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Prescribing Information
Important Safety Information
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LENVIMA® provides a superior PFS benefit
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LENVATINIB (LENVIMA) IS A NATIONAL COMPREHENSIVE CANCER NETWORK® (NCCN®)
PREFERRED AGENT BASED ON RESPONSE RATES2* |
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| Find out more about LENVIMA. |
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| Indication |
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| LENVIMA® (lenvatinib) is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC). |
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| Important Safety Information |
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| Warnings and Precautions |
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Hypertension reported in 73% of patients on LENVIMA vs 16% for placebo (44% vs 4% ≥grade 3). Blood pressure should be controlled prior to treatment. Withhold dose for grade 3 hypertension despite optimal antihypertensive therapy; resume at reduced dose when controlled at ≤grade 2. Discontinue for life-threatening hypertension |
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| Please see additional Important Safety Information below. |
| View full Prescribing Information. |
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| Powerful, durable response |
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65% ORR in the LENVIMA arm (95% CI: 59%-71%) vs 2% in the placebo arm (95% CI: 0%-4%); P<0.0011 |
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2% CR and 63% PR in the LENVIMA arm vs 0% CR and 2% PR in the placebo arm (P<0.001)1 |
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Median duration of response has not yet been reached in patients treated with LENVIMA, with a lower bound of 16.8 months (95% CI)3 |
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Median OS was not estimable between the LENVIMA and placebo arms (HR [95% CI]: 0.73 [0.50-1.07]; P=0.10)1 |
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PFS=progression-free survival; CI=confidence interval; NE=not estimable; HR=hazard ratio; ORR=objective response rate; CR=complete response; PR=partial response; OS=overall survival; SELECT=Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid; VEGF=vascular endothelial growth factor; VEGFR=vascular endothelial growth factor receptor; RECIST=Response Evaluation Criteria in Solid Tumors.
LENVIMA was studied in SELECT, a multicenter, randomized (2:1), double-blind, placebo-controlled trial conducted in 392 patients with locally recurrent or metastatic RAI-refractory DTC and radiographic evidence of disease progression within 12 months prior to randomization, confirmed by independent radiologic review. RAI-refractory was defined as 1 or more measurable lesions with no iodine uptake on RAI scan, iodine uptake with progression within 12 months of RAI therapy, or having received cumulative RAI activity of >600 mCi (22 GBq) with the last dose administered at least 6 months prior to study entry. Patients were randomized to receive LENVIMA 24 mg once daily (n=261) or placebo (n=131) until disease progression. Randomization was stratified by geographic region, prior VEGF/VEGFR-targeted therapy, and age. The primary end point was PFS, as determined by blinded, independent, radiologic review using RECIST 1.1. Independent review confirmation of disease progression was required prior to discontinuing patients from the randomization phase of the study. Secondary end points included ORR and OS. Patients in the placebo arm could receive LENVIMA following independent review confirmation of disease progression.1
*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thyroid Carcinoma V.2.2015. © National Comprehensive Cancer Network, Inc 2015. All rights reserved. Accessed November 23, 2015. To view the most recent and complete version of the guideline, go online to NCCN.org.
NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are
trademarks owned by the National Comprehensive Cancer Network, Inc.
