NUTLEY,
N.J., June 27, 2024 /PRNewswire/ -- Eisai
today announced results from a post-hoc analysis from the Phase 3
REFLECT trial, which looked at efficacy outcomes characterized by
depth of response in patients with unresectable hepatocellular
carcinoma (uHCC) treated with LENVIMA® (lenvatinib) as a
first-line systemic therapy. This analysis shows that median
overall survival (OS) in patients treated with LENVIMA who achieved
a near-complete response (near-CR) was similar to that of patients
who experienced a complete response (CR). These data are being
presented in a poster display session (#168P) at the 2024 European
Society for Medical Oncology (ESMO) Gastrointestinal Cancers
Congress, which is taking place in Munich from June 26–29.
Of the 478 patients randomly assigned to receive LENVIMA in the
REFLECT trial, 194 patients (41%) had an objective response, as
assessed by independent imaging review per mRECIST, and were
included in this analysis; the statistics of this post-hoc analysis
are descriptive in nature. Of the 194 patients who had an objective
response, 10 had a CR and 184 had a partial response ([PR]: 49 had
a near-CR with ≥75% TLR (target lesion reduction); 72 had a PR with
≥50% to <75% TLR; and 63 had a PR with ≥30% to <50% TLR).
In the analysis, OS was similar for patients with CR (25.4
months; 95% CI: 5.5–NE [not estimable]) and near-CR (23.4 months;
95% CI: 12.0–30.1), which were higher compared to patients with PR
with ≥50% to <75% TLR (19.8 months; 95% CI: 14.1–23.1) and PR
with ≥30% to <50% TLR (14.4 months; 95% CI: 13.1–19.1). OS rates
at 12 and 24 months, respectively, were:
- CR: 80.0% (95% CI: 40.9-94.6) and 60.0% (95% CI:
25.3-82.7);
- near-CR with ≥75% TLR: 63.2% (95% CI: 48.1-75) and 48.0% (95%
CI: 33.3-61.2);
- PR with ≥50% to <75% TLR: 70.8% (95% CI: 58.9-79.9) and
37.4% (95% CI: 25.7-49.0); and
- PR with ≥30% to <50% TLR: 67.2% (95% CI: 53.9-77.5) and
30.4% (95% CI: 19.3-42.3).
The median duration of response (DOR) was 20.3 months (95% CI:
4.7-NE) for patients with CR. Median DOR was similar among patients
with near-CR and PR with ≥50% to <75% TLR, 7.7 months (95% CI:
6.9-9.2) and 7.3 months (95% CI: 5.5-7.4), respectively; while
patients with PR with ≥30% to <50% TLR had a median DOR of 3.7
months (95% CI: 3.7-5.6). Of patients with near-CR, 10.2%
maintained their response for more than 18 months, and 8.3% of
patients with PR with ≥50% to <75% TLR maintained their response
for more than 18 months.
"This study, the first to examine near-complete response in this
disease, demonstrates that LENVIMA may help these patients live
nearly as long as those with a complete response, reinforcing the
important role of LENVIMA as a first-line treatment for
unresectable hepatocellular carcinoma," said Dr. Takashi Owa, Chief Scientific Officer, Senior
Vice President, Eisai Co., Ltd. "These data add to the existing
body of knowledge on the activity of LENVIMA in first-line
unresectable HCC, which may aid healthcare providers in identifying
the most appropriate treatment options for their patients and we're
grateful to our investigators for their commitment to this
goal."
Improved progression-free survival (PFS) was observed in
patients with CR (22.1 months; 95% CI: 6.4-NE) compared to patients
with any PR [near-CR: 10.5 months (95% CI: 9.1–11.1); PR with ≥50%
to <75% TLR: 9.2 months (95% CI: 7.4–11.1); PR with ≥30% to
<50% TLR: 7.4 months (95% CI: 5.5–9.2)].
LENVIMA was approved by the U.S. Food and Drug Administration
(FDA) in August 2018 for the treatment of patients with
unresectable hepatocellular carcinoma (HCC) based on data from the
REFLECT trial.
About the REFLECT Trial (Study 304)
REFLECT was an international, multicenter, randomized,
open-label, non-inferiority Phase 3 study to compare the efficacy
and safety of LENVIMA versus sorafenib as a first-line systemic
treatment in patients with uHCC. Patients (n=954) at 183 trial
sites in 21 countries were randomized to receive LENVIMA 12 mg or 8
mg once a day depending on body weight (≥60 kg or <60 kg,
respectively) (n=478) or sorafenib 400 mg twice a day (n=476).
