Exelixis
See results from this combination therapy
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| INDICATION |
| CABOMETYX, in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). |
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| The 40-mg, once-daily starting dose of CABOMETYX is optimized for combination treatment with OPDIVO.1*
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| CheckMate-9ER Study Design |
| CheckMate-9ER was a randomized (1:1), open-label, phase 3 trial of CABOMETYX + OPDIVO vs sunitinib in 651 patients with previously untreated aRCC with a clear cell component. The trial evaluated CABOMETYX 40 mg (starting dose) PO once daily in combination with OPDIVO 240-mg flat dose IV every 2 weeks vs sunitinib 50 mg (starting dose) PO once daily for 4 weeks, followed by 2 weeks off, per cycle. The primary endpoint was PFS; secondary endpoints included OS, ORR, and safety. PFS and ORR were assessed by BICR. Quality of life was evaluated as an exploratory endpoint using the FKSI-19 scale, and the clinical significance is unknown. Other exploratory endpoints included biomarkers, pharmacokinetics, immunogenicity, and PFS-2. An updated efficacy
analysis was conducted when 271 events were observed based on the pre-specified number of events for the pre-planned final analysis of OS.1,3-7 |
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| Primary analysis: Discontinuation rates due to ARs in the CABOMETYX + OPDIVO arm were low1 |
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Permanent
discontinuation |
Dose interruption/
reduction |
| CABOMETYX or OPDIVO1 |
20% |
83% |
| CABOMETYX only1 |
8% |
46% |
| OPDIVO only1 |
7% |
3% |
| CABOMETYX and OPDIVO1 |
6%† |
21%†† |
| Sunitinib2 |
16.9% |
72.5% |
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| The discontinuation rate of CABOMETYX alone was 8%1 |
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| Permanently discontinue CABOMETYX for Grade 3 or 4 hemorrhage, development of a GI perforation or Grade 4 fistula, acute myocardial infarction or Grade 2 or higher cerebral infarction, Grade 3 or 4 arterial thromboembolic events or Grade 4 venous thromboembolic events, Grade 4 hypertension/hypertensive crisis or Grade 3 hypertension/hypertensive crisis that cannot be controlled, nephrotic syndrome, or reversible posterior leukoencephalopathy syndrome.1 |
| For patients being treated with CABOMETYX in combination with OPDIVO1: |
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If ALT or AST >3x ULN but ≤10x ULN without concurrent total bilirubin ≥2x ULN, both CABOMETYX and OPDIVO should be withheld until hepatic ARs recover to Grades 0 or 1. Corticosteroid therapy may be considered. Rechallenge with a single medicine or rechallenge with both medicines after recovery may be considered. If rechallenging with OPDIVO, refer to OPDIVO Prescribing Information. |
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If ALT or AST >10x ULN or >3x ULN with concurrent total bilirubin ≥2x ULN, both CABOMETYX and OPDIVO should be permanently discontinued. |
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| Select Important Safety Information |
| The full Prescribing Information for CABOMETYX includes Warnings and Precautions for: hemorrhage, perforations and fistulas, thrombotic events, hypertension and hypertensive crisis, diarrhea, palmar-plantar erythrodysesthesia, hepatotoxicity, adrenal insufficiency, proteinuria, osteonecrosis of the jaw, impaired wound healing, reversible posterior leukoencephalopathy syndrome, thyroid dysfunction, hypocalcemia, and embryo-fetal toxicity. |
| See additional Important Safety Information below. |
| CheckMate-9ER Adverse Reactions |
| Serious adverse reactions occurred in 48% of patients receiving CABOMETYX and nivolumab. The most frequent (≥2%) serious adverse reactions were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients.1 |
| The most common adverse reactions reported in ≥20% of patients treated with CABOMETYX and nivolumab were diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.1 |
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| INDICATION |
| CABOMETYX® (cabozantinib), in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). |
| IMPORTANT SAFETY INFORMATION |
| WARNINGS AND PRECAUTIONS |
| Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. Discontinue CABOMETYX for Grade 3-4 hemorrhage and before surgery. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena. |
| Perforations and Fistulas: Fistulas, including fatal cases, and Gastrointestinal (GI) perforations, including fatal cases, occurred in CABOMETYX patients. Monitor for signs and symptoms and discontinue in patients with Grade 4 fistulas or GI perforation. |
| Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Fatal thrombotic events have occurred. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events. |
| Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension including hypertensive crisis. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis. |
| Diarrhea: Diarrhea may be severe. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1, resume at a reduced dose. |
| Palmar-Plantar Erythrodysesthesia (PPE): Withhold CABOMETYX until PPE resolves or decreases to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE. |
| Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider withholding CABOMETYX and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity. |
| Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity. |
| Proteinuria: Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome. |
| Osteonecrosis of the Jaw (ONJ): Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution, resume at a reduced dose. |
| Impaired Wound Healing: Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established. |
| Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS. |
| Thyroid Dysfunction: Thyroid dysfunction, primarily hypothyroidism, has been observed with CABOMETYX. Assess for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitor for signs and symptoms during treatment. |
| Hypocalcemia: Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity. |
| Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women of the potential risk to fetus. Verify pregnancy status and advise use of effective contraception during treatment and for 4 months after last dose. |
| ADVERSE REACTIONS |
| The most common (≥20%) adverse reactions are: |
| CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection. |
| DRUG INTERACTIONS |
| Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice. |
| Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort. |
| USE IN SPECIFIC POPULATIONS |
| Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose. |
| Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment. |
| You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088. |
| Please see accompanying full Prescribing Information for additional important safety information. |
| If you would like more information about CABOMETYX, please visit CABOMETYXhcp.com. |
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