Eisai Data at ASCO 2021 Highlight Breadth of Oncology Portfolio Across Various Tumor Types
Eisai to present more than 25 abstracts including investigational data on oncology pipeline and products
Oral presentations include two trials from the LEAP (Lenvatinib And Pembrolizumab) clinical program evaluating the combination in patients with advanced renal cell carcinoma and advanced melanoma

WOODCLIFF LAKE, N.J., May 17, 2021 /PRNewswire/ -- Eisai Inc. announced today the presentation of more than 25 abstracts across various types of cancer from its oncology portfolio during the virtual scientific program of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting from June 4 to 8. Notable data from ongoing LEAP clinical trials evaluating investigational uses of the KEYTRUDA® (pembrolizumab) plus LENVIMA® (lenvatinib) combination will be presented, including two oral presentations: one on updated Phase 2 data from the LEAP-004 trial evaluating lenvatinib plus pembrolizumab in advanced melanoma following prior PD-(L)1 therapy (NCT03776136; Abstract #9504) and the other on health-related quality of life (HRQoL) data from the pivotal Phase 3 CLEAR (KEYNOTE-581/Study 307) trial evaluating lenvatinib plus pembrolizumab or everolimus versus sunitinib in the first-line treatment of advanced renal cell carcinoma (NCT02811861; Abstract #4502).

Other data from the CLEAR study include a poster on a post hoc analysis of the effects of subsequent systemic therapy on survival outcomes in the lenvatinib plus everolimus and sunitinib arms (Abstract #4562), and a poster on the depth of response and efficacy in select subgroups in the lenvatinib plus pembrolizumab and sunitinib arms (Abstract #4560).

Key analyses on the lenvatinib plus pembrolizumab combination include a poster on the primary analysis of the health-related quality of life (HRQoL) endpoint from the pivotal Phase 3 KEYNOTE-775/Study 309 trial in patients with advanced endometrial cancer (NCT03517449; Abstract #5570) and a poster featuring first-ever biomarker data on the investigational lenvatinib plus pembrolizumab combination in unresectable hepatocellular carcinoma (HCC) (NCT03006926; Abstract #4084).

Additional lenvatinib data include an analysis on the impact of bodyweight-based starting doses of lenvatinib in patients with unresectable HCC (Abstract #e16119) and a comparative cost-effectiveness analysis evaluating lenvatinib versus other first-line therapies for patients with unresectable HCC in Canada (Abstract #4098).

In addition, posters featuring investigational data from three cohorts of the Phase 2 LEAP-005 basket trial – biliary tract, gastric and colorectal – will also be presented (NCT03797326; Abstracts #4080, #4030, #3564).

Eisai will also present results from a Phase 1 trial of E7389-LF (a novel liposomal formulation of eribulin) in patients with advanced gastric cancer (Abstract #4025), as well as real-world effectiveness data of HALAVEN® (eribulin mesylate) injection in patients with metastatic breast cancer with visceral metastases in the U.S. (Abstract #e13058).

"We are proud to present data from across our oncology portfolio at ASCO 2021, sharing our unifying commitment to exploring the avenues available to us—through molecules as monotherapies and in combination, in multiple formulations and cancer types—to potentially address the unmet needs of cancer patients," said Dr. Takashi Owa, Vice President, Chief Medicine Creation Officer and Chief Discovery Officer, Oncology Business Group at Eisai. "Additionally, the diversity of the lenvatinib plus pembrolizumab data at ASCO demonstrates the robust progress of the LEAP clinical program, which is exploring the potential of this combination to deliver clinical benefits to patients with advanced, metastatic, difficult-to-treat cancers in a variety of tumor types."

In March 2018, Eisai and Merck (known as MSD outside the United States and Canada), through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA, both as monotherapy and in combination with Merck's anti-PD-1 therapy KEYTRUDA. To date, more than 20 trials have been initiated under the LEAP (LEnvatinib And Pembrolizumab) clinical program, which is evaluating the combination across 14 different tumor types. For more information on the LEAP program, please visit clinicaltrials.gov.

This release discusses investigational compounds and investigational uses for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational compounds or investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.

