3 and 4c
 All Gradesb
 Grades

3 and 4c
 
Skin and subcutaneous tissue disorders
        
Rash
 57
 8
 10
 0
 
Dermatitis acneiform
 19
 <1
 1
 0
 
Dry skin
 11
 0
 0
 0
 
Pruritus
 10
 2
 1
 0
 
Paronychia
 10
 0
 1
 0
 
Gastrointestinal disorders
        
Diarrhea
 43
 0
 16
 2
 
Stomatitisd
 15
 2
 2
 0
 
Abdominal paine
 13
 1
 5
 1
 
Vascular disorders
        
Lymphedemaf
 32
 1
 4
 0
 
Hypertension
 15
 12
 7
 3
 
Hemorrhageg
 13
 <1
 0
 0
aEvents included are higher in the trametinib arm compared with chemotherapy by ≥5% in overall incidence or by ≥2% Grade 3-4 adverse reactions higher in trametinib arm compared with chemotherapy.

b National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.

c Grade 4 adverse reactions were limited to rash (n = 1) in trametinib arm and diarrhea (n = 1) in the chemotherapy arm.

d Includes the following terms: stomatitis, aphthous stomatitis, mouth ulceration, and mucosal inflammation.

e Includes the following terms: abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness.

f Includes the following terms: lymphedema, edema, and peripheral edema.

g Includes the following terms: epistaxis, gingival bleeding, hematochezia, rectal hemorrhage, melena, vaginal hemorrhage, hemorrhoidal hemorrhage, hematuria, and conjunctival hemorrhage.

Other clinically important adverse reactions observed in ≤10% of patients (N = 329) treated with MEKINIST were:

Nervous System Disorders: Dizziness, dysgeusia.

Ocular Disorders: Vision blurred, dry eye.

Infections and Infestations: Folliculitis, rash pustular, cellulitis.

Cardiac Disorders: Bradycardia.

Gastrointestinal Disorders: Xerostomia.

Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis.

Table 3. Percent-Patient Incidence of Laboratory Abnormalities Occurring at a Higher Incidence in Patients Treated With MEKINIST in Trial 1 [Between Arm Difference of ≥5% (All Grades) or ≥2% (Grades 3 or 4)a] Preferred Term
 MEKINIST
 Chemotherapy
 
(N = 211)
 (N = 99)
 
All Grades
 Grades

3 and 4
 All Grades
 Grades

3 and 4
 
Increased Aspartate aminotransferase (AST)
 60
 2
 16
 1
 
Increased Alanine aminotransferase (ALT)
 39
 3
 20
 3
 
Hypoalbuminemia