Eisai Presents Results of Phase Iii Clinical Study of Lenvima (Lenvatinib) in Unresectable Hepatocellular Carcinoma at 11th...
2017年9月19日 - 10:01AM
JCN Newswire (英)
Eisai Co., Ltd. has announced that the results of a
subpopulation analysis of patients with hepatitis B virus (HBV)
coinfection in a Phase III trial (REFLECT / Study 304) of its
in-house discovered and developed anticancer agent lenvatinib
mesylate (product names: Lenvima / Kisplyx, "lenvatinib") versus
sorafenib as a first-line treatment for unresectable HCC were
presented for the first time during the 11th Annual Conference of
the International Liver Cancer Association (ILCA) held in Seoul,
South Korea.
In the total population analysis of this study, the treatment
effect of lenvatinib for all patients on the primary endpoint of
Overall Survival (OS) was demonstrated by statistical confirmation
of non-inferiority to sorafenib. 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 analysis
results presented at ILCA indicate that in comparison to the total
population, lenvatinib demonstrated a lower hazard ratio for OS,
FPS, and TTP, and a higher odds ratio for ORR in the subpopulation
of patients with HBV (See table below). HBV is considered to be a
negative predictor of tumor response to existing drug therapies, so
lenvatinib, which demonstrated a therapeutic effect in patients
with HBV, is expected to be a new treatment option for patients
with HCC.
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Additionally, safety results were similar in patients with HBV and
the total population in the lenvatinib arm. The five most common
treatment-emergent adverse events in patients with HBV in the
lenvatinib arm were hypertension, diarrhea, decreased weight,
fatigue and decreased appetite.
Liver cancer is the second leading cause of cancer related deaths
and is estimated to be responsible for 750,000 deaths per year
globally. Additionally, 780,000 cases are newly diagnosed each
year, about 80% of which occur in Asian regions. HCC accounts for
85% to 90% of primary liver cancer cases. Treatment options for
unresectable HCC are limited and the prognosis is very poor, making
this an area of high unmet medical need. Following submissions in
Japan (June 2017), the United States, and Europe (July 2017), Eisai
will submit a regulatory application for lenvatinib in HCC in China
within the latter half of fiscal 2017.
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 (product names: Lenvima, Kisplyx,
"lenvatinib")
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, and in
Europe. 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 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 REFLECT Study (Study 304)(1)
The REFLECT study (A Multicenter, Randomized, Open-Label, Phase 3
Trial to Compare the Efficacy and Safety of Lenvatinib (E7080)
Versus Sorafenib in First-Line Treatment of Subjects With
Unresectable Hepatocellular Carcinoma) is a multicenter,
open-label, randomized, global Phase III study comparing the
efficacy and safety of lenvatinib versus sorafenib. 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
Overall Survival (OS), with the goal of demonstrating
non-inferiority. Other factors including Progression Free Survival
(PFS), Time To Progression (TTP), Objective Response Rate (ORR) and
Quality of Life (QOL) were assessed as secondary endpoints.
According to the results of the study, lenvatinib met the
statistical criteria for non-inferiority in the primary endpoint of
OS compared to sorafenib (lenvatinib 13.6 months versus sorafenib
12.3 months in median, Hazard Ratio [HR] 0.92, 95% Confidence
Interval (CI) = 0.79-1.06) Additionally, lenvatinib showed
statistically significant improvements in the three secondary
efficacy endpoints, doubling sorafenib's median values and ratios:
PFS (lenvatinib 7.4 months versus sorafenib 3.7 months in median,
HR 0.66, 95% CI = 0.57-0.77, P<0.00001), TTP (lenvatinib 8.9
months versus sorafenib 3.7 months in median, HR 0.63, 95% CI =
0.53-0.73, P<0.00001) and ORR (lenvatinib 24% versus sorafenib
9%, P<0.00001). 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.
(1) Cheng A 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) 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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