The list of Eisai abstracts is included below. All abstracts will be available on demand via ASCO's website on Wednesday, May 19 at 5:00 PM EDT.

Lenvatinib Combinations (Plus Pembrolizumab or Everolimus)

Cancer Type

Study/Trial

Abstract Title

Abstract Type & Details

Skin Cancer

LEAP-004

Lenvatinib (LEN) plus pembrolizumab (pembro) for patients (pts) with advanced melanoma and confirmed progression on a PD-1 or PD-L1 Inhibitor: Updated findings of LEAP-004

 

Virtual Oral Presentation

Abstract #9504

June 6, 2021

8:00 AM – 11:00 AM EDT

 

Ana M. Arance Fernandez, MD, PhD, Hospital Clínic de Barcelona

 

Genitourinary Cancer

CLEAR study (KEYNOTE-581/ Study 307)

Health–related quality–of–life (HRQoL) analysis from the phase 3 CLEAR trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) or everolimus (EVE) vs sunitinib (SUN) for patients (pts) with advanced renal cell carcinoma (aRCC)

 

Virtual Oral Presentation

Abstract #4502

June 7, 2021

8:00 AM – 11:00 AM EDT

 

Robert J. Motzer, MD, Memorial Sloan Kettering Cancer Center

 

CLEAR study (KEYNOTE-581/ Study 307)

Analysis of the CLEAR study in patients (pts) with advanced renal cell carcinoma (RCC): depth of response and efficacy for selected subgroups in the lenvatinib (LEN) + pembrolizumab (PEMBRO) and sunitinib (SUN) treatment arms

 

Poster Session

Abstract #4560

Available on June 4, 2021

9:00 AM EDT

 

Viktor Grunwald, MD, PhD, University-Hospital Essen 

 

CLEAR study (KEYNOTE-581/ Study 307)

Post hoc analysis of the CLEAR study in advanced renal cell carcinoma (RCC):

Effect of subsequent therapy on survival outcomes in the lenvatinib (LEN) +

everolimus (EVE) vs sunitinib (SUN) treatment arms

 

Poster Session

Abstract #4562

Available on June 4, 2021

9:00 AM EDT

 

Thomas E. Hutson, DO, PharmD, Texas Oncology-Baylor Charles A. Sammons Cancer Center

 

KEYNOTE-146/ Study 111

Lenvatinib (LEN) + pembrolizumab (PEMBRO) treatment in patients (pts) with metastatic clear cell renal cell carcinoma (RCC): Final results of a phase 1b/2 trial

 

Online Publication

Abstract #e16542

 

Chung-Han Lee, MD, PhD, Memorial Sloan Kettering Cancer Center

 

MK-3475-U03A

A phase 1b/2 umbrella study of investigational immune and targeted combination therapies as first-line therapy for patients with advanced renal cell carcinoma (RCC)

 

Poster Session

Abstract #TPS4594

Available on June 4, 2021

9:00 AM EDT

 

Elizabeth R. Plimack, MD, Temple Health Fox Chase Cancer Center

 

KEYNOTE-B61

KEYNOTE-B61: Open-label phase 2 study of pembrolizumab in combination with lenvatinib as first-line treatment for non-clear cell renal cell carcinoma (nccRCC)

 

Poster Session

Abstract #TPS4595

Available on June 4, 2021

9:00 AM EDT

 

Chung-Han Lee, MD, PhD, Memorial Sloan Kettering Cancer Center

 

Gastrointestinal Cancers

Study 116

Exploratory circulating biomarker analyses: lenvatinib + pembrolizumab (L + P) in a phase 1b trial in unresectable hepatocellular carcinoma (uHCC)

Poster Session

Abstract #4084

Available on June 4, 2021

9:00 AM EDT

 

Andrew X. Zhu, MD, PhD, Massachusetts General Hospital

 

LEAP-005

LEAP-005: A phase 2 multicohort study of lenvatinib plus pembrolizumab in patients with previously treated selected solid tumors—Results from the gastric cancer cohort

 

Poster Session

Abstract #4030 

Available on June 4, 2021

9:00 AM EDT

 

Hyun Cheol C. Chung, MD, Yonsei Song-Dang Institute for Cancer Research

 