Treatment was continued until disease progression or unacceptable
toxicity. The primary endpoint of this study was overall survival.
LENVIMA showed non-inferior overall survival compared to sorafenib
(median OS for patients treated with LENVIMA was 13.6 months
compared to 12.3 months for sorafenib [HR: 0.92; 95% CI: 0.79 –
1.06]). Patients randomized to the LENVIMA arm did not have a
statistically significant improvement in OS compared to those in
the sorafenib arm. The secondary efficacy endpoints of this study
were progression-free survival (PFS), time to progression (TTP) and
objective response rate (ORR). Independent imaging review based on
mRECIST criteria confirmed superiority of LENVIMA to sorafenib on
these three tumor response assessments: median PFS with LENVIMA was
7.3 months vs. 3.6 months in the sorafenib arm (HR: 0.64; 95% CI:
0.55-0.75; p<0.001); median TTP with LENVIMA was 7.4 months vs.
3.7 months in the sorafenib arm (HR: 0.60; 95% CI: 0.51-0.71;
p<0.0001); ORR with LENVIMA was 41% vs. 12% in the sorafenib arm
(odds ratio: 5.01; 95% CI: 3.59-7.01; p<0.001).
The analysis presented at ESMO GI 2024 characterized OS, PFS and
duration of response outcomes among the 194 responders with a
complete or partial response to LENVIMA (as assessed by independent
imaging review per mRECIST), grouped based on their degree of tumor
size reduction at best overall response.
About Hepatocellular Carcinoma (HCC)
Hepatocellular
carcinoma is the most common type of primary liver cancer and in
the United States, liver cancer
incidence rates have tripled over the past four decades.
Hepatocellular carcinoma accounts for approximately 90% of primary
liver cancers. It is estimated that there were more than 866,000
new cases of liver cancer and more than 758,000 deaths from the
disease globally in 2022, making it the sixth most frequently
diagnosed cancer worldwide and one of the leading causes of cancer
deaths around the world. In the United
States, it is estimated there will be over 41,000 new cases
of liver cancer and approximately 30,000 deaths from this disease
in 2024. Risk factors for liver cancer include gender, ethnicity,
chronic viral hepatitis (Hep-B or Hep-C) infection, cirrhosis,
alcohol use and metabolic syndrome. Hepatocellular carcinoma, which
is often diagnosed at an advanced stage, has a five-year relative
survival rate of approximately 22% in the
United States.
About LENVIMA® (lenvatinib)
Capsules
LENVIMA is indicated:
- For the treatment of adult patients with locally recurrent or
metastatic, progressive, radioactive iodine-refractory
differentiated thyroid cancer (DTC)
- In combination with pembrolizumab, for the first line treatment
of adult patients with advanced renal cell carcinoma (RCC)
- In combination with everolimus for the treatment of adult
patients with advanced renal cell carcinoma (RCC) following one
prior anti-angiogenic therapy
- For the first-line treatment of patients with unresectable
hepatocellular carcinoma (HCC)
- In combination with pembrolizumab, for the treatment of
patients with advanced endometrial carcinoma (EC) that is mismatch
repair proficient (pMMR), as determined by an FDA-approved test, or
not microsatellite instability-high (MSI-H), who have disease
progression following prior systemic therapy in any setting and are
not candidates for curative surgery or radiation.
LENVIMA, discovered and developed by Eisai, is a multiple
receptor tyrosine kinase inhibitor that inhibits the kinase
activities of vascular endothelial growth factor (VEGF) receptors
VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits
other kinases that have been implicated in pathogenic angiogenesis,
tumor growth, and cancer progression in addition to their normal
cellular functions, including fibroblast growth factor (FGF)
receptors FGFR1-4, the platelet derived growth factor receptor
alpha (PDGFRA), KIT, and RET. Lenvatinib also exhibited
antiproliferative activity in hepatocellular carcinoma cell lines
dependent on activated FGFR signaling with a concurrent inhibition
of FGF-receptor substrate 2 alpha (FRS2) phosphorylation. In
syngeneic mouse tumor models, the combination of lenvatinib with an
anti-PD-1 monoclonal antibody decreased tumor-associated
macrophages, increased activated cytotoxic T cells, and
demonstrated greater antitumor activity compared to either
treatment alone. The combination of LENVIMA and everolimus showed
increased antiangiogenic and antitumor activity as demonstrated by
decreased human endothelial cell proliferation, tube formation, and
VEGF signaling in vitro and tumor volume in mouse xenograft models
of human renal cell cancer greater than each drug alone.
