Non-Interventional Study (NIS) In Patients With Advanced And/Or Metastatic Renal Cell Carcinoma (mRCC) Treated With SUTENT®

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00684645
• Collaborator: (none)
• Enrollment: 186
• Locations: 21
• Duration (Months): 34
• Patients Per Site: 8.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Primary objective: to increase knowledge about safety, tolerability, quality of life and efficacy under conditions of routine use of SUTENT®. Secondary objectives: treatment response, hypothyroidism prevalence.The efficacy will be assessed using the Objective Response Rate, Time to Progression based on the RECIST criteria and the ECOG performance data.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma	Drug: SUTENT

Detailed Description

180 patients will be enrolled at 20 key oncological centres, the sample size is sufficient for exploratory analysis.

Study Design

• Study Type: Observational
• Actual Enrollment: 186 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Non-Interventional Study In Patients With Advanced And/Or Metastatic Renal Cell Carcinoma (mRCC) Treated With SUTENT®
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Patients treated with SUTENT® Patients with metastatic or advanced renal cell carcinoma after failure of cytokines therapy.	Drug: SUTENT; SUTENT® hard gelatin capsules containing 12.5 mg, 25 mg or 50 mg equivalent of sunitinib malate; daily dosage of 50 mg for 4 consecutive weeks followed by a 2-week rest period. Sutent is administered until disease progression or occurrence of unacceptable toxicity.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Objective Response [12 months]

   Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR). CR is defined as the disappearance of all target lesions. PR is defined as at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

2. Progression-free Survival (PFS) [Baseline to measured progressive disease (up to 12 months)]

   The period from study entry until disease progression, death, or date of last contact.

3. Overall Survival (OS) [Baseline to date of death (up to 12 months)]

   OS is the duration from enrollment to death.

4. Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Week 6 [Week 6]

   Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants in "Not reported" category were on study, had no data for this time point.

5. Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Month 3 [Month 3]

   Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants in "Not reported" category were on study, had no data for this time point.

6. Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Month 6 [Month 6]

   Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants in "Not reported" category were on study, had no data for this time point.

7. Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Month 9 [Month 9]

   Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants in "Not reported" category were on study, had no data for this time point.

8. Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Month 12 [Month 12]

   Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants in "Not reported" category were on study, had no data for this time point.

9. Correlation Between Sunitinib-induced Hypertension and Tumor Response to Treatment (PFS) [Baseline to date of first documentation of response to treatment (up to 12 months)]

   Sunitinib-induced hypertension was determined using blood pressure recorded at each postbaseline visit. Once participants were identified as having sunitinib-induced hypertension, they retained that status at subsequent visits. PFS is the time from start of study treatment to first documentation of tumor response to treatment. Hazard ratio represents the relationship between sunitinib-induced hypertension and PFS (presence/absence of hypertension).

10. Correlation Between Sunitinib-induced Hypertension and Tumor Response to Treatment (OS) [Baseline to date of death (up to 12 months)]

    Sunitinib-induced hypertension was determined using blood pressure recorded at each postbaseline visit. Once participants were identified as having sunitinib-induced hypertension, they retained that status at subsequent visits. OS is the time from start of study treatment to death. Hazard ratio represents the relationship between sunitinib-induced hypertension and OS.

11. Percentage of Participants With Hypothyroidism [Baseline, Months 3, 6, 9, 12]

    TSH and FT4 levels were measured and hypothyroidism was defined as a TSH level >5.0 mIU/L at that time point.

12. Percentage of Participants With Hypertension [Baseline, Week 6, Months 3, 6, 9, 12]

    Hypertension was defined as follows. Grade 1: Asymptomatic, transient (less than [<]24 hours) increase by >20mm Hg (diastolic) or to >150/100 mm Hg if previously within normal limits (WNL). Grade 2: Recurrent or persistent (24 hours or more) or symptomatic increase by >20 mm Hg (diastolic) or to >150/100 mm Hg if previously WNL. Grade 3: Requiring >1 drug or more intensive therapy than previously. Grade 4: Life-threatening. Grade 5: Death.

Other Outcome Measures

1. Summary of Adverse Events for Participants Who Required Dose Modification [Baseline up to 12 months]

   Adverse events (AEs) or treatment-emergent adverse events (TEAEs) were defined as newly occurring or worsening after first dose. Study drug modifications included reduced dose or temporary discontinuation of treatment.

