419 476
Table 4 – Treatment-related adverse events in randomized clinical trials on immune checkpoint inhibitors in urological cancer
Treatment
Patients
(
n
)
Any grade
AEs
Grade
3–4 AEs
Types of grade 3–4 AEs
Grade
3–4 IR AEs
Types of grade 3–4 IR AEs
AEs leading to
discontinuation
aAEs leading
to death
bUrothelial cell cancer
Bellmunt et al (2017)
[23]
Pembrolizumab 270
162
(61%)
40
(15%)
Fatigue (1.1%), diarrhea (1.1%), anemia (0.8%), nausea
(0.4%), asthenia (0.4%), decreased neutrophil count (0.4%)
12
(4.5%)
Pneumonitis (2.3%), colitis (1.1%),
nephritis (0.8%), severe skin
reaction (0.4%), adrenal
insufficiency (0.4%)
12
(4.5%)
4
(1.5%)
Chemotherapy
272
230
(90%)
126
(49%)
Neutropenia (13.3%), decreased neutrophil count (12.2%),
anemia (7.8%), fatigue (4.3%), constipation (3.1%), asthenia
(2.7%), peripheral sensory neuropathy (2.0%), nausea
(1.6%), decreased appetite (1.2%), diarrhea (0.8%),
peripheral neuropathy (0.8%), alopecia (0.8%), pruritus
(0.4%)
4
(1.6%)
Severe skin reaction (1.2%),
myositis (0.4%)
28
(11%)
4
(1.6%)
Renal cell cancer
Motzer et al (2015)
[26]
Nivolumab
406
319
(79%)
76
(19%)
Fatigue (2%), anemia (2%), diarrhea (1%), dyspnea (1%),
pneumonitis (1%), hyperglycemia (1%), decreased appetite
(
<
1%), rash (
<
1%), nausea (
<
1%)
NA
NA
31
(8%)
0
Everolimus
397
349
(88%)
145
(37%)
Anemia (8%), hypertriglyceridemia (5%), hyperglycemia
(4%), stomatitis (4%), fatigue (3%), pneumonitis (3%),
mucosal inflammation (3%), nausea (1%), diarrhea (1%),
decreased appetite (1%), rash (1%), dyspnea (1%), peripheral
edema (1%)
NA
NA
52
(13%)
2
Motzer et al (2015)
[25]
Nivolumab
0.3 mg/kg
59
44
(75%)
3
(5%)
Nausea (2%)
NA
Increased AST (2%), increased ALT
(2%)
1
(2%)
0
Nivolumab
2 mg/kg
54
36
(67%)
9
(17%)
Nausea (2%), pruritus (2%)
NA
Pruritus (2%), hypothyroidism
(2%), gastrointestinal (2%),
increased AST (2%), increased ALT
(2%)
6
(11%)
0
Nivolumab
10 mg/kg
54
42
(78%)
7
(13%)
Arthralgia (2%)
NA
0
4
(7%)
0
Choueiri et al (2016)
[24]
Nivolumab
0.3 mg/kg
22
22
(100%)
15
(68%)
Constipation (5%), increased AST (5%), increased ALT (5%),
acute renal failure (5%), pneumonitis (5%)
0
0
NA
NA
Nivolumab
2 mg/kg
22
22
(100%)
8
(36%)
Fatigue (9%), constipation (5%)
0
0
NA
NA
Nivolumab
10 mg/kg
23
23
(100%)
13
(57%)
Increased AST (9%), colitis (4%), diarrhea (4%), increased
ALT (4%), increased blood bilirubin (4%), acute renal failure
(4%), pneumonitis (4%), skin (4%)
1
(4%)
Skin (4%)
NA
NA
Treatment naive
Nivolumab
10 mg/kg
24
24
(100%)
12
(50%)
Colitis (8%), fatigue (4%), diarrhea (4%), endocrine (4%),
hypersensitivity/infusion reaction (4%), infusion-related
reaction (4%)
0
0
NA
NA
Prostate cancer
Beer et al (2017)
[27]Ipilimumab
399
325
(82%)
158
(40%)
Diarrhea (15%), rash (3%), fatigue (3%), nausea (2%),
decreased appetite (1%), vomiting (1%), pruritus (
<
1%)
125
(31%)
NA
114
(29%)
9
(2%)
Placebo
199
98
(49%)
11
(6%)
Fatigue (1%), pruritus (
<
1%)
3
(2%)
NA
5
(3%)
0
Kwon et al (2014)
[28]
Radiotherapy
with
ipilimumab
393
295
(75%)
NA
NA
101
(26%)
NA
4
(1%)
Radiotherapy
with placebo
396
180
(45%)
NA
NA
11
(3%)
NA
0
AEs = adverse events; IR = immune related; NA = not available; AST = aspartate aminotransferase; ALT = alanine aminotransferase; NA = not available.
a
Treatment-related events of any grade leading to treatment discontinuation.
b
Treatment-related events of any grade leading to patient death.
E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 4 1 1 – 4 2 3
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