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Eisai Inc. is proud to announce a new approval: LENVIMA® in combination with everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy.1
Find out more about LENVIMA.
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The efficacy and safety of LENVIMA + everolimus were evaluated in Study 205—a multicenter, randomized, phase 2 trial in patients with advanced or metastatic RCC who had previously received anti-angiogenic therapy.1
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CI=confidence interval; HR=hazard ratio.
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Study 205 randomized 153 patients with advanced or metastatic RCC who had previously received anti-angiogenic therapy 1:1:1 to LENVIMA 18 mg + everolimus 5 mg, LENVIMA 24 mg monotherapy, or everolimus 10 mg monotherapy. All medications were administered orally once daily. Patients were required to have histological confirmation of clear cell RCC and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were stratified by hemoglobin level (≤13 g/dL vs >13 g/dL for males and ≤11.5 g/dL vs >11.5 g/dL for females) and corrected serum calcium (≥10 mg/dL vs <10 mg/dL). The major efficacy outcome measure was PFS. Other efficacy outcome measures included objective response rate (ORR) and overall survival (OS).
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14.6-month (95% CI: 5.9-20.1) median PFS with LENVIMA + everolimus vs 5.5 months (95% CI: 3.5-7.1) with everolimus alone (HR [95% CI]: 0.37 [0.22-0.62])1 |
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26 events (51%) occurred in the LENVIMA + everolimus arm vs 37 events (74%) in the everolimus arm* |
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| Powerful response1 |
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37% confirmed ORR (95% CI: 24%-52%) with LENVIMA + everolimus vs 6% with everolimus (95% CI: 1%-17%) |
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2% of patients in the LENVIMA + everolimus arm achieved a complete response vs 0 patients in the everolimus arm |
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35% of patients in the LENVIMA + everolimus arm achieved a partial response vs 6% of patients in the everolimus arm |
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| Indication |
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| LENVIMA® (lenvatinib) is indicated in combination with everolimus for the treatment of patients with advanced RCC following one prior anti-angiogenic therapy. |
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| Important Safety Information |
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| Warnings and Precautions |
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Hypertension was reported in 42% of patients on LENVIMA + everolimus vs 10% with everolimus alone (13% vs 2% grade 3). Blood pressure should be controlled prior to treatment and monitored throughout. 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. |
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| View full Prescribing Information. |
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| Clinically meaningful OS benefit1 |
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25.5-month (95% CI: 16.4-32.1) median OS with LENVIMA + everolimus vs 15.4 months (95% CI: 11.8-20.6) with everolimus alone (HR [95% CI]: 0.67 [0.42-1.08])† |
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Learn more about LENVIMA + everolimus by contacting your Eisai sales representative or by visiting LenvimaAdvancedRCC.com |
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Twenty-one patients (41%) who received LENVIMA + everolimus progressed vs 35 patients (70%) who received everolimus. Death occurred in 5 patients (10%) who received LENVIMA + everolimus vs 2 patients (4%) who received everolimus. |
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Analysis was conducted after 63% of deaths had occurred in the LENVIMA + everolimus arm and 74% of deaths had occurred in the everolimus arm. |
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| Important Safety Information (cont'd) |
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| Warnings and Precautions |
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Cardiac dysfunction was reported in 10% of patients on LENVIMA + everolimus vs 6% with everolimus alone (3% vs 2% 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 were reported in 2% of patients on LENVIMA + everolimus vs 6% with everolimus alone (2% vs 4% 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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Across clinical studies in which 1,160 patients received LENVIMA monotherapy, hepatic failure (including fatal events) was reported in 3 patients and acute hepatitis in 1 patient. ALT and AST increases (grade ≥3) occurred in 3% of patients on LENVIMA + everolimus vs 2% and 0% with everolimus alone, respectively. Monitor liver function before initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Withhold dose for liver impairment grade ≥3 until resolved to grade 0, 1, or baseline. Resume at reduced dose or discontinue based on severity/persistence of hepatotoxicity. Discontinue for hepatic failure |