LEAP-005

LEAP-005: A phase 2 multicohort study of lenvatinib plus pembrolizumab in patients with previously treated selected solid tumors—Results from the colorectal cancer cohort

 

Poster Session

Abstract #3564

Available on June 4, 2021

9:00 AM EDT

 

Carlos A. Gomez-Roca, MD, Institut Universitaire du Cancer de Toulouse

 

LEAP-005

Lenvatinib plus pembrolizumab for patients with previously treated biliary tract cancers in the multicohort phase 2 LEAP-005 study

 

Poster Session

Abstract #4080

Available on June 4, 2021

9:00 AM EDT

 

Luis Villanueva, MD, Huntsville Hospital's Heart Center and Heart Institute

 

Gynecologic Cancer

KEYNOTE-775/ Study 309

Health-related quality of life (HRQoL) in advanced endometrial cancer (aEC) patients (pts) treated with lenvatinib plus pembrolizumab or treatment of physician's choice (TPC)

 

Poster Session

Abstract #5570

Available on June 4, 2021

9:00 AM EDT

 

Domenica Lorusso, MD, PhD, National Cancer Institute of Milan

 

Systematic literature review

Systematic literature review of the real-world burden and use of chemotherapies for treatment of advanced or recurrent endometrial carcinoma

 

Online Publication

Abstract #e17571

 

Qi Zhao, MD,

Eisai Inc.

ECHO-USA RWD Study

Treatment patterns and outcomes among patients with microsatellite stable (MSS) advanced endometrial cancer in the United States: Endometrial Cancer Health Outcomes (ECHO) retrospective chart review Study

Poster Session

Abstract #5581

Available on June 4, 2021

9:00 AM EDT

 

 

Shelby Corman, PharmD, MS, BCPS, Pharmerit International

 

Lenvatinib

Cancer Type

Study/Trial

Abstract Title

Abstract Type & Details

Gastrointestinal Cancers

Health Economics

The cost effectiveness of lenvatinib versus atezolizumab and bevacizumab or sorafenib in patients with unresectable hepatocellular carcinoma (uHCC) in Canada

 

Poster Session

Abstract #4098

Available on June 4, 2021

9:00 AM EDT

 

David Trueman, MSc

Source Health Economics

 

Real-world data

Real-world effectiveness of lenvatinib monotherapy among previously treated unresectable hepatocellular carcinoma patients in United States clinical practices

Online Publication

Abstract #e16129

 

Amit G. Singal, MD,

UT Southwestern Medical Center

 

Study 202/304

Impact of bodyweight (BW)-based starting doses on safety and efficacy of lenvatinib (LEN) in patients (pts) with hepatocellular carcinoma (HCC)

 

Online Publication

Abstract #e16119

 

Takuji Okusaka, MD, PhD, National Cancer Center Hospital

 

Indirect treatment comparison

The comparative efficacy of atezolizumab and bevacizumab vs. lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC)

 

Online Publication

Abstract #e16151

 

David Trueman, MSc

Source Health Economics

 

PMS/504

A multicenter observational study of lenvatinib for unresectable hepatocellular carcinoma in Japan

Online Publication

Abstract #e16118

 

Masatoshi Kudo, MD, PhD Kindai University

 

Eribulin & Pipeline

Cancer Type

Study/Trial

Abstract Title

Abstract Type & Details

Breast Cancer

Real-world data

Real-world clinical effectiveness of eribulin in metastatic breast cancer patients with visceral metastases in the United States

 

Online Publication

Abstract #e13058

 

Sarah Schellhorn Mougalian, MD, Yale Cancer Center

 

Gastrointestinal Cancers

Study 114

Phase 1 study of the liposomal formulation of eribulin (E7389-LF): Results from the advanced gastric cancer expansion cohort

 

Poster Session

Abstract #4025

Available on June 4, 2021

9:00 AM EDT

 

Ken Yamaguchi, MD, PhD, Shizuoka Cancer Center

 

Study 101

Phase I study of H3B-6527 in hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)

Poster Session

Abstract #4090

Available on June 4, 2021

9:00 AM EDT

 

Teresa Macarulla, MD, Vall D'Hebron University Hospital

 

