Eisai Presents Results of Analysis of Phase III Trial of Lenvima (Lenvatinib)
2018年1月22日 - 10:51AM
JCN Newswire (英)
Eisai Co., Ltd. announced today that the results of an analysis
of a Phase III trial (REFLECT study / Study 304)(1) of its in-house
discovered and developed anticancer agent lenvatinib mesylate
versus sorafenib as first-line treatment for unresectable
hepatocellular carcinoma based on independent imaging review were
presented(2) during the American Society of Clinical Oncology
Gastrointestinal Cancers Symposium (ASCO-GI) 2018, in San
Francisco, the United States.
The presentation reported on an exploratory analysis of the
secondary endpoints of Progression Free Survival (PFS), Time To
Progression (TTP), and Objective Response Rate (ORR) in the REFLECT
study based on blinded independent imaging review (IIR).
The IIR based on both RECIST (Response Evaluation Criteria in Solid
Tumors) 1.1, which uses the traditional assessment of the effect on
change in tumor diameter, and modified RECIST (mRECIST), which
takes into account areas of tumor necrosis in addition to the
RECIST 1.1 criteria, confirmed the investigators' findings of
extensions in PFS and TTP as well as an increase in ORR compared to
sorafenib (refer to the tables below) based on lenvatinib's
superior reduction in tumor size. The results of the blinded IIR of
the REFLECT study support the imaging findings of the clinical
trial investigators.
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.
Liver cancer is the second leading cause of cancer related deaths
and is estimated to be responsible for 750,000 deaths per year
globally.3 Additionally, 780,000 cases are newly diagnosed each
year, about 80% of which occur in Asian regions, including Japan
and China.(3)
Hepatocellular carcinoma accounts for 85% to 90% of primary liver
cancer cases. Early stage hepatocellular carcinoma is treatable by
a wide variety of means, including surgery, radiofrequency
ablation, ethanol injection, and chemoembolization therapy, but
treatment opinions for unresectable hepatocellular carcinoma are
limited and the prognosis is very poor, meaning that this is an
area of high unmet medical need.
Eisai submitted applications for an additional indication 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
generating scientific evidence aimed at maximizing the value of
lenvatinib 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 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 in the United States, Europe, and
other countries, as a treatment for renal cell carcinoma
(second-line). In Europe, lenvatinib was launched under the brand
name Kisplyx for this indication.
A Phase III study (Study 307) of lenvatinib in separate
combinations with everolimus and pembrolizumab in renal cell
carcinoma (first-line) is underway. A Phase Ib/II study to
investigate the agent in combination with pembrolizumab in select
solid tumors (non-small cell lung cancer, renal cell carcinoma,
endometrial cancer, urothelial cancer, head and neck cancer, and
melanoma) is underway. Additionally, a Phase Ib study of the agent
in hepatocellular carcinoma is also underway.
About Study 304
Study 304 is a multicenter, randomized, open-label, 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 for patients with unresectable
hepatocellular carcinoma. In the study, 954 patients were
randomized in a 1:1 ratio to receive lenvatinib 12 mg or 8 mg 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 Overall Survival (OS), with the goal of demonstrating
non-inferiority. Other factors including PSF, 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 side-effect profile of
lenvatinib.
About the Independent Imaging Review and the Clinical Trial
Investigators' Review
In order to preserve the uniformity of imaging assessment, an
independent imaging review is conducted by a testing organization
(central testing laboratory) which is independent of the medical
organizations conducting the clinical trial. The clinical trial
investigators' review is a review by the physician in charge of the
clinical trial at each medical organization according to specific
criteria (such as RECIST).
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 Progression Free Survival (PFS), Time to Progression (TTP)
and Objective Response Rate (ORR)
PFS is the time from the date of randomization to the date of
disease progression, or date of death from any cause, whichever
occurs first. TTP is the time until the date of disease
progression, and is different to PFS in that it does not consider
death from any cause. ORR is the combined proportion of patients
whose tumor was eliminated (complete response) and whose tumor was
reduced by over 30% in size (partial response).
(1) A. Cheng et al. "Phase 3 trial of lenvatinib vs sorafenib in
first-line treatment of patients with unresectable hepatocellular
carcinoma", the 53rd Annual Meeting of the American Society of
Clinical Oncology (ASCO), (June 2017), Abstract No: 4001
(2) Lencioni R, et al. "Independent imaging review (IIR) results in
a phase 3 trial of lenvatinib (LEN) versus sorafenib (SOR) in
first-line treatment of patients (pts) with unresectable
hepatocellular carcinoma (uHCC)," ASCO-GI 2018, Abstract #345
(3) 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.
+81-3-3817-5120
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