Axitinib (AG 013736) As Second Line Therapy For Metastatic Renal Cell Cancer

• ClinicalTrials.gov Identifier: NCT00678392
• Recruitment Status: Completed
• First Posted: May 15, 2008
• Results First Posted: March 27, 2012
• Last Update Posted: January 9, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Kidney Neoplasms
• Interventions: Drug: Axitinib (AG-013736); Drug: Sorafenib
• Enrollment: 723

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Period Title: Overall Study
Started	361	362
Treated	359	355
Completed	0	0
Not Completed	361	362
Reason Not Completed
Adverse Event	0	6
Death	280	269
Lost to Follow-up	15	13
Objective Progression or Relapse	3	8
Sponsor's Decision	1	2
Withdrawal by Subject	4	4
Randomized But Not Treated	2	7
Other	56	53

Baseline Characteristics

Arm/Group Title		Axitinib 5 mg	Sorafenib 400 mg	Total
Arm/Group Description		Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		361	362	723
Baseline Analysis Population Description		Full analysis set (FAS) included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or receive a different drug from that to which they were randomized.
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	361 participants	362 participants	723 participants
Less than (<) 65 years		238	238	476
Greater than or equal to (>=) 65 years		123	124	247
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	361 participants	362 participants	723 participants
	Female	96 26.6%	104 28.7%	200 27.7%
	Male	265 73.4%	258 71.3%	523 72.3%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as the time in months from start of study treatment to the first documentation of objective tumor progression of disease (PD) or to death due to any cause, whichever occurs first. PD was assessed by response evaluation criteria in solid tumors (RECIST) version 1.0. PD: >=20 percent (%) increase in the sum of the longest dimensions (LD) of the target lesions taking as a reference the smallest sum of the LD recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. Occurrence of a pleural effusion or ascites was also considered PD if demonstrated by cytological investigation and it was not previously documented. New bone lesions not previously documented were considered PD if confirmed by computed tomography/magnetic resonance imaging or X-ray.
Time Frame	From initiation of treatment up to follow-up period (up to 3 years)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	361	362
Median (95% Confidence Interval); Unit of Measure: Months
	6.7; (6.3 to 8.6)	4.7; (4.6 to 5.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib 5 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value was obtained from 1-sided log rank test, stratified by eastern cooperative oncology group (ECOG) and prior treatment. One-sided log-rank test at 0.025 level of significance was used to compare PFS between the 2 treatment arms.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.665
	Confidence Interval	(2-Sided) 95%; 0.544 to 0.812
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the duration from start of study treatment to date of death due to any cause. OS was calculated as (months) = (date of death minus the date of first dose of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored on last date the participants were known to be alive.
Time Frame	From initiation of treatment up to follow-up period (up to 3 years)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	361	362
Median (95% Confidence Interval); Unit of Measure: Months
	20.1; (16.7 to 23.4)	19.2; (17.5 to 22.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib 5 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3744
	Comments	[Not Specified]
	Method	Log Rank
	Comments	P-value was obtained from a 1-sided log-rank test of treatment stratified by ECOG performance status and prior treatment.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.969
	Confidence Interval	(2-Sided) 95%; 0.800 to 1.174
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	ORR = percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0 recorded from first dose of study treatment until PD or death due to any cause. CR: disappearance of all target, non target lesions and no appearance of new lesions, documented on 2 occasions separated by at least 4 weeks. PR: at least 30 % decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non target lesions, no appearance of new lesions. PD: >=20% increase in sum of LD of the target lesions taking as a reference smallest sum of LD recorded since the start of treatment or unequivocal progression in non-target lesions or appearance of 1 or more new lesions. Occurrence of pleural effusion or ascites if demonstrated by cytological investigation, not previously documented. New bone lesions not previously documented if confirmed by computed tomography/magnetic resonance imaging or X-ray.
Time Frame	From initiation of treatment up to follow-up period (up to 3 years)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	361	362
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	19.4; (15.4 to 23.9)	9.4; (6.6 to 12.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Axitinib 5 mg, Sorafenib 400 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	P-value was obtained from a 1-sided Cochran-Mantel-Haenszel test of treatment stratified by ECOG performance status and prior treatment.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	2.056
	Confidence Interval	(2-Sided) 95%; 1.408 to 3.003
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Duration of Response (DR)
Description	DR: time from first documentation of objective tumor response (CR or PR), that was subsequently confirmed, to the first documentation of PD or to death due to any cause, whichever occurred first as per RECIST version 1.0, a) CR: disappearance of all target, non target lesions and no appearance of new lesions, documented on 2 occasions separated by at least 4 weeks, b) PR: at least 30 % decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non target lesions, no appearance of new lesions, c) PD: >=20% increase in sum of LD of the target lesions taking as a reference smallest sum of LD recorded since the start of treatment or unequivocal progression in non-target lesions or appearance of 1 or more new lesions. Occurrence of pleural effusion or ascites if demonstrated by cytological investigation, not previously documented. New bone lesions not previously documented if confirmed by computed tomography/magnetic resonance imaging or X-ray.
Time Frame	From initiation of treatment up to follow-up period (up to 3 years)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	361	362
Median (95% Confidence Interval); Unit of Measure: Months
	11.0 [1]; (7.4 to NA)	10.6; (8.8 to 11.5)