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To learn more about LENVIMA, visit www.LENVIMA.com/hcp
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| Important Safety Information (cont'd) |
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Cardiac dysfunction reported in 7% of patients on LENVIMA vs 2% for placebo (2% vs 0% ≥grade 3). Monitor for signs/symptoms of cardiac decompensation. Withhold for grade 3 cardiac dysfunction. Resume at reduced dose or discontinue based on severity and persistence of cardiac dysfunction. Discontinue for grade 4 cardiac dysfunction |
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Arterial thromboembolic events reported in 5% of patients on LENVIMA vs 2% for placebo (3% vs 1% ≥grade 3). Discontinue following an arterial thrombotic event. The safety of resuming LENVIMA 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 |
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ALT and AST increases (≥grade 3) occurred in 4% and 5% of patients on LENVIMA vs 0% for placebo. Across clinical studies in which 1108 patients received LENVIMA, hepatic failure (including fatal events) was reported in 3 patients and acute hepatitis in 1 patient. Monitor liver function before initiation, then every 2 weeks for first 2 months, and at least monthly thereafter during treatment. Withhold dose for liver impairment ≥grade 3. Resume at reduced dose or discontinue based on severity/persistence of hepatotoxicity. Discontinue for hepatic failure |
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Proteinuria reported in 34% of patients on LENVIMA vs 3% for placebo (11% vs 0% ≥grade 3). Monitor for proteinuria before and during treatment. Withhold dose for ≥2 grams of proteinuria/24 hours. Resume at reduced dose when proteinuria is <2 gm/24 hours. Discontinue for nephrotic syndrome |
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Events of renal impairment reported in 14% of patients on LENVIMA vs 2% for placebo (3% vs 1% ≥grade 3). Withhold LENVIMA for grade 3 or 4 renal failure/impairment. Resume at reduced dose or discontinue, depending on severity/persistence of renal impairment |
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Events of gastrointestinal (GI) perforation or fistula reported in 2% of patients on LENVIMA vs 0.8% for placebo. Discontinue in patients who develop GI perforation or life-threatening fistula |
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QT/QTc interval prolongation reported in 9% of patients on LENVIMA vs 2% for placebo (2% vs 0% ≥grade 3). Monitor ECG in patients with congenital long QT syndrome, CHF, bradyarrhythmias, or patients taking drugs known to prolong the QT interval. Monitor and correct electrolyte abnormalities in all patients. Withhold dose for ≥grade 3 QT interval prolongation. Resume at reduced dose when QT prolongation resolves to grade 0, 1, or baseline |
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Hypocalcemia ≥grade 3 reported in 9% of patients on LENVIMA (2% for placebo). Monitor blood calcium levels at least monthly and replace calcium as necessary. Interrupt and adjust LENVIMA as necessary. In most cases, hypocalcemia responded to replacement and dose interruption/reduction |
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Across clinical studies in which 1108 patients received LENVIMA, reversible posterior leukoencephalopathy syndrome (RPLS) was reported in 3 patients. Withhold LENVIMA for RPLS until fully resolved. Resume at reduced dose or discontinue based on the severity and persistence of neurologic symptoms |
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Hemorrhagic events occurred in 35% of patients on LENVIMA vs 18% for placebo (2% vs 3% ≥grade 3). The most frequently reported hemorrhagic event was epistaxis (11% grade 1 and 1% grade 2). Discontinuation due to hemorrhagic events occurred in 1% of patients on LENVIMA. There was 1 fatal intracranial hemorrhage case among 16 patients who received LENVIMA and had CNS metastases at baseline. Withhold dose for grade 3 hemorrhage. Resume at reduced dose or discontinue, based on severity/persistence of hemorrhage. Discontinue for grade 4 hemorrhage |
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LENVIMA impairs exogenous thyroid suppression. In patients with a normal baseline TSH, elevation of TSH level above 0.5 mU/L was observed post baseline in 57% of patients on LENVIMA (14% for placebo). Monitor TSH levels monthly and adjust thyroid replacement medication as needed in patients with DTC |
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LENVIMA may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 2 weeks following completion of therapy |
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| Adverse Reactions |
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The most common adverse reactions observed in LENVIMA-treated patients vs placebo-treated patients were hypertension (73% vs 16%), fatigue (67% vs 35%), diarrhea (67% vs 17%), arthralgia/myalgia (62% vs 28%), decreased appetite (54% vs 18%), weight decreased (51% vs 15%), nausea (47% vs 25%), stomatitis (41% vs 8%), headache (38% vs 11%), vomiting (36% vs 15%), proteinuria (34% vs 3%), palmar-plantar erythrodysesthesia syndrome (32% vs 1%), abdominal pain (31% vs 11%), and dysphonia (31% vs 5%) |
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| Use in Specific Populations |
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Because of the potential for serious adverse reactions in nursing infants, advise women to discontinue breastfeeding during treatment |
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LENVIMA may result in reduced fertility in females of reproductive potential, and may result in damage to male reproductive tissues, leading to reduced fertility of unknown duration |
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| View the full Prescribing Information for LENVIMA. |
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| From, |
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| The LENVIMA Marketing Team |
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References:
1. LENVIMA [package insert]. Woodcliff Lake, NJ: Eisai Inc.; 2015. 2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Thyroid Carcinoma. Version 2.2015. www.NCCN.org. Published July 29, 2015. Accessed November 23, 2015. 3. Data on file, Eisai Inc. |
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