Sorry, you need to enable JavaScript to visit this website.

SUTENT (sunitinib capsules) Adverse Reactions

Pfizer recognizes the public concern in relation to COVID-19, which continues to evolve. Click here to learn how we are responding.
Pfizer reconnaît les préoccupations du grand public concernant la situation liée à la COVID-19, qui continue d'évoluer. Cliquez ici pour savoir comment nous avons réagi.

Adverse Reactions

Overview

The data described below reflect exposure to SUTENT in 660 patients who participated in a placebo-controlled trial (n=202) for the treatment of GIST, an active-controlled trial (n=375) for the treatment of MRCC or a placebo-controlled trial (n=83) for the treatment of pancreatic NET. The GIST and MRCC patients received a starting oral dose of 50 mg daily on Schedule 4/2 in repeated cycles, and the pancreatic NET patients received a starting oral dose of 37.5 mg daily without scheduled off-treatment periods. Most adverse events are reversible and do not need to result in discontinuation. If necessary, these events can be managed through dose adjustments or interruptions.

The most common treatment-related adverse reactions (≥20%) in patients with GIST, MRCC or pancreatic NET are fatigue, asthenia, diarrhea, nausea, mucositis/stomatitis, vomiting, dyspepsia, abdominal pain, constipation, hypertension, rash, hand-foot syndrome, skin discoloration, dry skin, hair color changes, altered taste, anorexia, and bleeding. The potentially serious adverse reactions of left ventricular dysfunction, QT interval prolongation, hemorrhage, hypertension, thyroid dysfunction, and adrenal function are discussed in WARNINGS AND PRECAUTIONS. Other adverse reactions reported in studies of GIST, MRCC and pancreatic NET studies are described below.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse Reactions in GIST Placebo-Controlled Study (Study A)

The median duration of blinded study treatment was 2 cycles for patients on the SUTENT arm (mean 3, range 0-9) and one cycle (mean 1.6, range 0-6) for patients on placebo at the time of the interim analysis. Dose reductions occurred in 23 patients (11%) on SUTENT and none on placebo. Dose interruptions occurred in 57 patients (28%) on SUTENT and 20 (20%) on placebo. The rate of permanent discontinuation due to treatment-related, non-fatal adverse events was 9% (19/202) vs. 8% (8/102), SUTENT vs. placebo.

Most treatment-related adverse events, reported for both treatment arms were Grade 1 or 2 in severity. Grade 3 or 4 treatment-related adverse events were reported in 48% of SUTENT patients and 29% of placebo patients, respectively, in the double-blind treatment phase of the trial. Fatigue was the most common treatment-related adverse event of any maximum severity grade reported for 42% of SUTENT patients and 36% of placebo patients. Diarrhea, nausea, stomatitis, altered taste, skin abnormalities, hypertension and bleeding were all more common in patients receiving SUTENT than in those receiving placebo. Alopecia has been observed in 9 (4.5%) subjects exposed to sunitinib in Study A as compared to 1 (1%) subject exposed to placebo. All events were NCI CTC Grade 1 severity. Hair color changes have been observed in 14 (6.9%) subjects exposed to sunitinib in Study A as compared to 2 (2%) subjects exposed to placebo. Table 1 presents the treatment-emergent adverse events commonly reported (≥ 10% of patients) in Study A.

Table 1: Treatment-Emergent Adverse Events Reported in at Least 10% of GIST Patients Who Received SUTENT or Placebo in Study A in the Double-Blind Treatment Phase of Study A
Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
PPE: Palmar plantar erythrodyaesthesia syndrome
NOS: Not otherwise specified

 

GIST

 

SUTENT (n=202)

Placebo (n=102)

Adverse Event, n (%)

All Grades

Grade 3/4

All Grades

Grade 3/4

Any

190 (94)

97 (48)

99 (97)

30 (29)

Blood and Lymphatic System Disorders

60 (30)

34 (17)

9 (9)

3 (3)

Anemia NOS

39 (19)

16 (8)

7 (7)

2 (2)

Gastrointestinal

171 (85)

40 (20)

75 (74)

19 (19)

Diarrhea NOS

82 (41)

9 (5)

21 (21)

0 (0)

Nausea

66 (33)

2 (1)

23 (23)

3 (3)

Abdominal pain NOS

61 (30)

12 (6)

28 (29)

10 (10)

Vomiting NOS

50 (25)

3 (2)

18 (18)

3 (3)

Constipation

43 (21)

0 (0)

16 (16)

2 (2)

Stomatitis

33 (16)

1 (1)

2 (2)

0 (0)

Dyspepsia

30 (15)

1 (1)

6 (6)

0 (0)

Abdominal pain upper

22 (11)

3 (2)

8 (8)

0 (0)

Metabolism and Nutritional Disorders

81 (40)

15 (8)

26 (26)

1 (1)

Anorexia

62 (31)

1 (1)

19 (19)

1 (1)

Musculoskeletal and Connective Tissue Disorders

90 (45)

11 (5)

35 (34)

5 (5)

Arthralgia

24 (12)

2 (1)

10 (10)

0 (0)

Back pain

21 (10)

1 (1)

13 (13)

3 (3)

