vomiting, weight decreased, and constipation. Grade 3-4 adverse reactions and laboratory abnormalities which occurred in ≥ 5% of patients were hypertension, diarrhea, fatigue, palmar-plantar erythrodysesthesia syndrome, hyponatremia, hypophosphatemia, hypomagnesemia, lymphocytes decreased, anemia, hypokalemia, and GGT increased.
The dose was reduced in 60% of patients receiving CABOMETYX and in 24% of patients receiving everolimus. Twenty percent (20%) of patients received 20 mg CABOMETYX as their lowest dose. The most frequent adverse reactions leading to dose reduction in patients treated with CABOMETYX were: diarrhea, PPES, fatigue, and hypertension. Adverse reactions led to study treatment being held in 70% patients receiving CABOMETYX and in 59% patients receiving everolimus. Adverse reactions led to study treatment discontinuation in 10% of patients receiving CABOMETYX and in 10% of patients receiving everolimus. The most frequent adverse reactions leading to permanent discontinuation in patients treated with CABOMETYX were decreased appetite (2%) and fatigue (1%).
Table 1. Adverse Reactions Occurring in ≥ 10% Patients Who Received CABOMETYX
Adverse Reaction CABOMETYX
(n=331)* Everolimus
(n=322)
All
Grades† Grades
3-4 All
Grades† Grades
3-4
Percentage (%) of Patients
* One subject randomized to everolimus received cabozantinib. † National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 ‡ Includes PT terms abdominal pain, abdominal pain upper, and abdominal pain lower § Includes PT terms rash, rash erythematous, rash follicular, rash macular, rash papular, rash pustular, rash vesicular, genital rash, intermittent leg rash, rash on scrotum and penis, rash maculo-papular, rash pruritic, contact dermatitis, dermatitis acneiform ¶ Includes PT terms hypertension, blood pressure increased, hypertensive crisis, blood pressure fluctuation
Gastrointestinal Disorders
Diarrhea 74 11 28 2
Nausea 50 4 28 <1
Vomiting 32 2 14 <1
Stomatitis 22 2 24 2
Constipation 25 <1 19 <1
Abdominal pain‡ 23 4 13 2
Dyspepsia 12 <1 5 0
General Disorders and Administration Site Conditions
Fatigue 56 9 47 7
Mucosal inflammation 19 <1 23 3
Asthenia 19 4 16 2
Metabolism and Nutrition Disorders
Decreased appetite 46 3 34 <1
Skin and Subcutaneous Tissue Disorders
Palmar-plantar erythrodysesthesia syndrome 4 |
