Safety results in the CELESTIAL trial1
Adverse Reactions (ARs) occurring at a higher incidence in patients treated with CABOMETYX® (cabozantinib) (between-arm difference of ≥5% [All Grades] or ≥2% [Grade 3-4])
Percentage (%) of Patients | ||||
CABOMETYX (n=467) |
placebo (n=237) |
|||
All Grades* | Grade 3-4 | All Grades* | Grade 3-4 | |
Gastrointestinal | ||||
Diarrhea | 54 | 10 | 19 | 2 |
Nausea | 31 | 2 | 18 | 2 |
Vomiting | 26 | <1 | 12 | 3 |
Stomatitis | 13 | 2 | 2 | 0 |
Dyspepsia | 10 | 0 | 3 | 0 |
General | ||||
Fatigue | 45 | 10 | 30 | 4 |
Asthenia | 22 | 7 | 8 | 2 |
Mucosal inflammation | 14 | 2 | 2 | <1 |
Metabolism and Nutrition | ||||
Decreased appetite | 48 | 6 | 18 | <1 |
Skin and Subcutaneous Tissue | ||||
PPE | 46 | 17 | 5 | 0 |
Rash† | 21 | 2 | 9 | <1 |
Vascular | ||||
Hypertension‡ | 30 | 16 | 6 | 2 |
Investigations | ||||
Weight decreased | 17 | 1 | 6 | 0 |
Nervous System | ||||
Dysgeusia | 12 | 0 | 2 | 0 |
Endocrine | ||||
Hypothyroidism | 8 | <1 | <1 | 0 |
Respiratory, Thoracic, and Mediastinal | ||||
Dysphonia | 19 | 1 | 2 | 0 |
Dyspnea | 12 | 3 | 10 | <1 |
Musculoskeletal and Connective Tissue | ||||
Pain in extremity | 9 | <1 | 4 | 1 |
Muscle spasms | 8 | <1 | 2 | 0 |
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NCI-CTCAE v4.0
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Includes the following terms: rash, rash erythematous, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, rash vesicular, dermatitis, dermatitis acneiform, dermatitis contact, dermatitis diaper, dermatitis exfoliative, dermatitis infected.
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Includes the following terms: hypertension, blood pressure diastolic increased, blood pressure increased.
Laboratory Abnormalities occurring at a higher incidence in patients treated with CABOMETYX between-arm difference of ≥5% [All Grades] or ≥2% [Grade 3-4])1
Percentage (%) of Patients | ||||||
CABOMETYX (n=467) |
placebo (n=237) |
|||||
All Grades | Grade 3-4 | All Grades | Grade 3-4 | |||
Chemistry | ||||||
Increased LDH | 84 | 9 | 29 | 2 | ||
Increased ALT | 73 | 12 | 37 | 6 | ||
Increased AST | 73 | 24 | 46 | 19 | ||
Hypoalbuminemia | 51 | 1 | 32 | 1 | ||
Increased ALP | 43 | 8 | 38 | 6 | ||
Hypophosphatemia | 25 | 9 | 8 | 4 | ||
Hypokalemia | 23 | 6 | 6 | 1 | ||
Hypomagnesemia | 22 | 3 | 3 | 0 | ||
Increased amylase | 16 | 2 | 9 | 2 | ||
Hypocalcemia | 8 | 2 | 0 | 0 | ||
Hematology | ||||||
Decreased platelets | 54 | 10 | 16 | 1 | ||
Neutropenia | 43 | 7 | 8 | 1 | ||
Increased hemoglobin | 8 | 0 | 1 | 0 |
The overall efficacy results in the CELESTIAL trial were achieved in the context of dose modifications1
CABOMETYX vs placebo |
|
---|---|
Dose withholds2 | 84% 37% |
Median duration of each dose withhold2 | 9 days |
Dose reductions3 | 62% 13% |
Discontinuations2 | 16% 3% |
Mean average daily dose2 | 37 mg |
The most frequent adverse reactions or laboratory abnormalities leading to dose reduction of CABOMETYX were: palmar-plantar erythrodysesthesia, diarrhea, fatigue, hypertension, and increased AST. The most frequent adverse reactions leading to permanent discontinuation of CABOMETYX were palmar-plantar erythrodysesthesia (2%), fatigue (2%), decreased appetite (1%), diarrhea (1%), and nausea (1%).1
ALP=alkaline phosphatase; ALT=alanine aminotransferase; aRCC=advanced renal cell carcinoma; AST=aspartate aminotransferase; HCC=hepatocellular carcinoma; LDH=lactate dehydrogenase; NCI-CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; PPE=palmar-plantar erythrodysesthesia.
References:
- CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc, 2021.
- Data on file. Exelixis, Inc. 3. Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54-63.