Important Safety Information for LENVIMA
Warnings and Precautions
Hypertension. In DTC (differentiated thyroid cancer),
hypertension occurred in 73% of patients on LENVIMA (44% grade
3-4). In RCC (renal cell carcinoma), hypertension occurred in 42%
of patients on LENVIMA + everolimus (13% grade 3). Systolic blood
pressure ≥160 mmHg occurred in 29% of patients, and 21% had
diastolic blood pressure ≥100 mmHg. In HCC (hepatocellular
carcinoma), hypertension occurred in 45% of LENVIMA-treated
patients (24% grade 3). Grade 4 hypertension was not reported in
HCC.
Serious complications of poorly controlled hypertension have
been reported. Control blood pressure prior to initiation. Monitor
blood pressure after 1 week, then every 2 weeks for the first 2
months, and then at least monthly thereafter during treatment.
Withhold and resume at reduced dose when hypertension is controlled
or permanently discontinue based on severity.
Cardiac Dysfunction. Serious and fatal cardiac
dysfunction can occur with LENVIMA. Across clinical trials in 799
patients with DTC, RCC, and HCC, grade 3 or higher cardiac
dysfunction occurred in 3% of LENVIMA-treated patients. Monitor for
clinical symptoms or signs of cardiac dysfunction. Withhold and
resume at reduced dose upon recovery or permanently discontinue
based on severity.
Arterial Thromboembolic Events. Among patients receiving
LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of
any severity occurred in 2% of patients in RCC and HCC and 5% in
DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3%
across all clinical trials.
Among patients receiving LENVIMA with pembrolizumab, arterial
thrombotic events of any severity occurred in 5% of patients in
CLEAR, including myocardial infarction (3.4%) and cerebrovascular
accident (2.3%).
Permanently discontinue following an arterial thrombotic event.
The safety of resuming after an arterial thromboembolic event has
not been established, and LENVIMA has not been studied in patients
who have had an arterial thromboembolic event within the previous 6
months.
Hepatotoxicity. Across clinical studies enrolling 1327
LENVIMA-treated patients with malignancies other than HCC, serious
hepatic adverse reactions occurred in 1.4% of patients. Fatal
events, including hepatic failure, acute hepatitis, and hepatorenal
syndrome, occurred in 0.5% of patients. In HCC, hepatic
encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade
3-5). Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated
patients; 2% of patients discontinued LENVIMA due to hepatic
encephalopathy, and 1% discontinued due to hepatic failure.
Monitor liver function prior to initiation, then every 2 weeks
for the first 2 months, and at least monthly thereafter during
treatment. Monitor patients with HCC closely for signs of hepatic
failure, including hepatic encephalopathy. Withhold and resume at
reduced dose upon recovery or permanently discontinue based on
severity.
Renal Failure or Impairment. Serious including fatal
renal failure or impairment can occur with LENVIMA. Renal
impairment was reported in 14% and 7% of LENVIMA-treated patients
in DTC and HCC, respectively. Grade 3-5 renal failure or impairment
occurred in 3% of patients with DTC and 2% of patients with HCC,
including 1 fatal event in each study. In RCC, renal impairment or
renal failure was reported in 18% of LENVIMA + everolimus–treated
patients (10% grade 3).
Initiate prompt management of diarrhea or
dehydration/hypovolemia. Withhold and resume at reduced dose upon
recovery or permanently discontinue for renal failure or impairment
based on severity.
Proteinuria. In DTC and HCC, proteinuria was reported in
34% and 26% of LENVIMA-treated patients, respectively. Grade 3
proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In
RCC, proteinuria occurred in 31% of patients receiving LENVIMA +
everolimus (8% grade 3). Monitor for proteinuria prior to
initiation and periodically during treatment. If urine dipstick
proteinuria ≥2+ is detected, obtain a 24-hour urine protein.
Withhold and resume at reduced dose upon recovery or permanently
discontinue based on severity.