2. Percentage of Participants With Treatment-emergent Hypertension, by Common Terminology Criteria for Adverse Events (CTCAE) Grade [Baseline up to 12 months]

   Sunitinib-induced hypertension: not present at baseline but developed through the study, or if present at baseline increased by more than (>) 20% during the study. Grade 1: Asymptomatic, transient (less than [<]24 hours) increase by >20 millimeters of Mercury (mm Hg) (diastolic) or to >150/100 mm Hg if previously within normal limits (WNL); Grade 2: Recurrent or persistent (>=24 hours) or symptomatic increase by >20 mm Hg (diastolic) or to >150/100 mm Hg if previously WNL; Grade 3: Requiring >1 drug or more intensive therapy than previously; Grade 4: Life-threatening; Grade 5: Death.

3. Percentage of Participants Responding to Treatment [12 months]

   Response categories for target lesions: Complete response (CR): Disappearance of all target lesions; Partial response (PR): At least a 30% decrease in the sum of the longest dimensions, reference=baseline sum of longest dimensions; Progressive disease (PD): At least a 20% increase in the sum of the longest dimensions, or the appearance of 1 or more new lesions; Stable disease (SD): Not sufficient shrinkage to qualify for PR, not sufficient increase to qualify for PD; Reference for PD and SD: smallest sum of longest dimensions since treatment started.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with advanced or metastatic renal cell carcinoma.

Exclusion Criteria:

• No previous cytokines therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Brno		Czech Republic	625 00
2	Pfizer Investigational Site	Brno		Czech Republic	656 53
3	Pfizer Investigational Site	Brno		Czech Republic	656 91
4	Pfizer Investigational Site	Ceske Budejovice		Czech Republic	370 87
5	Pfizer Investigational Site	Chomutov		Czech Republic	430 12
6	Pfizer Investigational Site	Hradec kralove		Czech Republic	500 05
7	Pfizer Investigational Site	Jihlava		Czech Republic	586 33
8	Pfizer Investigational Site	Karvina		Czech Republic	735 06
9	Pfizer Investigational Site	Liberec		Czech Republic	460 63
10	Pfizer Investigational Site	Nova Ves pod Plesi		Czech Republic	26204
11	Pfizer Investigational Site	Novy Jicin		Czech Republic	741 01
12	Pfizer Investigational Site	Ostrava		Czech Republic	703 84
13	Pfizer Investigational Site	Ostrava		Czech Republic	708 52
14	Pfizer Investigational Site	Pardubice		Czech Republic	532 03
15	Pfizer Investigational Site	Plzen		Czech Republic	301 00
16	Pfizer Investigational Site	Praha 5		Czech Republic	150 00
17	Pfizer Investigational Site	Praha		Czech Republic	100 34
18	Pfizer Investigational Site	Praha		Czech Republic	128 08
19	Pfizer Investigational Site	Praha		Czech Republic	140 59
20	Pfizer Investigational Site	Praha		Czech Republic	150 00
21	Pfizer Investigational Site	Zlin		Czech Republic	639 00

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00684645
• Other Study ID Numbers: A6181171
• First Posted: May 26, 2008
• Last Update Posted: Aug 21, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by Pfizer: Safety and tolerability of SUTENT® in patients with metastatic or advanced renal cell carcinoma after failure of cytokines in real-life setting.
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Period Title: Overall Study
STARTED	186
COMPLETED	72
NOT COMPLETED	114