Breast cancer

Study 102

Phase 1b study of H3B-6545 in combination with palbociclib in women with metastatic estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative breast cancer

Online Publication

Abstract #e13025

 

Stephen R.D. Johnston, MD, PhD, The Royal Marsden NHS Foundation Trust

 

Study 101

Phase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer

Poster Discussion Session

Abstract #1018

Available on June 4, 2021

9:00 A.M. EDT

 

Erika P. Hamilton, MD,

Sarah Cannon Institution of Breast and Gynecologic Cancer Research Program

 

Bioavailability and Drug-Drug Interaction

Relative bioavailability of H3B-6545 tablets versus capsules and drug-drug interaction between H3B-6545 and pantoprazole

Online Publication

Abstract #e13022

 

Jianjun Alan Xiao, PhD,

Eisai

 

Hematologic Cancers

Cost analysis

Health care cost impact associated with adverse events (AEs) among treatments in third-line+ (3L+) relapsed/refractory follicular lymphoma (R/R FL)

Online Publication

Abstract #e18836

 

Sameh Gaballa, MD,

Moffitt Cancer Center Department of Malignant Hematology

 

Additional Research

Abstract Title

Abstract Type & Details

Impact of #ASCO Twitter impressions on the oncology community

Poster Session

Abstract #11039

Available on June 4, 2021

9:00 A.M. EDT

 

Gilberto Morgan, MD, Skåne University Hospital

 

Perspectives on under-representation of minority patients (pts) in clinical trials

Online Publication

Abstract #e18521

 

Taofeek Owonikoko, MD, PhD, Winship Cancer Institute

 

About LENVIMA® (lenvatinib) Capsules
LENVIMA is indicated:

  • For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC)
  • In combination with everolimus, for the treatment of 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 not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy, and are not candidates for curative surgery or radiation. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial

LENVIMA, discovered and developed by Eisai, is a 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, platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGD-receptor substrate 2α (FRS2α) phosphorylation. The combination of lenvatinib and everolimus showed increased anti-angiogenic and anti-tumor activity as demonstrated by decreases in human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and decreases in tumor volume in mouse xenograft models of human renal cell cancer greater than with either drug alone. In syngeneic mouse tumor models, lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.

Important Safety Information

Warnings and Precautions
Hypertension. In DTC, hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In RCC, 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, 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. 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 1,327 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 1,823 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 at least 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 (≥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 + pembrolizumab-treated patients were fatigue (65%), hypertension (65%), musculoskeletal pain (65%), diarrhea (64%), decreased appetite (52%), hypothyroidism (51%), nausea (48%), stomatitis (43%), vomiting (39%), decreased weight (36%), abdominal pain (33%), headache (33%), constipation (32%), urinary tract infection (31%), dysphonia (29%), hemorrhagic events (28%), hypomagnesemia (27%), palmar-plantar erythrodysesthesia (26%), dyspnea (24%), cough (21%) and rash (21%). Adverse reactions led to dose reduction or interruption in 88% of patients receiving LENVIMA. The most common adverse reactions (≥5%) resulting in dose reduction or interruption of LENVIMA were fatigue (32%), hypertension (26%), diarrhea (18%), nausea (13%), palmar-plantar erythrodysesthesia (13%), vomiting (13%), decreased appetite (12%), musculoskeletal pain (11%), stomatitis (9%), abdominal pain (7%), hemorrhages (7%), renal impairment (6%), decreased weight (6%), rash (5%), headache (5%), increased lipase (5%) and proteinuria (5%). Fatal adverse reactions occurred in 3% of patients receiving LENVIMA + pembrolizumab, including gastrointestinal perforation, RPLS with intraventricular hemorrhage, and intracranial hemorrhage. Serious adverse reactions occurred in 52% of patients receiving LENVIMA + pembrolizumab. Serious adverse reactions in ≥3% of patients were hypertension (9%), abdominal pain (6%), musculoskeletal pain (5%), hemorrhage (4%), fatigue (4%), nausea (4%), confusional state (4%), pleural effusion (4%), adrenal insufficiency (3%), colitis (3%), dyspnea (3%), and pyrexia (3%). Permanent discontinuation due to adverse reaction (Grade 1-4) occurred in 21% of patients who received LENVIMA + pembrolizumab. The most common adverse reactions (>2%) resulting in discontinuation of LENVIMA were gastrointestinal perforation or fistula (2%), muscular weakness (2%), and pancreatitis (2%).

