| |
Incidence, number (%)
|
ITC results
|
|---|
| |
COMBI-v
|
coBRIM
|
|---|
|
AE type
|
D + T (n = 350)
|
V (n = 349)
|
V (n = 246)
|
V + C (n = 247)
|
RR
|
LCI
|
UCI
|
p value
|
|---|
|
Abdominal pain
|
39(11.1)
|
32(9.2)
|
19(7.7)
|
25(10.1)
|
0.93
|
0.45
|
1.91
|
0.8378
|
|
Alopecia
|
23(6.6)
|
136(39)
|
73(29.7)
|
37(15.0)
|
0.33
|
0.19
|
0.58
|
0.0001
|
|
Anemia
|
26(7.4)
|
21(6.0)
|
20(8.1)
|
32(13.0)
|
0.77
|
0.36
|
1.67
|
0.5147
|
|
Arthralgia
|
93(26.6)
|
182(52.2)
|
99(40.2)
|
89(36.0)
|
0.57
|
0.42
|
0.77
|
0.0003
|
|
Asthenia
|
61(17.4)
|
58(16.6)
|
40(16.3)
|
43(17.4)
|
0.98
|
0.59
|
1.63
|
0.9368
|
|
Blurred vision
|
17(4.9)
|
18(5.2)
|
6(2.4)
|
25(10.1)
|
0.23
|
0.08
|
0.67
|
0.0075
|
|
Increased blood creatinine
|
15(4.3)
|
37(10.6)
|
20(8.1)
|
34(13.8)
|
0.24
|
0.11
|
0.52
|
0.0003
|
|
Chills
|
116(33.1)
|
28(8.0)
|
12(5.0)a
|
20(7.9)#
|
2.63
|
1.19
|
5.82
|
0.0167
|
|
Chorioretinopathy
|
2(<1)
|
1(<1)
|
1(<1)
|
31(12.6)
|
0.06
|
0.00
|
1.45
|
0.0843
|
|
Constipation
|
54(15.4)
|
25(7.2)
|
26(10.6)
|
24(9.7)
|
2.34
|
1.17
|
4.68
|
0.0160
|
|
Cough
|
77(22.0)
|
40(11.5)
|
30(12.2)
|
19(7.7)
|
3.04
|
1.59
|
5.83
|
0.0008
|
|
Cutaneous squamous cell carcinoma
|
5(1.4)
|
63(18.1)
|
27(11.3)a
|
7(2.8)#
|
0.32
|
0.10
|
1.09
|
0.0685
|
|
Decreased appetite
|
44(12.6)
|
70(20.1)
|
50(20.3)
|
46(18.6)
|
0.68
|
0.42
|
1.13
|
0.1361
|
|
Dermatitis acneiform
|
23(6.6)
|
20(5.7)
|
22(8.9)
|
34(13.8)
|
0.75
|
0.34
|
1.61
|
0.4539
|
|
Diarrhea
|
120(34.3)
|
136(39.0)
|
82(33.3)
|
150(60.7)
|
0.48
|
0.36
|
0.64
|
<0.0001
|
|
Dry skin
|
33(9.4)
|
67(19.2)
|
39(15.9)
|
35(14.2)
|
0.55
|
0.31
|
0.97
|
0.0407
|
|
Dysgeusia
|
23(6.6)
|
47(13.5)
|
26(10.6)
|
37(15.0)
|
0.34
|
0.18
|
0.67
|
0.0018
|
|
Edema peripheral
|
48(13.7)
|
42(12.0)
|
28(11.4)
|
31(12.6)
|
1.03
|
0.56
|
1.91
|
0.9165
|
|
Erythema
|
35(10.0)
|
42(12.0)
|
33(13.4)
|
24(9.7)
|
1.15
|
0.60
|
2.20
|
0.6795
|
|
Fatigue
|
110(31.4)
|
117(33.5)
|
80(32.5)
|
85(34.4)
|
0.89
|
0.64
|
1.23
|
0.4697
|
|
Headache
|
112(32.0)
|
84(24.1)
|
39(15.9)
|
41(16.6)
|
1.27
|
0.80
|
2.03
|
0.3172
|
|
Hyperkeratosis
|
18(5.1)
|
89(25.5)
|
75(30.5)
|
