CABOMETYX® initial FDA approval in advanced RCC was based on the METEOR trial

METEOR trial design1-3

Randomized, open-label, phase 3 trial that compared the efficacy of CABOMETYX® (cabozantinib) with that of everolimus in patients with advanced RCC who had received at least one prior treatment.*

Primary endpoint=progression-free survival (PFS).

Secondary efficacy endpoints=overall survival and objective response rate.

Tumor assessment every 8 weeks for the first 12 months; then every 12 weeks thereafter.

*Anti-angiogenic therapy.
Dose reductions were allowed in both arms.
The primary PFS analysis was conducted in the first 375 subjects randomized to treatment. The intent-to-treat (ITT) population included all 658 patients.3
§Patients received treatment until disease progression or experiencing unacceptable toxicity. Patients in both arms who had disease progression could continue treatment at the discretion of the investigator.3

Inclusion criteria1-3:

  • Clear cell component
  • Measurable disease as defined by RECIST 1.1
  • Radiographic progression within 6 months of enrollment
  • Radiographic progression during treatment with a VEGFR-TKI or within 6 months of last dose
  • No limit to the number of prior therapies
  • Prior treatment with antibodies targeting PD-1/PD-L1 allowed
  • Brain metastases allowed if adequately treated
  • Patients had to have a Karnofsky Performance score ≥70%

Prespecified stratification2:

  • MSKCC risk groups: favorable, intermediate, poor
  • Number of prior VEGFR-TKIs: 1, ≥2

MSKCC=Memorial Sloan Kettering Cancer Center.
VEGFR=Vascular endothelial growth factor receptor.
TKI=Tyrosine kinase inhibitor.
PD-1/PD-L1=Programmed death 1/programmed death ligand 1.
RECIST=Response Evaluation Criteria in Solid Tumors.

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Indication

CABOMETYX® (cabozantinib) is a kinase inhibitor indicated for the treatment of patients with advanced renal cell carcinoma (RCC).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

  • Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In RCC trials, the incidence of Grade ≥3 hemorrhagic events was 3% in CABOMETYX patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
  • Gastrointestinal (GI) Perforations and Fistulas: In RCC trials, GI perforations were reported in 1% of CABOMETYX patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, fistulas were reported in 1% of CABOMETYX patients. Monitor patients for symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a GI perforation or a fistula that cannot be appropriately managed.
  • Thrombotic Events: Thrombotic events increased with CABOMETYX. In RCC trials, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
  • Hypertension and Hypertensive Crisis: Treatment-emergent hypertension, including hypertensive crisis, increased with CABOMETYX. In RCC trials, hypertension was reported in 44% (18% Grade ≥3) of CABOMETYX patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX if there is evidence of hypertensive crisis or for severe hypertension that cannot be controlled with antihypertensive therapy or medical management.
  • Diarrhea: In RCC trials, diarrhea occurred in 74% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.
  • Palmar-Plantar Erythrodysesthesia (PPE): In RCC trials, PPE occurred in 42% of CABOMETYX patients. Grade 3 PPE occurred in 8% of CABOMETYX patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.
  • Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
  • Embryo-fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.

ADVERSE REACTIONS

The most commonly reported (≥25%) adverse reactions were: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.

DRUG INTERACTIONS

  • Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
  • Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.

USE IN SPECIFIC POPULATIONS

  • Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
  • Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

Please see accompanying full Prescribing Information by clicking here.

IMDC=International Metastatic Renal Cell Carcinoma Database Consortium; TKI=tyrosine kinase inhibitor.

Reference: 1. CABOMETYX® (cabozantinib) Prescribing Information. Exelixis Inc., 2017.

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Indication and Important Safety Information

Indication

CABOMETYX® (cabozantinib) is a kinase inhibitor indicated for the treatment of patients with advanced renal cell carcinoma (RCC).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

  • Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In RCC trials, the incidence of Grade ≥3 hemorrhagic events was 3% in CABOMETYX patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.