General Disorders and Administration Site Conditions

147 (73)

27 (13)

65 (64)

7 (7)

Fatigue

84 (42)

15 (7)

37 (36)

4 (4)

Asthenia

44 (22)

10 (5)

10 (10)

2 (2)

Pyrexia

32 (16)

2 (1)

9 (9)

1(1)

Mucosal inflammation NOS

30 (15)

0 (0)

0 (0)

0 (0)

Nervous System Disorders

89 (44)

8 (4)

29 (28)

3 (3)

Dysgeusia

40 (20)

0 (0)

2 (2)

0 (0)

Headache

38 (19)

2 (1)

17 (17)

0 (0)

Psychiatric Disorders

36 (18)

1 (1)

15 (15)

1 (1)

Insomnia

24 (12)

0 (0)

10 (10)

1 (1)

Skin and Subcutaneous Tissue Disorders

125 (62)

12 (6)

31 (30)

0 (0)

Skin Discoloration

52 (26)

0 (0)

8 (8)

0 (0)

Rash NOS

30 (15)

2 (1)

6 (6)

0 (0)

PPE syndrome

28 (14)

9 (5)

2 (2)

0 (0)

Vascular Disorders

50 (25)

17 (8)

12 (12)

0 (0)

Hypertension NOS

28 (14)

8 (4)

7 (7)

0 (0)

Table 2 depicts common (≥ 10%) treatment-emergent laboratory abnormalities.

Table 2: Treatment-Emergent Laboratory Abnormalities in ≥ 10% of GIST Patients who Received SUTENT or Placebo in the Double-Blind Treatment Phase of Study A
*
Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
a
Grade 4 AEs in patients on SUTENT included alkaline phosphatase (1%), lipase (2%), creatinine (1%), hypokalemia (1%), neutropenia (2%), anemia (2%), and thrombocytopenia (1%).
b
Grade 4 AEs in patients on placebo included amylase (1%), lipase (1%), anemia (2%), and thrombocytopenia (1%).

Adverse Event, n (%)

SUTENT (n=202)

Placebo (n=102)

 

All Grades

Grade 3/4a

All Grades

Grade 3/4b

Any

 

68 (34)

 22 (22)
Gastrointestinal    
AST / ALT78 (39)3 (2)23 (23)1 (1)

Alkaline phosphatase

48 (24)

7 (4)

21 (21)

4 (4)

Total Bilirubin

32 (16)

2 (1)

8 (8)

0 (0)

Indirect Bilirubin

20 (10)

0 (0)

4 (4)

0 (0)

Amylase

35 (17)

10 (5)

12 (12)

3 (3)

Lipase

50 (25)

20 (10)

17 (17)

7 (7)

Cardiac    
Decreased LVEF22 (11)2 (1)3 (3)0 (0)
Renal / Metabolic    
Creatinine25 (12)1 (1)7 (7)0 (0)

Hypokalemia

24 (12)

1 (1)

4 (4)

0 (0)

Hypernatremia

20 (10)

0 (0)

4 (4)

1 (1)

Uric acid

31 (15)

16 (8)

16 (16)

8 (8)

Hematology    
Neutropenia107 (53)20 (10)4 (4)0 (0)

Lymphopenia

76 (38)

0 (0)

16 (16)

0 (0)

Anemia

52 (26)

6 (3)

22 (22)

2 (2)

Thrombocytopenia

76 (38)

10 (5)

4 (4)

0 (0)

Grade 3 or 4 treatment-emergent laboratory abnormalities were seen in 68 SUTENT patients (34%) versus 22 placebo patients (22%). Elevated liver function tests, pancreatic enzymes and creatinine were all more common in SUTENT patients than placebo patients. Decreased LVEF, myelosuppression and electrolyte disturbances were all more common in SUTENT patients than placebo patients. Treatment-emergent acquired hypothyroidism was noted in 4% of GIST patients on SUTENT versus 1% on placebo.

After a positive interim analysis, the study was unblinded, and patients on the placebo arm were given the opportunity to receive open-label SUTENT treatment [see CLINICAL TRIALS]. For 241 patients randomized to the SUTENT arm, including 139 who received SUTENT in both the double-blind and open-label treatment phases, the median duration of SUTENT treatment was 6 cycles (mean 8.5, range 1 – 44). For the 255 patients who ultimately received open-label SUTENT treatment, median duration of study treatment was 6 cycles (mean 7.8, range 1 – 37) from the time of the unblinding. A total of 118 patients (46%) required dosing interruptions, and a total of 72 patients (28%) required dose reductions during the open-label treatment phase. The incidence of treatment-emergent adverse reactions resulting in permanent discontinuation was 20%. The most common Grade 3 or 4 treatment-related adverse reactions experienced by patients receiving SUTENT in the open-label treatment phase were neutropenia (11%), fatigue (10%), hypertension (8%), asthenia (5%), diarrhea (5%), hand-foot syndrome (5%), nausea (4%), abdominal pain (3%), anorexia (3%), mucositis (2%), vomiting (2%), and hypothyroidism (2%).