Diarrhea. Of the 737 LENVIMA-treated patients in DTC and
HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea
occurred in 81% of LENVIMA + everolimus–treated patients (19% grade
3). Diarrhea was the most frequent cause of dose
interruption/reduction, and diarrhea recurred despite dose
reduction. Promptly initiate management of diarrhea. Withhold and
resume at reduced dose upon recovery or permanently discontinue
based on severity.
Fistula Formation and Gastrointestinal Perforation. Of
the 799 patients treated with LENVIMA or LENVIMA + everolimus in
DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred
in 2%. Permanently discontinue in patients who develop
gastrointestinal perforation of any severity or grade 3-4
fistula.
QT Interval Prolongation. In DTC, QT/QTc interval
prolongation occurred in 9% of LENVIMA-treated patients and QT
interval prolongation of >500 ms occurred in 2%. In RCC, QTc
interval increases of >60 ms occurred in 11% of patients
receiving LENVIMA + everolimus and QTc interval >500 ms occurred
in 6%. In HCC, QTc interval increases of >60 ms occurred in 8%
of LENVIMA-treated patients and QTc interval >500 ms occurred in
2%.
Monitor and correct electrolyte abnormalities at baseline and
periodically during treatment. Monitor electrocardiograms in
patients with congenital long QT syndrome, congestive heart
failure, bradyarrhythmias, or those who are taking drugs known to
prolong the QT interval, including Class Ia and III
antiarrhythmics. Withhold and resume at reduced dose upon recovery
based on severity.
Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in
9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia
improved or resolved following calcium supplementation with or
without dose interruption or dose reduction. In RCC, grade 3-4
hypocalcemia occurred in 6% of LENVIMA + everolimus–treated
patients. In HCC, grade 3 hypocalcemia occurred in 0.8% of
LENVIMA-treated patients. Monitor blood calcium levels at least
monthly and replace calcium as necessary during treatment. Withhold
and resume at reduced dose upon recovery or permanently discontinue
depending on severity.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS).
Across clinical studies of 1823 patients who received LENVIMA as a
single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with
MRI. Withhold and resume at reduced dose upon recovery or
permanently discontinue depending on severity and persistence of
neurologic symptoms.
Hemorrhagic Events. Serious including fatal hemorrhagic
events can occur with LENVIMA. In DTC, RCC, and HCC clinical
trials, hemorrhagic events, of any grade, occurred in 29% of the
799 patients treated with LENVIMA as a single agent or in
combination with everolimus. The most frequently reported
hemorrhagic events (all grades and occurring in at least 5% of
patients) were epistaxis and hematuria. In DTC, grade 3-5
hemorrhage occurred in 2% of LENVIMA-treated patients, including 1
fatal intracranial hemorrhage among 16 patients who received
LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5
hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients,
including 1 fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage
occurred in 5% of LENVIMA-treated patients, including 7 fatal
hemorrhagic events. Serious tumor-related bleeds, including fatal
hemorrhagic events, occurred in LENVIMA-treated patients in
clinical trials and in the postmarketing setting. In postmarketing
surveillance, serious and fatal carotid artery hemorrhages were
seen more frequently in patients with anaplastic thyroid carcinoma
(ATC) than other tumors. Safety and effectiveness of LENVIMA in
patients with ATC have not been demonstrated in clinical
trials.
Consider the risk of severe or fatal hemorrhage associated with
tumor invasion or infiltration of major blood vessels (eg, carotid
artery). Withhold and resume at reduced dose upon recovery or
permanently discontinue based on severity.
Impairment of Thyroid Stimulating Hormone Suppression/Thyroid
Dysfunction. LENVIMA impairs exogenous thyroid suppression. In
DTC, 88% of patients had baseline thyroid stimulating hormone (TSH)
level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation
of TSH level >0.5 mU/L was observed post baseline in 57% of
LENVIMA-treated patients. In RCC and HCC, grade 1 or 2
hypothyroidism occurred in 24% of LENVIMA + everolimus–treated
patients and 21% of LENVIMA-treated patients, respectively. In
patients with normal or low TSH at baseline, elevation of TSH was
observed post baseline in 70% of LENVIMA-treated patients in HCC
and 60% of LENVIMA + everolimus–treated patients in RCC.
Monitor thyroid function prior to initiation and at least
monthly during treatment. Treat hypothyroidism according to
standard medical practice.
