Table 3.
Incidence and management of potentially serious adverse effects associated with the use of oral cabozantinib tablets (Cabometyx®) in clinical trials in patients with renal cell carcinoma [7, 8]. Unless otherwise indicated, information applies to both the EU and USA
| Adverse effect (incidence in RCC trials [8]) | Prevention/management [7, 8] |
|---|---|
| Diarrhoea (74%, including 11% with grade 3) | Intolerable grade 2 or grade 3–4 diarrhoea that cannot be managed with standard antidiarrhoeal treatments: withhold cabozantinib until improvement to grade 1; resume cabozantinib at a ↓ dosagea |
| Fistulas (1%) and gastrointestinal perforations (1%) | Monitor pts for symptoms, including abscess and sepsis |
| Fistula or gastrointestinal perforation that cannot be appropriately managed: permanently discontinue cabozantinib | |
| Haemorrhage (3% with grade ≥ 3) | Pts with, or who are at risk for, severe haemorrhage: do not use cabozantinib |
| Severe haemorrhage: permanently discontinue cabozantinib | |
| Hypertension (44%, including 18% with grade ≥ 3) | Monitor BP before and during cabozantinib treatment; control BP before starting cabozantinib |
| Inadequately controlled BP despite medical management: withhold cabozantinib; resume cabozantinib at a ↓ dosagea once BP is controlled | |
| Hypertensive crisis or severe uncontrolled BP despite optimal medical management: permanently discontinue cabozantinib | |
| Nephrotic syndrome | Monitor urine protein regularly (EU) |
| Development of nephrotic syndrome: permanently discontinue cabozantinib | |
| PPES (42%, including 8% with grade 3) | Intolerable grade 2 or grade 3 PPES: withhold cabozantinib until improvement to grade 1; resume cabozantinib at a ↓ dosagea |
| RPLS | Pt presents with seizures, headache, visual disturbances, confusion or altered mental function: evaluate for RPLS |
| Development of RPLS: permanently discontinue cabozantinib | |
| Thrombotic events (9 and 1% with venous and arterial thromboembolism, respectively) | Development of acute myocardial infarction or any other clinically significant arterial thromboembolic complication: permanently discontinue cabozantinib |
| Pts who are at risk for, or have a history of, venous or arterial thromboembolism: use cabozantinib with caution (EU) | |
| Wound complications and surgery | Scheduled surgery (including dental): stop cabozantinib ≥ 28 days before surgery if possible |
| Resume cabozantinib once the wound is adequately healed (EU) | |
| Inadequate wound healing required medical intervention: discontinue cabozantinib (EU) |
Toxicity severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
BP blood pressure, PPES palmar-plantar erythrodysesthesia syndrome, pt patient, RCC renal cell carcinoma, RPLS reversible posterior leukoenecephalopathy syndrome, ↓ reduced
aFrom 60 mg/day to 40 mg/day, and from 40 mg/day to 20 mg/day