Adverse Reactions in MRCC Patient Population

Treatment-Naive
The as-treated patient population for the interim safety analysis of the Phase 3 MRCC study included 735 patients, 375 randomized to SUTENT and 360 randomized to IFN-a. The median duration of treatment was 11.1 months (range: 0.4 – 46.1) for SUTENT treatment and 4.1 months (range: 0.1 – 45.6) for IFN-α treatment. Dose interruptions occurred in 202 patients (54%) on SUTENT and 141 patients (39%) on IFN-α. Dose reductions occurred in 194 patients (52%) on SUTENT and 98 patients (27%) on IFN-α. Discontinuation rates due to adverse reactions were 20% for SUTENT and 23% for IFN-α. Most treatment-related adverse events in both study arms were Grade 1 or 2 in severity. Grade 3 or 4 treatment-related adverse events were reported in 69% and 38% of patients on SUTENT versus IFN-α, respectively. Common treatment-related adverse events of any grade for patients receiving SUTENT are fatigue, diarrhea, nausea, stomatitis, hypertension, hand-foot syndrome, ejection fraction decline. Table 3 compares the incidence of common (≥10%) treatment-related adverse events for patients receiving SUTENT versus those on IFN-α.

Table 3: Treatment-Related Adverse Events Reported in at Least 10% of Patients with Treatment-Naïve MRCC Who Received SUTENT or IFN-α
*
The following terms have been combined: abdominal pain and abdominal pain upper.
**
The following terms have been combined: rash, rash erythematous, exfoliative rash, rash follicular,rash macular, rash papular, rash pruritic, rash maculo-papular, rash psoriaform, and rash generalised.

Adverse Event, n (%)

SUTENT (n =375)

IFN-α (n =360)

 

All Grades
n (%)

Grade 3/4
n (%)

All Grades
n (%)

Grade 3/4
n (%)

Any adverse event

358 (95.5%)

258 (68.8%)

331 (91.9%)

139 ( 38.6%)

Blood and lymphatic system disorders    
Thrombocytopenia69 (18.4%)

33 (8.8%)

11 (3.1%)2 (0.6 %)

Neutropenia

70 (18.7%)

40 (10.7%)

31 (8.6%)

12 (3.3%)

Anemia

51 (13.6%)

19 (5.1%)

31 (8.6%)

7 (1.9%)

Leukopenia

40 (10.7%)

12 (3.2%)

14 (3.9%)

3 (0.8%)

Metabolism and nutrition disorders    
Anorexia129 (34.4%)7 (1.9%)101 (28.1%)6 (1.7%)

Decreased appetite

37 (9.9%)

1 (0.3%)

38 (10.6%)

0 (0%)

Nervous system disorders    
Dysgeusia175 (46.7%)1 (0.3%)52 (13.9%)0 (0%)

Headache

53 (14.1%)

2 (0.5%)

55 (15.3%)

0 (0%)

Vascular disorders    
Hypertension113 (30.1%)46 (12.3%)6 (1.7%)

1 (0. 3%)

Respiratory, thoracic and mediastinal disorders    
Epistaxis67 (17.9%)3 (0.8%)5 (1.4%)0 (0%)
Gastrointestinal disorders    
Diarrhea229 (61.1%)33 (8.8%)49 (13.6%)1 (0.3%)

Nausea

195 (52.0%)

17 (4.5%)

124 (34.4%)

4 (1.1%)

Dyspepsia

118 (31.5%)

7 (1.9%)

13 (3.6%)

0 (0%)

Stomatitis

110 (29.3%)

5 (1.3%)

10 (2.8%)

1 (0.3%)

Vomiting

117 (31.2%)

14 (3.7%)

41 (11.4%)

2 (0.6%)

Abdominal pain*

70 (18.7%)

7 (1.9%)

15 (4.2%)

0 (0%)

Dry mouth

45 (12.0%)

0 (0%)

24 (6.7%)

1 (0.3%)

Constipation

44 (11.7%)

1 (0.3%)

14 (3.9%)

0 (0.0%)

Flatulence

43 (11.5%)

0 (0.0%)

6 (1.6%)

0 (0.0%)

Skin and subcutaneous tissue disorders    
Rash**115 (30.7%)4 (1.1%)33 (9.2%)3 (0.8%)

Palmar-plantar erythrodysesthesia

108 (30.0%)

32 (8.5%)

2 (0.6%)

0 (0%)

syndrome

    

Dry skin

79 (21.1%)

1 (0.3%)

19 (5.3%)

0 (0%)

Skin discoloration

89 (23.7%)

1 (0.3%)

0 (0%)

0 (0%)

Hair color changes

75 (20.0%)

0 (0%)

1 (0.3%)

0 (0%)

Erythema

39 (10.4%)

2 (0.5%)

3 (0.8%)

0 (0%)

Musculoskeletal and connective tissue disorders    
Pain in extremity66 (17.6%)5 (1.3%)11 (3.1%)0 (0%)

Arthralgia

43 (11.5%)

1 (0.3%)

49 (13.6%)

0 (0%)

Myalgia

32 (8.5%)

1 (0.3%)

60 (16.7%)

2 (0.6%)

General disorders and administration site conditions    
Fatigue206 (54.9%)43 (11.5%)186 (51.7%)48 (13.3%)

