, and all patients had metastatic melanoma. All patients received 2 mg once-daily doses of Mekinist. The incidence of RPED and RVO are obtained from the 1,749 patients from all clinical trials with Mekinist.
Table 2 presents adverse reactions identified from analyses of Trial 1, [see Clinical Studies (14.1)] a randomized, open-label trial of patients with BRAF V600E or V600K mutation-positive melanoma receiving Mekinist (N = 211) 2 mg orally once daily or chemotherapy (N = 99) [either dacarbazine 1,000 mg/m2 every 3 weeks or paclitaxel 175 mg/m2 every 3 weeks]. Patients with abnormal LVEF, history of acute coronary syndrome within 6 months, or current evidence of Class II or greater congestive heart failure (New York Heart Association) were excluded from Trial 1. The median duration of treatment with Mekinist was 4.3 months. In Trial 1, 9% of patients receiving Mekinist experienced adverse reactions resulting in permanent discontinuation of trial medication. The most common adverse reactions resulting in permanent discontinuation of Mekinist were decreased left ventricular ejection fraction (LVEF), pneumonitis, renal failure, diarrhea, and rash. Adverse reactions led to dose reductions in 27% of patients treated with Mekinist. Rash and decreased LVEF were the most common reasons cited for dose reductions of Mekinist.
Table 2. Selected Adverse Reactions Occurring in ≥10% of Patients Receiving Mekinist and at a Higher Incidence than in the Control Arma Adverse Reactions
Mekinist
Chemotherapy
(N = 211)
(N = 99)
All Gradesb
Grades
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 = 3