Use in Specific Populations
Because of the potential for serious adverse reactions in breastfed infants, advise women to discontinue breastfeeding during treatment and for at least 1 week after 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 HALAVEN® (eribulin mesylate) Injection
HALAVEN (eribulin mesylate) injection (0.5 mg/mL) is indicated for the treatment of patients with metastatic breast cancer (mBC) who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

Discovered and developed by Eisai, eribulin is a synthetic analog of halichondrin B, a natural product that was isolated from the marine sponge Halichondria okadai. First in the halichondrin class, eribulin is a microtubule dynamics inhibitor. Eribulin is believed to work primarily via a tubulin-based mechanism that causes prolonged and irreversible mitotic blockage, ultimately leading to apoptotic cell death. Additionally, in preclinical studies of human breast cancer, eribulin demonstrated complex effects on the tumor biology of surviving cancer cells, including increases in vascular perfusion resulting in reduced tumor hypoxia, and changes in the expression of genes in tumor specimens associated with a change in phenotype, promoting the epithelial phenotype, opposing the mesenchymal phenotype. Eribulin has also been shown to decrease the migration and invasiveness of human breast cancer cells.

Important Safety Information

Warnings and Precautions

Neutropenia: Severe neutropenia (ANC <500/mm3) lasting >1 week occurred in 12% of patients with mBC. Febrile neutropenia occurred in 5% of patients with mBC and 2 patients (0.4%) died from complications. Patients with mBC with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels. Monitor complete blood cell counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting >7 days.

Peripheral Neuropathy: Grade 3 peripheral neuropathy occurred in 8% of patients with mBC (Grade 4=0.4%) and 22% developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). Neuropathy lasting >1 year occurred in 5% of patients with mBC. Patients should be monitored for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less. 

Embryo-Fetal Toxicity: HALAVEN can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with HALAVEN and for 3.5 months following the final dose.

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy. Avoid in patients with congenital long QT syndrome.

Adverse Reactions
In patients with mBC receiving HALAVEN, the most common adverse reactions (≥25%) were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%). Febrile neutropenia (4%) and neutropenia (2%) were the most common serious adverse reactions. The most common adverse reaction resulting in discontinuation was peripheral neuropathy (5%).

Use in Specific Populations
Lactation: Because of the potential for serious adverse reactions in breastfed infants from eribulin mesylate, advise women not to breastfeed during treatment with HALAVEN and for 2 weeks after the final dose.

Hepatic and Renal Impairment: A reduction in starting dose is recommended for patients with mild or moderate hepatic impairment and/or moderate or severe renal impairment.

For more information about HALAVEN, click here for the full Prescribing Information.

HALAVEN® is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd.

About the Eisai and Merck Strategic Collaboration
In March 2018, Eisai and Merck, known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck's anti-PD-1 therapy KEYTRUDA.

In addition to ongoing clinical studies evaluating the KEYTRUDA plus LENVIMA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in 14 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer, pancreatic cancer and triple-negative breast cancer) across more than 20 clinical trials.

About Eisai
Eisai is a leading global research and development-based pharmaceutical company headquartered in Japan, with approximately 10,000 employees worldwide. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. We strive to realize our hhc philosophy by delivering innovative products in therapeutic areas with high unmet medical needs, including Oncology and Neurology. In the spirit of hhc, we take that commitment even further by applying our scientific expertise, clinical capabilities and patient insights to discover and develop innovative solutions that help address society's toughest unmet needs, including neglected tropical diseases and the Sustainable Development Goals.

For more information about Eisai, please visit www.eisai.com (for global), us.eisai.com (for U.S.) or www.eisai.eu (for Europe, Middle East, Africa), and connect with us on Twitter (U.S. and global) and LinkedIn (for U.S.).

LENVIMA® is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd.

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

 

SOURCE Eisai Inc.

For further information: Eisai Inc., Michele Randazzo, 551-579-4465, michele_randazzo@eisai.com

Type Press Release

Date Released May 17, 2021

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