Baseline Characteristics

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Overall Participants	186
Age, Customized (participants) [Number]
18 to 44 years	10 5.4%
45 to 64 years	99 53.2%
65 years or more	77 41.4%
Sex: Female, Male (Count of Participants)
Female	58 31.2%
Male	128 68.8%
Involvement of Regional Lymph Nodes (participants) [Number]
Iliac	31 16.7%
Paraaortal	25 13.4%
Paracaval	6 3.2%
Previous Anti-Tumor Therapy (participants) [Number]
Prior Radiotherapy	152 81.7%
Prior Chemotherapy	173 93%
Prior Hormonal Therapy	180 96.8%
Prior Immunotherapy	35 18.8%
Prior Cancer Surgeries	8 4.3%
Eastern Cooperative Oncology Group (ECOG) Performance Status (percentage of participants) [Number]
ECOG Performance Status 0	23 12.4%
ECOG Performance Status 1	72 38.7%
ECOG Performance Status 2	5 2.7%
ECOG Performance Status 3	0 0%
ECOG Performance Status 4	0 0%
ECOG Performance Status 5	0 0%
Frequency of Involved Disease Sites (participants) [Number]
Adrenal	5 2.7%
Bone	32 17.2%
Chest wall	1 0.5%
Kidney	26 14%
Liver	20 10.8%
Lung	88 47.3%
Lymph node	7 3.8%
Lymph node - Mediastinum	13 7%
Lymph node - Other	4 2.2%
Lymph node - Retroperitoneal	12 6.5%
Lymph node - Supraclavicular	2 1.1%
Lymph node - Regional	2 1.1%
Mediastinum	3 1.6%
Other	13 7%
Pancreas	4 2.2%
Pelvis	1 0.5%
Peritoneum	7 3.8%
Pleura	1 0.5%
Skin	1 0.5%
Spleen	1 0.5%
Prevalence of hypothyroidism (participants) [Number]
Hypothyroidism present	15 8.1%
Hypothyroidism absent	171 91.9%
Prevalence of Hypertension (participants) [Number]
Hypertension present	119 64%
Hypertension absent	67 36%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Objective Response
Description	Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR). CR is defined as the disappearance of all target lesions. PR is defined as at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): all participants who received at least one dose of the study medication.

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
Number (95% Confidence Interval) [percentage of participants]	25.3 13.6%

2. Primary Outcome

Title	Progression-free Survival (PFS)
Description	The period from study entry until disease progression, death, or date of last contact.
Time Frame	Baseline to measured progressive disease (up to 12 months)

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
Median (95% Confidence Interval) [months]	9.8

3. Primary Outcome

Title	Overall Survival (OS)
Description	OS is the duration from enrollment to death.
Time Frame	Baseline to date of death (up to 12 months)

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
Median (95% Confidence Interval) [months]	NA

4. Primary Outcome

Title	Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Week 6
Description	Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants in "Not reported" category were on study, had no data for this time point.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

FAS. Percentages based on entire FAS population.

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
ECOG Grade 0	18.8 10.1%
ECOG Grade 1	68.3 36.7%
ECOG Grade 2	8.6 4.6%
ECOG Grade 3	2.2 1.2%
ECOG Grade 4	0.0 0%
ECOG Grade 5	0.0 0%
Not Reported	2.2 1.2%

5. Primary Outcome

Title	Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Month 3
Description	Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants in "Not reported" category were on study, had no data for this time point.
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

FAS. Percentages based on entire FAS population.

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
ECOG Grade 0	16.7 9%
ECOG Grade 1	60.2 32.4%
ECOG Grade 2	10.2 5.5%
ECOG Grade 3	2.7 1.5%
ECOG Grade 4	0.0 0%
ECOG Grade 5	0.0 0%
Not Reported	10.2 5.5%

6. Primary Outcome

Title	Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Month 6
Description	Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants in "Not reported" category were on study, had no data for this time point.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

FAS. Percentages based on entire FAS population.

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
ECOG Grade 0	14.5 7.8%
ECOG Grade 1	47.8 25.7%
ECOG Grade 2	4.3 2.3%
ECOG Grade 3	1.6 0.9%
ECOG Grade 4	1.1 0.6%
ECOG Grade 5	0.0 0%
Not Reported	30.6 16.5%

7. Primary Outcome

Title	Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Month 9
Description	Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants in "Not reported" category were on study, had no data for this time point.
Time Frame	Month 9

Outcome Measure Data

Analysis Population Description

FAS. Percentages based on entire FAS population.

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
ECOG Grade 0	11.8 6.3%
ECOG Grade 1	36.6 19.7%
ECOG Grade 2	4.8 2.6%
ECOG Grade 3	0.5 0.3%
ECOG Grade 4	0.0 0%
ECOG Grade 5	0.0 0%
Not Reported	46.2 24.8%

8. Primary Outcome

Title	Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Month 12
Description	Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair. 5: Dead. Participants in "Not reported" category were on study, had no data for this time point.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

FAS. Percentages based on entire FAS population.