Mucosal inflammation

98 (26.1%)

7 (1.9%)

6 (1.7%)

1 (0.3%)

Asthenia

76 (20.3%)

28 (7.5%)

67 (18.6%)

14 (3.9%)

Pyrexia

31 (8.3%)

3 (0.8%)

125 (34.7%)

1 (0.3%)

Chills

28 (7.5%)

2 (0.5%)

105 (29.2%)

0 (0%)

Investigations    
Ejection fraction decreased51 (13.6%)10 (2.7%)11 (3.1%)3 (0.8%)

Weight decreased

46 (12.3%)

1 (0.3%)

50 (13.9%)

1 (0.3%)

In the treatment-naive MRCC study, 75 (20%) versus 37 (10%) patients experienced treatment- emergent Grade 4 chemistry laboratory abnormalities on SUTENT versus IFN-a, respectively. The most common Grade 4 chemistry abnormalities were hyperuricemia (14% on SUTENT, 8% on IFN-α) and increased lipase (3% on SUTENT, 1% on IFN-α). The most common Grade 3 chemistry abnormalities observed on both arms were increased lipase (15% on SUTENT, 7% on IFN-α) and hypophosphatemia (6% on SUTENT, 6% on IFN-α). Other common Grade 3 laboratory abnormalities on SUTENT were hyponatremia (8%) and increased amylase (5%), and on IFN-α was hyperglycemia (6%). Hematologic laboratory abnormalities in the treatment-naïve MRCC patient population are presented in Table 4.

Grade 4 hematology laboratory abnormalities in the Phase 3 MRCC study include neutropenia (2% on SUTENT, 1% on IFN-α) and anemia (2% on SUTENT, <1% on IFN-α). Grade 3 hematology laboratory abnormalities included neutropenia (15% on SUTENT, 8% on IFN-α), lymphopenia (16% on SUTENT, 24% on IFN-α), thrombocytopenia (8% on SUTENT, 1% on IFN-α), leukopenia (8% on SUTENT, 2% on IFN-α) and anemia (6% on SUTENT, 5% on IFN-α).

Table 4. Treatment-Emergent Laboratory Abnormalities Reported in at Least 10% of Treatment-Naïve MRCC Patients Who Received SUTENT or IFN-α
*
Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0
a
Grade 4 laboratory abnormalities in patients on SUTENT included uric acid (14%), lipase (3%), neutrophils (2%), lymphocytes (2%), hemoglobin (2%), platelets (1%), amylase (1%), ALT (<1%), creatine kinase (<1%), creatinine (<1%), glucose increased (<1%), calcium decreased (<1%), phosphorous (<1%), potassium increased (<1%), and sodium decreased (<1%).
b
Grade 4 laboratory abnormalities in patients on IFN-α included uric acid (8%), lymphocytes (2%), lipase (1%), neutrophils (1%), amylase (<1%), calcium increased (<1%), glucose decreased (<1%), potassium increased (<1%) and hemoglobin (<1%).

Laboratory Parameter, n (%)

Treatment-Naïve RCC

SUTENT (n=375)

IFN-α (n=360)

All Grades*

Grade 3/4*a

All Grades*

Grade 3/4*b

Gastrointestinal    
AST211 (56)6 (2)136 (38)8 (2)

ALT

192 (51)

10 (3)

144 (40)

9 (2)

Lipase

211 (56)

69 (18)

165 (46)

29 (8)

Alkaline phosphatase

171 (46)

7 (2)

132 (37)

6 (2)

Amylase

130 (35)

22 (6)

114 (32)

12 (3)

Total bilirubin

75 (20)

3 (1)

8 (2)

0 (0)

Indirect bilirubin

49 (13)

4 (1)

3 (1)

0 (0)

Renal/Metabolic    
Creatinine262 (70)2 (<1)183 (51)1 (<1)

Creatine kinase

183 (49)

9 (2)

40 (11)

4 (1)

Uric acid

173 (46)

54 (14)

119 (33)

29 (8)

Calcium decreased

156 (42)

4 (1)

145 (40)

4 (1)

Phosphorus

116 (31)

22 (6)

87 (24)

23 (6)

Albumin

106 (28)

4 (1)

72 (20)

0 (0)

Glucose increased

86 (23)

21 (6)

55 (15)

22 (6)

Sodium decreased

75 (20)

31 (8)

55 (15)

13 (4)

Glucose decreased

65 (17)

0 (0)

43 (12)

1 (<1)

Potassium increased

61 (16)

13 (3)

61 (17)

15 (4)

Calcium increased

50 (13)

2 (<1)

35 (10)

5 (1)

Potassium decreased

49 (13)

3 (1)

7 (2)

1 (<1)

Sodium increased

48 (13)

0 (0)

38 (10)

0 (0)

Hematology    
Neutrophils289 (77)65 (17)178 (49)

31 (9)

Hemoglobin

298 (79)

29 (8)

250 (69)

18 (5)

Platelets

255 (68)

35 (9)

85 (24)

2 (1)

Lymphocytes

256 (68)

66 (18)

245 (68)

93 (26)

Leukocytes

293 (78)

29 (8)

202 (56)

8 (2)

