00)
Placebo
(n=253)
Grade
Grade
All
%
≥ 3
%
All
%
≥ 3
%
General disorders and administration site conditions
Asthenia/fatigue Pain
Fever
64 29 28
15 3 2
46
21
15
9
2
0
Metabolism and nutrition disorders
Decreased appetite and food intake
47
5
28
4
Skin and subcutaneous tissue disorders
HFSR/PPE
Rash
45
26
17
6
7
4
0
<1
Gastrointestinal disorders
Diarrhea
Mucositis
43
33
8
4
17
5
2
0
Investigations
Weight loss
32
<1
10
0
Infections and infestations
Infection
31
9
17
6
Vascular disorders
Hypertension
Hemorrhage*
30
21
8
2
8
8
<1
<1
Respiratory, thoracic and mediastinal disorders
Dysphonia
30
0
6
0
Nervous system disorders
Headache
10
<1
7
0
Other clinically important adverse reactions observed more commonly in less than 10% of Stivarga-treated patients and at a higher incidence than in placebo-treated patients included the following: alopecia (7.6% vs. 1.6%), taste disorder (7.6% vs. 2.4%), musculoskeletal stiffness (6.0% vs. 2.0%), dry mouth (4.8% vs. 2.0%), hypothyroidism (4.2% vs. 0.4%), tremor (2.0% vs. 0.0), gastroesophageal reflux (1.4% vs. 0.0), and gastrointestinal fistula (0.8% vs. 0.4%).
Keratoacanthoma/squamous cell carcinoma of the skin occurred in 0.09% of 1100 Stivarga-treated patients across open-label or placebo-controlled clinical trials.
Laboratory Abnormalities
Laboratory abnormalities observed in Study 1 are shown in Table 2.
Table 2: Laboratory test abnormalities reported in Study 1
Laboratory Parameter
Stivarga plus BSC
(n=500*)
Placebo plus BSC
(n=253*)
Grade**
Grade**
All
%
3
%
4
%
All
%
3
%
4
%
Blood and lymphatic system disorders
Anemia
79
5
1
66
3
0
Thrombocytopenia
41
2
<1
17
<1
0
Neutropenia
3
1
0
0
0
0
Lymphopenia
54
9
0
34
3
0
Metabolism and nutrition disorders
Hypocalcemia
59
1
<1
18
1
