Eisai's Phase III Trial Results of Anticancer Agent Lenvatinib in Hepatocellular Carcinoma Published in The Lancet
2018年2月12日 - 10:03AM
JCN Newswire (英)
Eisai Co., Ltd. announced that the results of a Phase III study
(REFLECT study, Study 304) of its in-house discovered and developed
anticancer agent lenvatinib mesylate (product names:
Lenvima/Kisplyx, "lenvatinib") in patients with hepatocellular
carcinoma (HCC) have been published in the online version of The
Lancet,(1) which is one of the world's most prestigious medical
journals and was recently ranked second in the world in terms of
Impact Factor. (Lead author: Professor and Chairman Masatoshi Kudo
of Kindai University Faculty of Medicine, Title of paper:
"Lenvatinib versus sorafenib in first-line treatment of patients
with unresectable hepatocellular carcinoma: a randomised phase 3
non-inferiority trial").
The REFLECT study reported on in the paper was a multicenter,
open-label, randomized, global Phase III study comparing the
efficacy and safety of lenvatinib versus sorafenib, a standard
treatment for advanced hepatocellular carcinoma, as a first-line
treatment in patients with unresectable HCC. In this study,
lenvatinib demonstrated a treatment effect on the primary endpoint
of Overall Survival (OS) by statistical confirmation of
non-inferiority to sorafenib. Additionally, lenvatinib showed
highly statistically significant and clinically meaningful
improvements in the secondary endpoints of Progression Free
Survival (PFS), Time To Progression (TTP), and Objective Response
Rate (ORR).
The paper also reported on the results of an exploratory analysis
of the secondary endpoints based on blinded independent imaging
review (IIR). The IIR based on both RECIST1.1, which uses the
traditional assessment of the effect on change in tumor diameter,
and mRECIST, which takes into account areas of tumor necrosis in
addition to the RECIST 1.1 criteria, confirmed similar findings to
the investigators' review (per mRECIST criteria) of extensions in
PFS and TTP as well as an increase in ORR compared to sorafenib
based on lenvatinib's superior reduction in tumor size.
In this study, the five most common adverse events observed in the
lenvatinib arm were hypertension, diarrhea, decreased appetite,
weight loss and fatigue, which is consistent with the known safety
profile of lenvatinib.
Eisai has submitted applications for lenvatinib for the treatment
of HCC in Japan (June 2017), the United States and Europe (July
2017), China (October 2017), Taiwan (December 2017) and other
countries. Eisai remains committed to providing additional clinical
evidence for lenvatinib aimed at maximizing the value of the drug
to patients as it seeks to contribute further to addressing the
diverse needs of, and increasing the benefits provided to, patients
with cancer, their families, and healthcare providers.
About lenvatinib mesylate (generic name, "lenvatinib", product
name: Lenvima / Kisplyx)
Discovered and developed in-house, lenvatinib is an orally
administered multiple receptor tyrosine kinase (RTK) inhibitor with
a novel binding mode that selectively inhibits the kinase
activities of vascular endothelial growth factor (VEGF) receptors
(VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF)
receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other
proangiogenic and oncogenic pathway-related RTKs (including the
platelet-derived growth factor (PDGF) receptor PDGFRalpha; KIT; and
RET) involved in tumor proliferation.
Currently, Eisai has obtained approval for lenvatinib as a
treatment for refractory thyroid cancer in over 50 countries,
including the United States, Japan, in Europe and Asia, under the
brand name Lenvima. Additionally, Eisai has obtained approval for
lenvatinib in combination with everolimus as a treatment for renal
cell carcinoma (second-line) in over 40 countries, including the
United States and in Europe. In Europe, the agent was launched
under the brand name Kisplyx for renal cell carcinoma.
A Phase III study of lenvatinib in separate combinations with
everolimus and pembrolizumab in renal cell carcinoma (first-line)
is underway. A Phase Ib/II study to investigate lenvatinib in
combination with pembrolizumab in select solid tumors (endometrial
cancer, non-small cell lung cancer, renal cell carcinoma,
urothelial cancer, head and neck cancer, and melanoma) and a Phase
Ib study in HCC are also underway. Additionally, a Phase Ib study
to investigate lenvatinib in combination with nivolumab in HCC has
been initiated in Japan.
About the REFLECT Study (Study 304)(1)
The REFLECT study is a multicenter, open-label, randomized, global
Phase III study comparing the efficacy and safety of lenvatinib
versus sorafenib, a standard treatment for advanced hepatocellular
carcinoma (HCC), as a first-line treatment for patients with
unresectable HCC. In the study, 954 patients were randomized in a
1:1 ratio to receive lenvatinib 12 mg (>/=60 kg) or 8 mg (<60
kg) once a day, depending on baseline body weight (n = 478) or
sorafenib 400 mg twice a day (n = 476). Treatment was continued
until disease progression or unacceptable toxicity.
The primary endpoint of the study was OS, with the goal of
demonstrating non-inferiority. Other factors including PFS, TTP,
ORR and Quality of Life (QOL) were assessed as secondary
endpoints.
In this study, the five most common adverse events observed in the
lenvatinib arm were hypertension, diarrhea, decreased appetite,
weight loss and fatigue, which is consistent with the known safety
profile of lenvatinib.
About RECIST (Response Evaluation Criteria In Solid Tumors)
RECIST1.1 is a set of assessment criteria used to evaluate effects
on solid cancers (based on changes in tumor diameter). mRECIST is a
new criteria that takes into account areas of tumor necrosis in
addition to RECIST1.1.
About Hepatocellular Carcinoma (HCC)
Liver cancer is the second-leading cause of cancer death, estimated
to be responsible for 750,000 deaths per year globally.
Additionally, 780,000 cases are newly diagnosed each year.(2) There
is a large regional difference, with about 80% of new cases
occurring in Asian regions, including China and Japan. HCC accounts
for 85% to 90% of liver cancer. Currently, systemic therapies
approved for firstline treatment of HCC are limited, underscoring a
great unmet medical need.
About The Lancet
First published in 1823 and with a history spanning over 190 years,
The Lancet is an influential medical journal that is highly
regarded worldwide.
Impact Factor is based on "2016 Journal Citation Reports, Clarivate
Analytics 2017."
(1) M Kudo, et al. "Lenvatinib versus sorafenib in first-line
treatment of patients with unresectable hepatocellular carcinoma: a
randomised phase 3 non-inferiority trial" The Lancet, 2018
(2) GLOBOCAN2012: Estimated Cancer Incidence, Mortality and
Prevalence Worldwide in 2012. http://globocan.iarc.fr/
About Eisai
Eisai Co., Ltd. (TSE:4523; ADR:ESALY) is a research-based human
health care (hhc) company that discovers, develops and markets
products throughout the world. Eisai focuses its efforts in three
therapeutic areas: integrative neuroscience, including neurology
and psychiatric medicines; integrative oncology, which encompasses
oncotherapy and supportive-care treatments; and
vascular/immunological reaction. Through a global network of
research facilities, manufacturing sites and marketing
subsidiaries, Eisai actively participates in all aspects of the
worldwide healthcare system. For more information about Eisai Co.,
Ltd., please visit www.eisai.com.
Source: Eisai
Contact:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120
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