Cytokine-Refractory MRCC
The data described below reflect exposure to SUTENT in 169 patients with cytokine-refractory MRCC enrolled in Studies 1 and 2. The median duration of treatment was 5.5 months (range: 23 days to 11.2 months) for Study 1 and 7.9 months (range: 6 days to 1.3 years) for Study 2. Dose interruptions occurred in 48 patients (45%) on Study 1 and 45 patients (71%) on Study 2; one or more dose reductions occurred in 23 patients (22%) on Study 1 and 22 patients (35%) on Study 2. Permanent discontinuation from the study due to treatment-related adverse events occurred in 7 patients (8%) on Study 1 and 6 patients (10%) on Study 2. Treatment-related Adverse events are presented by maximum severity grade for at least 10% of the MRCC patient population in Table 5. Treatment-related Adverse events were experienced by nearly all of the patients with MRCC. Fatigue; gastrointestinal disorders, such as nausea, diarrhea, stomatitis, dyspepsia, vomiting and constipation; dysgeusia; skin discoloration; anorexia and rash were the most common treatment-related adverse events (experienced by at least 20% of the patients). The relative frequency of the most common all-causality adverse events was similar to that of these treatment-related adverse events.

Table 5: Treatment-Related Adverse Events Reported in at Least 10% of Patients Treated with SUTENT in the Two Cytokine-Refractory MRCC Studies
Severity grading was consistent with Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
*1 patient (0.6%) was missing.
Abbreviations: n=number of subjects, MRCC=metastatic renal cell carcinoma

Adverse Event

All Grades
n (%)

Grade 3/4
n (%)

Any Treatment-Related AE Experienced by ≥10% Patients

166 ( 98.2)

91 ( 53.9)

Blood and Lymphatic System Disorders

57 ( 33.7)

30 ( 15.8)

Anemia

21 ( 12.4)

6 ( 3.6)

Leukopenia

24 ( 14.2)

10 ( 5.9)

Neutropenia

24 ( 14.2)

14 ( 8.3)

Thrombocytopenia

23 ( 13.6)

11 ( 6.5)

Eye disorders

17 (10.1)

0 (0.0)

Gastrointestinal disorders

156 ( 92.3)

15 (8.9)

Constipation

34 ( 20.1)

0 ( 0.0)

Diarrhoea

83 ( 49.1)

5 ( 3.0)

Dyspepsia

69 ( 40.8)

1 ( 0.6)

Glossodynia

25 ( 14.8)

0 ( 0.0)

Nausea

84 ( 49.7)

2 ( 1.2)

Stomatitis

70 ( 41.4)

6 ( 3.6)

Vomiting

52 ( 30.8)

2 ( 1.2)

General disorders and administration site conditions

118 ( 69.8)

19 ( 11.2)

Fatigue

102 ( 60.4)

18 ( 10.7)

Mucosal inflammation

30 ( 17.8)

1 ( 0.6)

Infections and infestations

21 ( 12.4)

4 ( 2.4)

Investigations*

65 ( 38.5)

31 ( 20.1)

Ejection fraction decreased

24 ( 14.2)

4 ( 2.4)

Lipase increased

17 ( 10.1)

15 ( 8.9)

Metabolism and nutrition disorders

Anorexia

68 ( 40.2)

47 ( 27.8)

9 ( 5.3)

1 ( 0.6)

Musculoskeletal and connective tissue disorders

Pain in extremity

45 ( 26.6)

21 ( 12.4)

3 ( 1.8)

1 ( 0.6)

Nervous system disorders

101 ( 59.8)

6 ( 3.6)

Dysgeusia

71 ( 42.0)

0 ( 0.0)

Headache

25 ( 14.8)

1 ( 0.6)

Psychiatric disorders

17 ( 10.1)

2 ( 1.2)

Respiratory, thoracic and mediastinal disorders

40 ( 23.7)

3 ( 1.8)

Skin and subcutaneous tissue disorders

122 ( 72.2)

12 ( 7.1)

Dry skin

22 ( 13.0)

0 ( 0.0)

Erythema

20 ( 11.8)

0 ( 0.0)

Hair color changes

24 ( 14.2)

0 ( 0.0)

Palmar-plantar erythrodysesthesia syndrome

21 ( 12.4)

6 ( 3.6)

Rash

44 ( 26.0)

1 ( 0.6)

Skin discoloration

54 ( 32.0)

0 ( 0.0)

Vascular disorders

40 ( 23.7)

11 ( 6.5)

Hypertension

28 ( 16.6)

7 ( 4.1)

Treatment-emergent laboratory abnormalities are presented by maximum severity grade for at least 10% of the MRCC patient population in Table 6. Hematologic laboratory abnormalities in the MRCC patient population were comparable to that observed in the overall solid tumour patient population.