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Proteinuria was reported in 31% of patients on LENVIMA + everolimus vs 14% with everolimus alone (8% vs 2% grade 3). Monitor for proteinuria before and during treatment. Withhold dose for proteinuria ≥2 g/24 h. Resume at reduced dose when proteinuria is <2 g/24 h. Discontinue for nephrotic syndrome |
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Diarrhea was reported in 81% of patients on LENVIMA + everolimus vs 34% with everolimus alone (19% vs 2% grade 3). Initiate prompt medical management for the development of diarrhea. Monitor for dehydration. Withhold dose for diarrhea grade ≥3. Resume at a reduced dose when diarrhea resolves to grade 1 or baseline. Discontinue for grade 4 diarrhea despite medical management |
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Events of renal impairment were reported in 18% of patients on LENVIMA + everolimus vs 12% with everolimus alone (10% vs 2% 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. Active management of diarrhea and any other gastrointestinal (GI) symptoms should be initiated for grade 1 events |
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Events of GI perforation, abscess, or fistula (grade ≥3) were reported in 2% of patients on LENVIMA + everolimus vs 0% with everolimus alone. Discontinue in patients who develop GI perforation or life-threatening fistula |
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QTc interval increases >60 ms were reported in 11% of patients on LENVIMA + everolimus (6% >500 ms) vs 0% with everolimus alone. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or patients taking drugs known to prolong the QT interval. Monitor and correct electrolyte abnormalities in all patients. Withhold dose for QTc interval prolongation >500 ms. Resume at reduced dose when QTc prolongation resolves to baseline |
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Hypocalcemia (grade ≥3) was reported in 6% of patients on LENVIMA + everolimus vs 2% with everolimus alone. Monitor blood calcium levels at least monthly and replace calcium as necessary. Interrupt and adjust LENVIMA as necessary |
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Across clinical studies in which 1,160 patients received LENVIMA monotherapy, reversible posterior leukoencephalopathy syndrome (RPLS) was reported in 4 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 34% of patients on LENVIMA + everolimus vs 26% with everolimus alone (8% vs 2% grade ≥3). The most frequently reported hemorrhagic event was epistaxis (23% for LENVIMA + everolimus vs 24% with everolimus alone). There was 1 fatal cerebral hemorrhage case. Discontinuation due to hemorrhagic events occurred in 3% of patients on LENVIMA + everolimus. Consider the risk of severe or fatal hemorrhage associated with tumor invasion/infiltration of major blood vessels (eg, carotid artery). 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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Grade 1 or 2 hypothyroidism occurred in 24% of patients on LENVIMA + everolimus vs 2% with everolimus alone. In patients with normal or low thyroid-stimulating hormone (TSH) at baseline, elevation of TSH was observed postbaseline in 60% of patients on LENVIMA + everolimus vs 3% with everolimus alone. Monitor thyroid function prior to treatment initiation and monthly thereafter. Treat hypothyroidism according to standard medical practice to maintain a euthyroid state |
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LENVIMA can 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 patients treated with LENVIMA + everolimus vs everolimus alone were diarrhea (81% vs 34%), fatigue (73% vs 40%), arthralgia/myalgia (55% vs 32%), decreased appetite (53% vs 18%), vomiting (48% vs 12%), nausea (45% vs 16%), stomatitis/oral inflammation (44% vs 50%), hypertension/increased blood pressure (42% vs 10%), peripheral edema (42% vs 20%), cough (37% vs 30%), abdominal pain (37% vs 8%), dyspnea/exertional dyspnea (35% vs 28%), rash (35% vs 40%), weight decreased (34% vs 8%), hemorrhagic events (32% vs 26%), and proteinuria/urine protein present (31% vs 14%) |
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Adverse reactions led to dose reductions or interruption in 89% of patients receiving LENVIMA + everolimus and in 54% of patients receiving everolimus. The most common adverse reactions (≥5%) resulting in dose reductions in the LENVIMA + everolimus–treated group 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 the LENVIMA + everolimus–treated group and in 12% of patients in the everolimus-treated group |
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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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| Reference: 1. LENVIMA [package insert]. Woodcliff Lake, NJ: Eisai Inc.; 2016. |
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