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
ECOG Grade 0	15.1 8.1%
ECOG Grade 1	39.8 21.4%
ECOG Grade 2	8.1 4.4%
ECOG Grade 3	4.8 2.6%
ECOG Grade 4	0.5 0.3%
ECOG Grade 5	1.1 0.6%
Not Reported	30.6 16.5%

9. Primary Outcome

Title	Correlation Between Sunitinib-induced Hypertension and Tumor Response to Treatment (PFS)
Description	Sunitinib-induced hypertension was determined using blood pressure recorded at each postbaseline visit. Once participants were identified as having sunitinib-induced hypertension, they retained that status at subsequent visits. PFS is the time from start of study treatment to first documentation of tumor response to treatment. Hazard ratio represents the relationship between sunitinib-induced hypertension and PFS (presence/absence of hypertension).
Time Frame	Baseline to date of first documentation of response to treatment (up to 12 months)

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
Sunitinib-induced hypertension starting at Week 6	39 21%
Sunitinib-induced hypertension starting at Month 3	16 8.6%
Sunitinib-induced hypertension starting at Month 6	11 5.9%
Sunitinib-induced hypertension starting at Month 9	12 6.5%
Sunitinib-induced hypertension starting Month 12	4 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib
	Comments	Time to PFS was analyzed using survival analysis methodology. Model was fitted with sunitinib-induced hypertension included as a time-dependent covariate (presence versus absence of hypertension).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cox proportional hazard
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.395
	Confidence Interval	(2-Sided) 95%; 0.257 to 0.609
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Primary Outcome

Title	Correlation Between Sunitinib-induced Hypertension and Tumor Response to Treatment (OS)
Description	Sunitinib-induced hypertension was determined using blood pressure recorded at each postbaseline visit. Once participants were identified as having sunitinib-induced hypertension, they retained that status at subsequent visits. OS is the time from start of study treatment to death. Hazard ratio represents the relationship between sunitinib-induced hypertension and OS.
Time Frame	Baseline to date of death (up to 12 months)

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
Sunitinib-induced hypertension starting at Week 6	39 21%
Sunitinib-induced hypertension starting at Month 3	16 8.6%
Sunitinib-induced hypertension starting at Month 6	11 5.9%
Sunitinib-induced hypertension starting at Month 9	12 6.5%
Sunitinib-induced hypertension starting Month 12	4 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib
	Comments	Time to OS was analyzed using survival analysis methodology. Model was fitted with sunitinib-induced hypertension included as a time-dependent covariate (presence versus absence of hypertension).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0221
	Comments
	Method	Cox proportional hazard
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.361
	Confidence Interval	(2-Sided) 95%; 0.151 to 0.864
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Primary Outcome

Title	Percentage of Participants With Hypothyroidism
Description	TSH and FT4 levels were measured and hypothyroidism was defined as a TSH level >5.0 mIU/L at that time point.
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS. n = number of participants with evaluable data at that time point.

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
Baseline (n=186)	8.1 4.4%
Month 3 (n=168)	17.9 9.6%
Month 6 (n=131)	18.3 9.8%
Month 9 (n=100)	20.0 10.8%
Month 12 (n=134)	20.9 11.2%

12. Primary Outcome

Title	Percentage of Participants With Hypertension
Description	Hypertension was defined as follows. Grade 1: Asymptomatic, transient (less than [<]24 hours) increase by >20mm Hg (diastolic) or to >150/100 mm Hg if previously within normal limits (WNL). Grade 2: Recurrent or persistent (24 hours or more) or symptomatic increase by >20 mm Hg (diastolic) or to >150/100 mm Hg if previously WNL. Grade 3: Requiring >1 drug or more intensive therapy than previously. Grade 4: Life-threatening. Grade 5: Death.
Time Frame	Baseline, Week 6, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description

FAS. n = number of participants with evaluable data at that time point.

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
Baseline (n=186)	64.0 34.4%
Week 6 (n=182)	51.1 27.5%
Month 3 (n=168)	48.8 26.2%
Month 6 (n=131)	54.2 29.1%
Month 9 (n=100)	54.0 29%
Month 12 (n=134)	39.6 21.3%

13. Other Pre-specified Outcome

Title	Summary of Adverse Events for Participants Who Required Dose Modification
Description	Adverse events (AEs) or treatment-emergent adverse events (TEAEs) were defined as newly occurring or worsening after first dose. Study drug modifications included reduced dose or temporary discontinuation of treatment.
Time Frame	Baseline up to 12 months

Outcome Measure Data

Analysis Population Description

Number of participants analyzed = All participants who required dose modification because of an adverse event. The total number of participants may exceed the number of participants analyzed because one participant may have reported more than one adverse event.