Table 6. Abnormal Post-Baseline Laboratory Tests Occurring in at Least 10% of Cytokine-Refractory MRCC Patients (As-Treated Population)
Grading is based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 criteria; the grading criteria are not available for all lab tests performed on study; if applicable, a subject was summarized only once for each test under the maximum post-baseline grade.
Abbreviations: n=number of subjects, MRCC=metastatic renal cell carcinoma
 

Total

50 mg QD, Schedule 4/2 (N=169)

Laboratory Test

Grade 1-4 n (%)

Grade 3/4 n (%)

Any

 

105 (62.1%)
Gastrointestinal  
Albumin(Hypoalbuminemia)47 ( 27.8)0 ( 0.0)

Alkaline Phosphatase

93 ( 55.0)

3 ( 1.8)

Amylase

47 ( 27.8)

8 ( 4.7)

AST/ALT

97 ( 57.4)

6 ( 3.6)

Lipase

84 ( 49.7)

28 ( 16.6)

Total Bilirubin

20 ( 11.8)

1 ( 0.6)

Renal/Metabolic  
Calcium (Hypercalcemia)19 ( 11.2)1 ( 0.6)
Calcium (Hypocalcemia)72 ( 42.6)1 ( 0.6)
Creatine Kinase65 ( 38.5)2 ( 1.2)
Creatinine100 ( 59.2)2 ( 1.2)
Glucose (Hyperglycemia)30 ( 17.8)6 ( 3.6)
Glucose (Hypoglycemia)34 ( 20.1)0 ( 0.0)
Hypophosphatemia37 ( 21.9)15 ( 8.9)
Potassium (Hyperkalemia)

23 ( 13.6)

7 ( 4.1)
Sodium (Hypernatremia)22 ( 13.0)1 ( 0.6)
Sodium (Hyponatremia)17 ( 10.1)6 ( 3.6)
Uric Acid83 ( 49.1)25 ( 14.8)
Hematology  
Anemia125 ( 74.0)12 ( 7.1)

Neutropenia

116 ( 68.6)

22 ( 13.0)

Lymphopenia

99 ( 58.6)

33 ( 19.5)

Thrombocytopenia

99 ( 58.6)

5 ( 3.0)

Adverse Reactions in the Phase 3 pancreatic NET Study

The median number of days on treatment was 139 days (range 13-532 days) for patients on SUTENT and 113 days (range 1-614 days) for patients on placebo. Nineteen patients (23%) on SUTENT and 3 patients (4%) on placebo were on study for >1 year. Dose interruptions occurred in 25 patients (30%) on SUTENT and 10 patients (12%) on placebo. Dose reductions occurred in 26 patients (31%) on SUTENT and 9 patients (11%) on placebo. Discontinuation rates due to treatment-related adverse reactions were 12% for SUTENT and 2% for placebo.

Most treatment-related adverse reactions in both study arms were Grade 1 or 2 in severity. Grade 3 or 4 treatment-related adverse reactions were reported in 43% versus 20% of patients on SUTENT versus placebo, respectively. Table 7 compares the incidence of common (≥10%) treatment-related adverse reactions for patients receiving SUTENT and reported more commonly in patients receiving SUTENT than in patients receiving placebo.

Table 7 – Treatment-Related Adverse Reactions Reported in the Phase 3 pancreatic NET Study in at Least 10% of Patients who Received SUTENT and More Commonly Than in Patients Given Placebo
Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

Adverse reactions

Pancreatic NET

SUTENT (n=83)              

Placebo (n=82)              

All Grades
n (%)             

Grade 3/4
n (%)            

All Grades
n (%)             

Grade 3/4
n (%)          

Any

81 (97.6%)

36 (43.4%)

64 (78.0%)

16 (19.5)

Blood and lymphatic system disorders    
Neutropoenia24 (28.9%)10 (12.0%)3 (3.7%)0 (0.0%)

Thrombocytopoenia

14 (16.9%)

3 (3.6%)

4 (4.9%)

0 (0.0%)

Metabolism and nutrition disorders    
Anorexia17 (20.5%)2 (2.4%)11 (13.4%)0 (0.0%)
Nervous system disorders    
Dysgeusia16 (19.3%)0 (0.0%)3 (3.7%)0 (0.0%)

Headeache

10 (12.0%)

0 (0.0%)

5 (6.1%)

1 (1.2%)

Vascular disorders    
Hypertension19 (22.9%)8 (9.6%)3 (3.7%)0 (0.0%)
Respiratory, thoracic and mediastinal
disorders
    
Epistaxis16 (19.3%)1 (1.2%)2 (2.4%)0 (0.0%)
Gastrointestinal disorders    
Diarrhoea44 (53.0%)4 (4.8%)25 (30.5%)1 (1.2%)

Nausea

32 (38.6%)

1 (1.2%)

18 (22.0%)

0 (0.0%)

Vomiting

21 (25.3%)

0 (0.0%)

14 (17.1%)

0 (0.0%)

Stomatitis

18 (21.7%)

3 (3.6%)

2 (2.4%)

0 (0.0%)

Abdominal pain

12 (14.5%)

1 (1.2%)

10 (12.2%)

3 (3.7%)

Dyspepsia

12 (14.5%)

0 (0.0%)

1 (1.2%)

0 (0.0%)

Skin and subcutaneous tissue disorders    
Hair colour changes24 (28.9%)1 (1.2%)1 (1.2%)0 (0.0%)

Palmar-plantar erythrodysaesthesia

19 (22.9%)

5 (6.0%)

2 (2.4%)

0 (0.0%)

syndrome

    

Rash

13 (15.7%)

0 (0.0%)

4 (4.9%)

0 (0.0%)

Dry skin

11 (13.3%)

0 (0.0%)

9 (11.0%)

0 (0.0%)

General disorders and administration
site conditions
    
Asthenia26 (31.3%)3 (3.6%)18 (22.0%)2 (2.4%)

Fatigue

24 (28.9%)

4 (4.8%)

14 (17.1%)

3 (3.7%)

Mucosal Inflammation

13 (15.7%)

1 (1.2%)

6 (7.3%)

0 (0.0%)

Investigations    
Weight decreased11 (13.3%)1 (1.2%)6 (7.3%)0 (0.0%)

Table 8 provides common (≥10%) treatment-emergent laboratory abnormalities.