Impaired Wound Healing. Impaired wound healing has been
reported in patients who received LENVIMA. Withhold LENVIMA for at
least 1 week prior to elective surgery. Do not administer for at
least 2 weeks following major surgery and until adequate wound
healing. The safety of resumption of LENVIMA after resolution of
wound healing complications has not been established.
Osteonecrosis of the Jaw (ONJ). ONJ has been reported in
patients receiving LENVIMA. Concomitant exposure to other risk
factors, such as bisphosphonates, denosumab, dental disease, or
invasive dental procedures, may increase the risk of ONJ.
Perform an oral examination prior to treatment with LENVIMA and
periodically during LENVIMA treatment. Advise patients regarding
good oral hygiene practices and to consider having preventive
dentistry performed prior to treatment with LENVIMA and throughout
treatment with LENVIMA.
Avoid invasive dental procedures, if possible, while on LENVIMA
treatment, particularly in patients at higher risk. Withhold
LENVIMA for at least 1 week prior to scheduled dental surgery or
invasive dental procedures, if possible. For patients requiring
invasive dental procedures, discontinuation of bisphosphonate
treatment may reduce the risk of ONJ.
Withhold LENVIMA if ONJ develops and restart based on clinical
judgement of adequate resolution.
Embryo-Fetal Toxicity. Based on its mechanism of
action and data from animal reproduction studies, LENVIMA can cause
fetal harm when administered to pregnant women. In animal
reproduction studies, oral administration of lenvatinib during
organogenesis at doses below the recommended clinical doses
resulted in embryotoxicity, fetotoxicity, and teratogenicity in
rats and rabbits. Advise pregnant women of the potential risk to a
fetus and advise females of reproductive potential to use effective
contraception during treatment with LENVIMA and for 30 days after
the last dose.
Adverse Reactions
In DTC, the most common adverse
reactions (≥30%) observed in LENVIMA-treated patients were
hypertension (73%), fatigue (67%), diarrhea (67%),
arthralgia/myalgia (62%), decreased appetite (54%), decreased
weight (51%), nausea (47%), stomatitis (41%), headache (38%),
vomiting (36%), proteinuria (34%), palmar-plantar
erythrodysesthesia syndrome (32%), abdominal pain (31%), and
dysphonia (31%). The most common serious adverse reactions (≥2%)
were pneumonia (4%), hypertension (3%), and dehydration (3%).
Adverse reactions led to dose reductions in 68% of LENVIMA-treated
patients; 18% discontinued LENVIMA. The most common adverse
reactions (≥10%) resulting in dose reductions were hypertension
(13%), proteinuria (11%), decreased appetite (10%), and diarrhea
(10%); the most common adverse reactions (≥1%) resulting in
discontinuation of LENVIMA were hypertension (1%) and asthenia
(1%).
In RCC, the most common adverse reactions (≥20%) observed in
LENVIMA + pembrolizumab-treated patients were fatigue (63%),
diarrhea (62%), musculoskeletal pain (58%), hypothyroidism (57%),
hypertension (56%), stomatitis (43%), decreased appetite (41%),
rash (37%), nausea (36%), decreased weight (30%), dysphonia (30%),
proteinuria (30%), palmar-plantar erythrodysesthesia syndrome
(29%), abdominal pain (27%), hemorrhagic events (27%), vomiting
(26%), constipation (25%), hepatotoxicity (25%), headache (23%),
and acute kidney injury (21%). The most common serious adverse
reactions (≥2%) were hemorrhagic events (5%), diarrhea (4%),
hypertension (3%), myocardial infarction (3%), pneumonitis (3%),
vomiting (3%), acute kidney injury (2%), adrenal insufficiency
(2%), dyspnea (2%), and pneumonia (2%). Fatal adverse reactions
occurred in 4.3% of patients receiving LENVIMA in combination with
pembrolizumab, including cardio-respiratory arrest (0.9%), sepsis
(0.9%), and one case (0.3%) each of arrhythmia, autoimmune
hepatitis, dyspnea, hypertensive crisis, increased blood
creatinine, multiple organ dysfunction syndrome, myasthenic
syndrome, myocarditis, nephritis, pneumonitis, ruptured aneurysm
and subarachnoid hemorrhage. Serious adverse reactions occurred in
51% of patients receiving LENVIMA and pembrolizumab. Serious
adverse reactions in ≥2% of patients were hemorrhagic events (5%),
diarrhea (4%), hypertension (3%), myocardial infarction (3%),
pneumonitis (3%), vomiting (3%), acute kidney injury (2%), adrenal
insufficiency (2%), dyspnea (2%), and pneumonia (2%). Permanent
discontinuation of LENVIMA, pembrolizumab, or both due to an
adverse reaction occurred in 37% of patients; 26% LENVIMA only, 29%
pembrolizumab only, and 13% both drugs. The most common adverse
reactions (≥2%) leading to permanent discontinuation of LENVIMA,