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	17
Anaemia	2 1.1%
Leukopenia	2 1.1%
Neutropenia	1 0.5%
Thrombocytopenia	6 3.2%
Hypothyroidism	1 0.5%
Aphthous stomatitis	1 0.5%
Stomatitis	2 1.1%
Disease progression	9 4.8%
Oedema peripheral	1 0.5%
Pyrexia	1 0.5%
Jaundice	1 0.5%
Bronchopneumonia	2 1.1%
Herpes dermatitis	1 0.5%
Urinary tract infection	2 1.1%
False positive investigation result	1 0.5%
Decreased appetite	2 1.1%
Osteonecrosis of jaw	1 0.5%
Leukaemia	1 0.5%
Renal cell carcinoma	2 1.1%
Cerebellar syndrome	1 0.5%
Cerebrovascular accident	1 0.5%
Loss of consciousness	1 0.5%
Haematuria	1 0.5%
Renal disorder	1 0.5%
Asthma	1 0.5%
Haemoptysis	1 0.5%
Pulmonary embolism	1 0.5%
Dermatitis exfoliative	1 0.5%
Palmar-plantar erythrodysaesthesia syndrome	3 1.6%
Rash	1 0.5%
Skin erosion	1 0.5%
Swelling face	1 0.5%
Deep vein thrombosis	1 0.5%
Hypertension	4 2.2%
Infarction	1 0.5%
Venous thrombosis limb	1 0.5%

14. Other Pre-specified Outcome

Title	Percentage of Participants With Treatment-emergent Hypertension, by Common Terminology Criteria for Adverse Events (CTCAE) Grade
Description	Sunitinib-induced hypertension: not present at baseline but developed through the study, or if present at baseline increased by more than (>) 20% during the study. Grade 1: Asymptomatic, transient (less than [<]24 hours) increase by >20 millimeters of Mercury (mm Hg) (diastolic) or to >150/100 mm Hg if previously within normal limits (WNL); Grade 2: Recurrent or persistent (>=24 hours) or symptomatic increase by >20 mm Hg (diastolic) or to >150/100 mm Hg if previously WNL; Grade 3: Requiring >1 drug or more intensive therapy than previously; Grade 4: Life-threatening; Grade 5: Death.
Time Frame	Baseline up to 12 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
Hypertension, Grade 1	3.2 1.7%
Hypertension, Grade 2	1.1 0.6%
Hypertension, Grade 3	0.5 0.3%

15. Other Pre-specified Outcome

Title	Percentage of Participants Responding to Treatment
Description	Response categories for target lesions: Complete response (CR): Disappearance of all target lesions; Partial response (PR): At least a 30% decrease in the sum of the longest dimensions, reference=baseline sum of longest dimensions; Progressive disease (PD): At least a 20% increase in the sum of the longest dimensions, or the appearance of 1 or more new lesions; Stable disease (SD): Not sufficient shrinkage to qualify for PR, not sufficient increase to qualify for PD; Reference for PD and SD: smallest sum of longest dimensions since treatment started.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
Measure Participants	186
Complete response	2.2 1.2%
Partial response	23.1 12.4%
Stable / No response	46.2 24.8%
Progressive disease	19.9 10.7%