Table 8. Laboratory Abnormalities Reported in the Phase 3 pancreatic NET Study in at Least 10% of Patients Who Received SUTENT
*
Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0
a
Grade 4 laboratory abnormalities in patients on SUTENT included creatinine (4%), lipase (4%), glucose decreased (2%), glucose increased (2%), neutrophils (2%), ALT (1%), AST (1%), platelets (1%), potassium increased (1%) and total bilirubin (1%).
b
Grade 4 laboratory abnormalities in patients on placebo included creatinine (3%), alkaline phosphatase (1%), glucose increased (1%) and lipase (1%).

Laboratory Parameter, n (%)

Pancreatic NET

SUTENT

Placebo

N

All Grades*

Grade 3/4*a

N

All Grades*

Grade 3/4*b

Gastrointestinal      
AST8259 (72)4 (5)8056 (70)2 (3)

ALT

82

50 (61)

3 (4)

80

44 (55)

2 (3)

Alkaline phosphatase

82

52 (63)

8 (10)

80

56 (70)

9 (11)

Total bilirubin

82

30 (37)

1 (1)

80

22 (28)

3 (4)

Amylase

74

15 (20)

3 (4)

74

7 (10)

1 (1)

Lipase

75

13 (17)

4 (5)

72

8 (11)

3 (4)

Renal/Metabolic      
Glucose increased8258 (71)

10 (12)

8062 (78)14 (18)

Albumin

81

33 (41)

1 (1)

79

29 (37)

1 (1)

Phosphorus

81

29 (36)

6 (7)

77

17 (22)

4 (5)

Calcium decreased

82

28 (34)

0 (0)

80

15 (19)

0 (0)

Sodium decreased

82

24 (29)

2 (2)

80

27 (34)

2 (3)

Creatinine

82

22 (27)

4 (5)

80

22 (28)

4 (5)

Glucose decreased

82

18 (22)

2 (2)

80

12 (15)

3 (4)

Potassium decreased

82

17 (21)

3 (4)

80

11 (14)

0 (0)

Magnesium decreased

52

10 (19)

0 (0)

39

4 (10)

0 (0)

Potassium increased

82

15 (18)

1 (1)

80

9 (11)

1 (1)

Hematology      
Neutrophils8258 (71)13 (16)8013 (16)0 (0)

Hemoglobin

82

53 (65)

0 (0)

80

44 (55)

1 (1)

Platelets

82

49 (60)

4 (5)

80

12 (15)

0 (0)

Lymphocytes

82

46 (56)

6 (7)

80

28 (35)

3 (4)

Other Adverse Reactions

Musculoskeletal

Rhabdomyolysis has been reported in some cases from non-pivotal clinical trials (see See WARNINGS AND PRECAUTIONS section and ADVERSE REACTIONS, Post-Market Adverse Drug Reactions).

Cardiovascular

See WARNINGS AND PRECAUTIONS section.

Investigations

Increase in blood uric acid.

Pulmonary Embolism

See WARNINGS AND PRECAUTIONS section.

Pancreatic and Hepatic Function

If symptoms of pancreatitis or hepatic failure are present, patients should have SUTENT discontinued. Pancreatitis was observed in 5 (1%) patients receiving SUTENT for treatment-naïve RCC compared to 1 (<1%) patient receiving IFN-α. Hepatotoxicity was observed in patients receiving SUTENT (See WARNINGS AND PRECAUTIONS section).

Seizures

See WARNINGS AND PRECAUTIONS section.

Skin and subcutaneous tissue disorders

Rare cases of Stevens-Johnson syndrome.

Post-Market Adverse Drug Reactions

The following adverse reactions have been identified during post approval use of SUTENT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Arterial Thromboembolic Events:

Cases of arterial thromboembolic events (ATE), sometimes fatal, have been reported in patients treated with sunitinib. The most frequent events included cerebrovascular accident, transient ischaemic attack and cerebral infarction. Risk factors associated with ATE, in addition to the underlying malignant disease and age ≥ 65 years, included hypertension, diabetes mellitus, and prior thromboembolic disease.

Cases of myocardial ischemia and myocardial infarction, some of which were fatal, have been reported.

Blood and lymphatic system disorders:

Cases of DIC, ITP, hemolytic anemia, and microangiopathic hemolytic anemia have been reported. Suspension of sunitinib is recommended. There are no data to support re-initiation of treatment following resolution. Physician discretion is recommended.