pembrolizumab, or both were pneumonitis (3%), myocardial infarction
(3%), hepatotoxicity (3%), acute kidney injury (3%), rash (3%), and
diarrhea (2%). Dose interruptions of LENVIMA, pembrolizumab, or
both due to an adverse reaction occurred in 78% of patients
receiving LENVIMA in combination with pembrolizumab. LENVIMA was
interrupted in 73% of patients and both drugs were interrupted in
39% of patients. LENVIMA was dose reduced in 69% of patients. The
most common adverse reactions (≥5%) resulting in dose reduction or
interruption of LENVIMA were diarrhea (26%), fatigue (18%),
hypertension (17%), proteinuria (13%), decreased appetite (12%),
palmar-plantar erythrodysesthesia (11%), nausea (9%), stomatitis
(9%), musculoskeletal pain (8%), rash (8%), increased lipase (7%),
abdominal pain (6%), and vomiting (6%), increased ALT (5%), and
increased amylase (5%).
In RCC, the most common adverse reactions (≥30%) observed in
LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue
(73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting
(48%), nausea (45%), stomatitis (44%), hypertension (42%),
peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea
(35%), rash (35%), decreased weight (34%), hemorrhagic events
(32%), and proteinuria (31%). The most common serious adverse
reactions (≥5%) were renal failure (11%), dehydration (10%), anemia
(6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and
dyspnea (5%). Adverse reactions led to dose reductions or
interruption in 89% of patients. The most common adverse reactions
(≥5%) resulting in dose reductions were diarrhea (21%), fatigue
(8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and
proteinuria (5%). Treatment discontinuation due to an adverse
reaction occurred in 29% of patients.
In HCC, the most common adverse reactions (≥20%) observed in
LENVIMA-treated patients were hypertension (45%), fatigue (44%),
diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%),
decreased weight (31%), abdominal pain (30%), palmar-plantar
erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia
(24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea
(20%). The most common serious adverse reactions (≥2%) were hepatic
encephalopathy (5%), hepatic failure (3%), ascites (3%), and
decreased appetite (2%). Adverse reactions led to dose reductions
or interruption in 62% of patients. The most common adverse
reactions (≥5%) resulting in dose reductions were fatigue (9%),
decreased appetite (8%), diarrhea (8%), proteinuria (7%),
hypertension (6%), and palmar-plantar erythrodysesthesia syndrome
(5%). Treatment discontinuation due to an adverse reaction occurred
in 20% of patients. The most common adverse reactions (≥1%)
resulting in discontinuation of LENVIMA were fatigue (1%), hepatic
encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure
(1%).
In EC, the most common adverse reactions (≥20%) observed in
LENVIMA and pembrolizumab–treated patients were hypothyroidism
(67%), hypertension (67%), fatigue (58%), diarrhea (55%),
musculoskeletal disorders (53%), nausea (49%), decreased appetite
(44%), vomiting (37%), stomatitis (35%), decreased weight (34%),
abdominal pain (34%), urinary tract infection (31%), proteinuria
(29%), constipation (27%), headache (26%), hemorrhagic events
(25%), palmar‐plantar erythrodysesthesia (23%), dysphonia (22%),
and rash (20%). Fatal adverse reactions occurred in 4.7% of those
treated with LENVIMA and pembrolizumab, including 2 cases of
pneumonia, and 1 case of the following: acute kidney injury, acute
myocardial infarction, colitis, decreased appetite, intestinal
perforation, lower gastrointestinal hemorrhage, malignant
gastrointestinal obstruction, multiple organ dysfunction syndrome,
myelodysplastic syndrome, pulmonary embolism, and right ventricular
dysfunction. Serious adverse reactions occurred in 50% of patients
receiving LENVIMA and pembrolizumab. Serious adverse reactions with
frequency ≥3% were hypertension (4.4%), and urinary tract infection
(3.2%). Discontinuation of LENVIMA due to an adverse reaction
occurred in 26% of patients. The most common (≥1%) adverse
reactions leading to discontinuation of LENVIMA were hypertension
(2%), asthenia (1.8%), diarrhea (1.2%), decreased appetite (1.2%),
proteinuria (1.2%), and vomiting (1.2%). Dose reductions of LENVIMA
due to adverse reactions occurred in 67% of patients. The most
common (≥5%) adverse reactions resulting in dose reduction of
LENVIMA were hypertension (18%), diarrhea (11%), palmar-plantar
erythrodysesthesia syndrome (9%), proteinuria (7%), fatigue (7%),
decreased appetite (6%), asthenia (5%), and weight decreased (5%).
