Dosing for CABOMETYX® (cabozantinib) with OPDIVO® (nivolumab)
Dosing for CABOMETYX® (cabozantinib) with OPDIVO® (nivolumab)
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CABOMETYX 40-mg, once-daily starting dose—optimized for combination treatment with OPDIVO1
Treatment with CABOMETYX should be continued until disease progression or unacceptable toxicity.1 Treatment with OPDIVO should be continued until disease progression or unacceptable toxicity for up to 2 years.1
- Administer CABOMETYX at least 1 hour before or at least 2 hours after eating1
- Swallow CABOMETYX tablets whole. Do not crush CABOMETYX tablets1
- Withhold CABOMETYX for at least 3 weeks prior to elective surgery, including dental surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed1
- Do not substitute CABOMETYX tablets with cabozantinib capsules1
- Do not administer CABOMETYX with food1
- Do not take a missed dose within 12 hours of the next dose1
- Modify the dosage for certain patients with hepatic impairment and for patients taking drugs known to strongly induce or inhibit CYP3A41
- When administering CABOMETYX in combination with OPDIVO for the treatment of aRCC, refer to the OPDIVO Prescribing Information1
Pharmacokinetics
- The predicted terminal half-life of CABOMETYX is approximately 99 hours1
Dose modifications1
CABOMETYX is a one-tablet dose even if dose adjustments are needed.1
COMBINATION | FIRST | SECOND |
---|---|---|
| | |
COMBINATION | 40 mg once daily |
---|---|
FIRST | 20 mg once daily |
SECOND | 20 mg once every other day* |
Tablets shown are not actual size.
*If previously receiving 20 mg once every other day, resume at same dose. If not tolerated, discontinue CABOMETYX.1
For intolerable Grade 2 ARs, Grade 3 or 4 ARs, and ONJ1
Withhold CABOMETYX
Wait until improvement or resolution (return to baseline or resolution to Grade 1)
Restart CABOMETYX at reduced dose
For patients who previously received CABOMETYX at 20 mg every other day,
RESUME CABOMETYX at 20 mg every other day if tolerated; otherwise, DISCONTINUE
Of the patients who needed to reduce their dosage, 72% required 1 dosage reduction2
20 mg once daily | 20 mg once every other day |
---|---|
50.3% | 8.1% |
The mean average daily dose of CABOMETYX was 30 mg/day2
Primary analysis: Discontinuation rates due to ARs in the CABOMETYX + OPDIVO arm were low1
Permanent discontinuation | Dose interruption/reduction | |
---|---|---|
CABOMETYX or OPDIVO1 | 20% | 83% |
CABOMETYX only1 | 8% | 46% |
OPDIVO only1 | 7% | 3% |
CABOMETYX and OPDIVO1 | 6%† | 21%‡ |
sunitinib3 | 16.9% | 72.5% |
- †
-
Due to the same AR at the same time.1
- ‡
-
Due to the same AR at the same time; 6% for both drugs sequentially.1
The discontinuation rate of CABOMETYX alone was 8%1
For patients being treated with CABOMETYX in combination with OPDIVO:
- 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 syndrome1
- 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 Information1
- If ALT or AST >10x ULN or >3x ULN with concurrent total bilirubin ≥2x ULN, both CABOMETYX and OPDIVO should be permanently discontinued1
When strong CYP3A4 inhibitors cannot be avoided1
Reduce the daily dose of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided.
Resume CABOMETYX at the dose that was used prior to initiating the strong CYP3A4 inhibitor 2 to 3 days after discontinuation of the strong inhibitor.
Examples of strong CYP3A4 inhibitors§:
- Boceprevir
- Clarithromycin
- Conivaptan
- Grapefruit juice
- Indinavir/ritonavir
- Itraconazole
- Ketoconazole
- Lopinavir/ritonavir
- Nefazodone
- Nelfinavir
- Posaconazole
- Ritonavir
- Saquinavir/ritonavir
- Voriconazole
When strong CYP3A4 inducers cannot be avoided1
Increase the daily dose of CABOMETYX if concomitant use with strong CYP3A4 inducers cannot be avoided.
For example, from 60 mg to 80 mg daily or from 40 mg to 60 mg daily, as tolerated
- Do not exceed a daily dose of 80 mg
Resume CABOMETYX at the dose that was used prior to initiating the strong CYP3A4 inducer 2 to 3 days after discontinuation of the strong inducer.
Examples of strong CYP3A4 inducers§:
- Rifampin
- Phenytoin
- Carbamazepine
- St. John’s wort
- §
-
Examples listed may not be comprehensive.
ALT=alanine aminotransferase; AR=adverse reaction; aRCC=advanced renal cell carcinoma; AST=aspartate aminotransferase; CYP3A4=cytochrome P450 family 3 subfamily A member 4; GI=gastrointestinal; IV=intravenous; ONJ=osteonecrosis of the jaw; RCC=renal cell carcinoma; ULN=upper limit of normal.
References:
- CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc.
- Data on file. Exelixis, Inc.
- Data on file. Final Clinical Study Report for Study CA2099ER. Bristol Myers Squibb.