib vs 9.2% for sorafenib). The further analysis of the results of the REFLECT study revealed the additional factors impacting patients survival, such as the level of a-fetoprotein (AFP) before treatment, treatment ORR, performance of subsequent antitumor therapy and procedures after completion of the target first-line therapy. In patients responding to lenvatinib in the first line and further receiving any second-line therapy, the mOS was 25.7 months as compared with the median overall survival (mOS) of 22.3 months in patients responding to sorafenib and receiving further second-line therapy. Additionally, in responders switching from lenvatinib to sorafenib, the mOS was 26.2 months. In the recently published comparative study of lenvatinib and transarterial chemoembolization on the BCLC B stage, inferiority of lenvatinib was demonstrated in terms of OS, PFS and ORR in certain patient categories. Considering the data obtained in the REFLECT population, where in patients achieving the RR to the first-line treatment with lenvatinib and further receiving the local antitumor procedures the mOS increased to 27.2 months (95% CI 20.729.8), prescribing target and locoregional therapy in certain cases in this very sequence is possible. The recently published data about administration of lenvatinib outside of the inclusion criteria for the REFLECT trial, have proved the efficacy and safety of this drug administration in real clinical practice, thus significantly expanding our understanding of the key role of lenvatinib in the first-line treatment of unresectable hepatocellular carcinoma.
format article
author L. V. Bolotina
author_facet L. V. Bolotina
author_sort L. V. Bolotina
title Lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma
title_short Lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma
title_full Lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma
title_fullStr Lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma
title_full_unstemmed Lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma
title_sort lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma
publisher IP Habib O.N.
publishDate 2020
url https://doaj.org/article/cb2ff4929a5f4cb3bd687c20f6296f18
work_keys_str_mv AT lvbolotina lenvatinibasthekeycomponentoffirstlinetherapyforpatientswithunresectablehepatocellularcarcinoma
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