Cardiovascular:

Cases of left ventricular failure, cardiac failure, cardiovascular ischemia-related events (See Post- Market Adverse Drug Reactions- Arterial Thromboembolic Events) and rhythm disorder events have been reported in patients with pre-existing disease and/or cardiovascular risk factors, but a causal association with sunitinib could not be ruled out.

Cases of cardiomyopathy, in some cases with fatal outcome attributed to SUTENT, have been reported.

Thrombotic microangiopathy (TMA) (including cases identified as thrombotic thrombocytopenic purpura [TTP] and haemolytic uraemic syndrome [HUS]), sometimes leading to renal failure or a fatal outcome, has been reported. Permanently discontinue SUTENT in patients developing TMA.

Endocrine disorders:

Cases of thyroiditis and hypothyroidism, as well as hyperthyroidism, with some cases followed by hypothyroidism, have been reported in clinical trials and through post-marketing experience (See WARNINGS AND PRECAUTIONS, Thyroid Dysfunction).

Decreases in blood glucose, in some cases clinically symptomatic with serious outcomes, have been reported during sunitinib treatment in both diabetic and non-diabetic patients.

Hemorrhage:

Epistaxis is one of the most common hemorrhagic adverse events reported with sunitinib (see WARNINGS AND PRECAUTIONS, Hemorrhage). Although most cases are mild and self- limited, serious cases have been reported through post-marketing experience.

Hemorrhagic events reported through post-marketing experience, some of which were fatal, have included GI, respiratory, tumour, urinary tract and brain hemorrhages. In addition, cases of fatal hemorrhage associated with thrombocytopenia have been reported.

Cases of pulmonary, gastrointestinal, tumour, urinary tract, and brain hemorrhage, some fatal, have been reported in patients treated with SUTENT.

Hepatic and Biliary Function

Hepatotoxicity has been observed in clinical trials and post-marketing experience

Cases of cholecystitis, including acalculous cholecystitis and emphysematous cholecystitis, have been reported in patients treated with sunitinib (with fatal outcome in some cases).

Immune system disorders:

Hypersensitivity reactions, including angioedema, have been reported.

Infections and infestations:

Cases of serious infection (with or without neutropenia), in some cases with fatal outcome, have been reported. The infections observed most commonly with sunitinib treatment are respiratory infections (e.g. pneumonia, bronchitis), urinary tract infections, skin infections (e.g. cellulitis), sepsis/septic shock, and abscess (e.g. genital, anorectal, skin, limb, visceral), viral (e.g. nasopharyngitis, oral herpes), or fungal (e.g. candidiasis: oral, esophageal). Cases of necrotizing fasciitis, including of the perineum, sometimes fatal, have been reported.

Musculoskeletal and connective tissue disorders:

Cases of myopathy and/or rhabdomyolysis, some with acute renal failure and including fatality, have been reported. Most of these patients had pre-existing risk factors and/or were receiving concomitant medications known to be associated with these adverse reactions. Patients with signs or symptoms of muscle toxicity should be managed as per standard medical practice. (See WARNINGS AND PRECAUTIONS section)

Cases of osteonecrosis of the jaw (ONJ) have been reported in patients treated with sunitinib, most of which occurred in patients who had identified risk factors for ONJ, in particular exposure to i.v. bisphosphonates and/or a history of dental disease requiring invasive dental procedures (See WARNINGS AND PRECAUTIONS section).

Nervous system disorders:

Taste disturbance, including ageusia, has been reported.

Renal and urinary disorders:

Cases of renal impairment and/or failure, in some cases with fatal outcome, have been reported.

Cases of proteinuria and nephrotic syndrome have been reported (See WARNINGS AND PRECAUTIONS section). Baseline urinalysis is recommended, and patients should be monitored for the development or worsening of proteinuria. The safety of continued sunitinib treatment in patients with moderate to severe proteinuria has not been systematically evaluated. Discontinue sunitinib in patients with nephrotic syndrome.

Respiratory disorders:

Cases of pulmonary embolism, in some cases with fatal outcome attributed to SUTENT, have been reported. Cases of Pleural effusion, in some cases with fatal outcome, have been reported.

Vascular disorders:

Artery dissection and artery aneurysm (including rupture) have been reported in association with VEGFR TKIs, including SUTENT.

Gastrointestinal disorders:

Esophagitis.

Neurologic

Cases of reversible posterior leukoencephalopathy syndrome, in some cases with fatal outcome have been reported.

Other:

Fistula formation: Cases of fistula formation (including anal, enterocutaneous, gastrointestinal, tracheo-esophageal, and pleural fistulae), sometimes associated with tumour necrosis and/or regression, in some cases with fatal outcome, have been reported.

Skin and subcutaneous tissue disorders: Radiation interaction skin reaction has been reported when SUTENT was given concurrently with radiotherapy.

Cases of pyoderma gangrenosum, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including life-threatening and fatal cases, as well as erythema multiforme have been reported.

Tumour Lysis Syndrome: Cases of tumour lysis syndrome, some fatal and some occurring soon after initiation of SUTENT have been reported.

What's New

No Current Announcements.

Contact Pfizer Medical Information

Report an Adverse Event
1 866 723-7111