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Sunitinib
Arm/Group Description	The use and dosage recommendations for Sunitinib (Sutent) were in accordance with the local Summary of Product Characteristics.
All Cause Mortality
	Sunitinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	31/186 (16.7%)
Blood and lymphatic system disorders
Anaemia	1/186 (0.5%)
Thrombocytopenia	4/186 (2.2%)
Cardiac disorders
Cardiac failure	1/186 (0.5%)
Endocrine disorders
Hypothyroidism	1/186 (0.5%)
Gastrointestinal disorders
Diverticulum intestinal	1/186 (0.5%)
Lower gastrointestinal haemorrhage	1/186 (0.5%)
Stomatitis	1/186 (0.5%)
General disorders
Disease progression	15/186 (8.1%)
Infections and infestations
Bronchopneumonia	1/186 (0.5%)
Empyema	1/186 (0.5%)
Injury, poisoning and procedural complications
Post procedural haemorrhage	1/186 (0.5%)
Investigations
Weight decreased	1/186 (0.5%)
Metabolism and nutrition disorders
Decreased appetite	1/186 (0.5%)
Dehydration	1/186 (0.5%)
Hypercalcaemia	1/186 (0.5%)
Hypochloraemia	1/186 (0.5%)
Hyponatraemia	1/186 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma	2/186 (1.1%)
Nervous system disorders
Cerebellar syndrome	1/186 (0.5%)
Cerebrovascular accident	1/186 (0.5%)
Loss of consciousness	1/186 (0.5%)
Renal and urinary disorders
Haematuria	1/186 (0.5%)
Renal disorder	1/186 (0.5%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/186 (0.5%)
Skin and subcutaneous tissue disorders
Dermatitis exfoliative	1/186 (0.5%)
Vascular disorders
Deep vein thrombosis	1/186 (0.5%)
Hypertension	1/186 (0.5%)
Infarction	1/186 (0.5%)
Other (Not Including Serious) Adverse Events
	Sunitinib
	Affected / at Risk (%)	# Events
Total	52/186 (28%)
Blood and lymphatic system disorders
Anaemia	3/186 (1.6%)
Leukopenia	3/186 (1.6%)
Neutropenia	2/186 (1.1%)
Thrombocytopenia	8/186 (4.3%)
Endocrine disorders
Hyperthyroidism	1/186 (0.5%)
Hypothyroidism	2/186 (1.1%)
Gastrointestinal disorders
Aphthous stomatitis	1/186 (0.5%)
Diarrhoea	3/186 (1.6%)
Duodenal ulcer	1/186 (0.5%)
Nausea	2/186 (1.1%)
Periodontitis	1/186 (0.5%)
Stomatitis	3/186 (1.6%)
General disorders
Adverse event	1/186 (0.5%)
Chest pain	1/186 (0.5%)
Disease progression	1/186 (0.5%)
Face oedema	1/186 (0.5%)
Fatigue	4/186 (2.2%)
Mucosal inflammation	2/186 (1.1%)
Oedema peripheral	2/186 (1.1%)
Pyrexia	2/186 (1.1%)
Hepatobiliary disorders
Jaundice	1/186 (0.5%)
Infections and infestations
Bronchopneumonia	1/186 (0.5%)
Herpes dermatitis	1/186 (0.5%)
Urinary tract infection	2/186 (1.1%)
Investigations
Alanine aminotransferase increased	1/186 (0.5%)
Aspartate aminotransferase increased	1/186 (0.5%)
Blood creatinine increased	1/186 (0.5%)
Blood parathyroid hormone increased	1/186 (0.5%)
Blood thyroid stimulating hormone increased	1/186 (0.5%)
False positive investigation result	1/186 (0.5%)
Weight decreased	2/186 (1.1%)
Metabolism and nutrition disorders
Cachexia	1/186 (0.5%)
Decreased appetite	4/186 (2.2%)
Dehydration	1/186 (0.5%)
Hyperuricaemia	1/186 (0.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/186 (0.5%)
Arthritis	1/186 (0.5%)
Osteonecrosis of jaw	1/186 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia	2/186 (1.1%)
Nervous system disorders
Paraesthesia	1/186 (0.5%)
Psychiatric disorders
Insomnia	1/186 (0.5%)
Renal and urinary disorders
Urinary retention	1/186 (0.5%)
Reproductive system and breast disorders
Erectile dysfunction	1/186 (0.5%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/186 (0.5%)
Epistaxis	3/186 (1.6%)
Haemoptysis	1/186 (0.5%)
Skin and subcutaneous tissue disorders
Dry skin	1/186 (0.5%)
Erythema	1/186 (0.5%)
Palmar-plantar erythrodysaesthesia syndrome	4/186 (2.2%)
Rash	4/186 (2.2%)
Skin disorder	1/186 (0.5%)
Skin erosion	1/186 (0.5%)
Skin toxicity	1/186 (0.5%)
Swelling face	1/186 (0.5%)
Vascular disorders
Hypertension	8/186 (4.3%)
Phlebitis	1/186 (0.5%)
Varicose vein	1/186 (0.5%)
Venous thrombosis limb	1/186 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.