Dose interruptions of LENVIMA due to an adverse reaction occurred
in 58% of these patients. The most common (≥2%) adverse reactions
leading to interruption of LENVIMA were hypertension (11%),
diarrhea (11%), proteinuria (6%), decreased appetite (5%), vomiting
(5%), increased alanine aminotransferase (3.5%), fatigue (3.5%),
nausea (3.5%), abdominal pain (2.9%), weight decreased (2.6%),
urinary tract infection (2.6%), increased aspartate
aminotransferase (2.3%), asthenia (2.3%), and palmar-plantar
erythrodysesthesia (2%).
Use in Specific Populations
Because of the potential
for serious adverse reactions in breastfed children, advise women
to discontinue breastfeeding during treatment and for 1 week after
the last dose. LENVIMA may impair fertility in males and females of
reproductive potential.
No dose adjustment is recommended for patients with mild (CLcr
60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment.
LENVIMA concentrations may increase in patients with DTC, RCC, or
EC and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose
for patients with DTC, RCC, or EC and severe renal impairment.
There is no recommended dose for patients with HCC and severe renal
impairment. LENVIMA has not been studied in patients with end-stage
renal disease.
No dose adjustment is recommended for patients with HCC and mild
hepatic impairment (Child-Pugh A). There is no recommended dose for
patients with HCC with moderate (Child-Pugh B) or severe
(Child-Pugh C) hepatic impairment. No dose adjustment is
recommended for patients with DTC, RCC, or EC and mild or moderate
hepatic impairment. LENVIMA concentrations may increase in patients
with DTC, RCC, or EC and severe hepatic impairment. Reduce the dose
for patients with DTC, RCC, or EC and severe hepatic
impairment.
LENVIMA (lenvatinib) is available as 10 mg and 4 mg
capsules.
Please see Prescribing Information for LENVIMA (lenvatinib) at
http://www.lenvima.com/pdfs/prescribing-information.pdf
About Eisai
Eisai's Corporate Concept is "to
give first thought to patients and people in the daily living
domain, and to increase the benefits that health care provides."
Under this Concept [also known as our human health
care (hhc) Concept], we aim to
effectively achieve social good in the form of relieving anxiety
over health and reducing health disparities. With a global network
of R&D facilities, manufacturing sites and marketing
subsidiaries, we strive to create and deliver innovative products
to target diseases with high unmet medical needs, with a particular
focus in our strategic areas of Neurology and Oncology.
In addition, our continued commitment to the elimination of
neglected tropical diseases (NTDs), which is a target (3.3) of the
United Nations Sustainable Development Goals (SDGs), is
demonstrated by our work on various activities together with global
partners.
For more information about Eisai, please visit
www.eisai.com (for global headquarters: Eisai Co., Ltd.),
us.eisai.com (for U.S. headquarters: Eisai Inc.) or
www.eisai.eu (for Europe,
Middle East, Africa, Russia, Australia, and New
Zealand headquarters: Eisai Europe Ltd.), and connect with
us on Twitter (U.S. and global) and LinkedIn (for
U.S. and EMEA).
LENVIMA® is a registered trademark used by Eisai Inc.
under license from Eisai R&D Management Co., Ltd.
©2024 Eisai Inc. All Rights Reserved.
View original content to download
multimedia:https://www.prnewswire.com/news-releases/new-post-hoc-analysis-from-phase-3-reflect-trial-presented-at-esmo-gi-2024-explores-efficacy-outcomes-with-lenvima-lenvatinib-based-on-depth-of-tumor-response-in-unresectable-hepatocellular-carcinoma-302184539.html
SOURCE Eisai Inc.