27(10.9)
|
0.56
|
0.30
|
1.06
|
0.0734
|
|
Hypertension
|
103(29.4)
|
82(23.5)
|
19(7.7)
|
37(15.0)
|
0.65
|
0.36
|
1.15
|
0.1399
|
|
Increased ALT
|
49(14.0)
|
61(17.5)
|
44(17.9)
|
65(26.3)
|
0.54
|
0.34
|
0.88
|
0.013
|
|
Increased AST
|
42(12.0)
|
46(13.2)
|
31(12.6)
|
60(24.3)
|
0.47
|
0.27
|
0.82
|
0.008
|
|
Increased blood ALP
|
26(7.4)
|
30(8.6)
|
22(8.9)
|
36(14.6)
|
0.53
|
0.26
|
1.08
|
0.0799
|
|
Increased blood CPK
|
10(2.9)
|
2(<1)
|
7(2.9)
|
80(32.4)
|
0.44
|
0.08
|
2.37
|
0.3378
|
|
Increased GGT
|
38(10.9)
|
33(9.5)
|
44(17.9)
|
54(21.9)
|
0.94
|
0.53
|
1.66
|
0.8292
|
|
Keratocanthoma
|
2(<1)
|
35(10.0)
|
20(8.4)a
|
2(<1)#
|
0.61
|
0.08
|
4.58
|
0.6269
|
|
Keratosis pilaris
|
4(1.1)
|
48(13.8)
|
26(10.6)
|
8(3.2)
|
0.27
|
0.08
|
0.97
|
0.0442
|
|
Myalgia
|
66(18.8)
|
56(16.1)
|
30(12.2)
|
28(11.3)
|
1.26
|
0.71
|
2.26
|
0.4298
|
|
Nausea
|
126(36.0)
|
130(37.3)
|
62(25.2)
|
102(41.3)
|
0.59
|
0.43
|
0.82
|
0.0015
|
|
Pain in extremity
|
45(12.9)
|
44(12.6)
|
35(14.2)
|
24(9.7)
|
1.49
|
0.80
|
2.79
|
0.2079
|
|
Photosensitivity reaction
|
15(4.3)
|
81(23.2)
|
93(37.8)
|
118(47.8)
|
0.15
|
0.08
|
0.26
|
<0.0001
|
|
Pruritus
|
36(10.3)
|
78(22.4)
|
46(18.7)
|
48(19.4)
|
0.44
|
0.26
|
0.74
|
0.0020
|
|
Pyrexia
|
193(55.1)
|
74(21.2)
|
56(22.8)
|
69(27.9)
|
2.12
|
1.45
|
3.09
|
0.0001
|
|
Rash
|
84(24.0)
|
150(43.0)
|
94(38.2)
|
98(39.7)
|
0.54
|
0.39
|
0.74
|
0.0001
|
|
Rash maculopapular
|
13(3.7)
|
28(8.0)
|
38(15.5)
|
38(15.4)
|
0.46
|
0.22
|
1.00
|
0.0490
|
|
SCC of skin
|
2(<1)
|
21(6.0)
|
31(12.6)
|
8(3.2)
|
0.37
|
0.07
|
1.88
|
0.2310
|
|
Skin papilloma
|
8(2.3)
|
82(23.5)
|
29(11.8)
|
12(4.9)
|
0.24
|
0.09
|
0.62
|
0.0033
|
|
Sun burn
|
3(<1)
|
51(14.6)
|
43(17.5)
|
34(13.8)
|
0.07
|
0.02
|
0.25
|
<0.0001
|
|
Vomiting
|
107(30.6)
|
55(15.8)
|
31(12.6)
|
60(24.3)
|
1.01
|
0.62
|
1.64
|
0.9798
|
-
a
N = 239; #
N = 254
-
AE adverse event, ALP alkaline phosphatase, ALT alanine aminotransferase, AST aspartate aminotransferase, CI confidence interval, CPK creatine phosphokinase, GGT gamma-glutamyltransferase, LCI lower 95% CI, RR risk ratio, SCC squamous cell carcinoma, UCI upper 95% CI