[1]

The upper limit of 95 percent confidence interval was not reached at the time of data cut-off.

5. Secondary Outcome

Title	Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life- threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs.
Time Frame	From initiation of treatment up to follow-up period (up to 3 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	359	355
Measure Type: Number; Unit of Measure: Percentage of participants
AEs	96.1	98.0
SAEs	40.7	35.8

6. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs) by Severity
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of the AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 1= mild; Grade 2= moderate; Grade 3= severe; Grade 4= life-threatening or disabling; Grade 5= death related to AE.
Time Frame	From initiation of treatment up to follow-up period (up to 3 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	359	355
Measure Type: Number; Unit of Measure: Percentage of participants
Grade 1	3.9	3.1
Grade 2	20.1	21.7
Grade 3	47.6	52.4
Grade 4	10.6	11.5
Grade 5	13.9	9.3

7. Secondary Outcome

Title	Percentage of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life -threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious and non -serious AEs.
Time Frame	From initiation of treatment up to follow-up period (up to 3 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	359	355
Measure Type: Number; Unit of Measure: Percentage of participants
AEs	92.2	95.2
SAEs	15.3	13.8

8. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities: Hematology
Description	Hematology laboratory test included hemoglobin, platelet count, white blood cells count, neutrophils and lymphocytes. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.
Time Frame	From initiation of treatment up to follow-up period (up to 3 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated according to actual study treatment received. Here, "n" signifies number of participants available for specified categories for each arm respectively.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	359	355
Measure Type: Number; Unit of Measure: Participants
Hemoglobin: Grade 1 (n =320, 316)	93	112
Hemoglobin: Grade 2 (n =320, 316)	19	41
Hemoglobin: Grade 3 (n =320, 316)	1	11
Hemoglobin: Grade 4 (n =320, 316)	0	1
Lymphocytes: Grade 1 (n =317, 309)	7	7
Lymphocytes: Grade 2 (n =317, 309)	89	93
Lymphocytes: Grade 3 (n =317, 309)	10	11
Lymphocytes: Grade 4 (n =317, 309)	0	0
Neutrophils: Grade 1 (n =316, 308)	13	20
Neutrophils: Grade 2 (n =316, 308)	4	4
Neutrophils: Grade 3 (n =316, 308)	2	2
Neutrophils: Grade 4 (n =316, 308)	0	0
Platelets: Grade 1 (n =312, 310)	47	41
Platelets: Grade 2 (n =312, 310)	0	3
Platelets: Grade 3 (n =312, 310)	1	0
Platelets: Grade 4 (n =312, 310)	0	0
White Blood Cells: Grade 1 (n =320, 315)	32	36
White Blood Cells: Grade 2 (n =320, 315)	4	12
White Blood Cells: Grade 3 (n =320, 315)	0	1
White Blood Cells: Grade 4 (n =320, 315)	0	0

9. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities: Biochemistry
Description	Biochemistry laboratory test included parameters: alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bicarbonate, bilirubin, creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, hypophosphatemia and lipase. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.
Time Frame	From initiation of treatment up to follow-up period (up to 3 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated according to actual study treatment received. Here, "n" signifies number of participants available for specified categories for each arm respectively.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	359	355
Measure Type: Number; Unit of Measure: Participants
Alanine aminotransferase: Grade 1 (n =331, 313)	65	57
Alanine aminotransferase: Grade 2 (n =331, 313)	8	6
Alanine aminotransferase: Grade 3 (n =331, 313)	1	2
Alanine aminotransferase: Grade 4 (n =331, 313)	0	3
Alkaline phosphatase: Grade 1 (n =336, 319)	88	92
Alkaline phosphatase: Grade 2 (n =336, 319)	8	15
Alkaline phosphatase: Grade 3 (n =336, 319)	4	3
Alkaline phosphatase: Grade 4 (n =336, 319)	0	0
Amylase: Grade 1 (n =338, 319)	64	76
Amylase: Grade 2 (n =338, 319)	12	21
Amylase: Grade 3 (n =338, 319)	7	6
Amylase: Grade 4 (n =338, 319)	0	1
Aspartate aminotransferase: Grade 1 (n =331, 311)	59	67
Aspartate aminotransferase: Grade 2 (n =331, 311)	5	7
Aspartate aminotransferase: Grade 3 (n =331, 311)	1	4
Aspartate aminotransferase: Grade 4 (n =331, 311)	0	0
Bicarbonate: Grade 1 (n =314, 291)	127	115
Bicarbonate: Grade 2 (n =314, 291)	11	10
Bicarbonate: Grade 3 (n =314, 291)	0	0
Bicarbonate: Grade 4 (n =314, 291)	1	0
Bilirubin: Grade 1 (n =336, 318)	16	12
Bilirubin: Grade 2 (n =336, 318)	8	2
Bilirubin: Grade 3 (n =336, 318)	1	1
Bilirubin: Grade 4 (n =336, 318)	0	0
Creatinine: Grade 1 (n =336, 318)	155	121
Creatinine: Grade 2 (n =336, 318)	30	9
Creatinine: Grade 3 (n =336, 318)	0	1
Creatinine: Grade 4 (n =336, 318)	0	0
Hypercalcemia: Grade 1 (n =336, 319)	92	22
Hypercalcemia: Grade 2 (n =336, 319)	8	1
Hypercalcemia: Grade 3 (n =336, 319)	1	0
Hypercalcemia: Grade 4 (n =336, 319)	0	0
Hyperglycemia: Grade 1 (n =336, 319)	41	28
Hyperglycemia: Grade 2 (n =336, 319)	45	37
Hyperglycemia: Grade 3 (n =336, 319)	7	7
Hyperglycemia: Grade 4 (n =336, 319)	0	0
Hyperkalemia: Grade 1 (n =333, 314)	0	0
Hyperkalemia: Grade 2 (n =333, 314)	42	22
Hyperkalemia: Grade 3 (n =333, 314)	9	8
Hyperkalemia: Grade 4 (n =333, 314)	0	0
Hypernatremia: Grade 1 (n =338, 319)	34	23
Hypernatremia: Grade 2 (n =338, 319)	19	14
Hypernatremia: Grade 3 (n =338, 319)	3	1
Hypernatremia: Grade 4 (n =338, 319)	0	2
Hypoalbuminemia: Grade 1 (n =337, 319)	37	25
Hypoalbuminemia: Grade 2 (n =337, 319)	11	31
Hypoalbuminemia: Grade 3 (n =337, 319)	1	2
Hypoalbuminemia: Grade 4 (n =337, 319)	0	0
Hypocalcemia: Grade 1 (n =336, 319)	25	67
Hypocalcemia: Grade 2 (n =336, 319)	4	18
Hypocalcemia: Grade 3 (n =336, 319)	2	2
Hypocalcemia: Grade 4 (n =336, 319)	1	2
Hypoglycemia: Grade 1 (n =336, 319)	23	9
Hypoglycemia: Grade 2 (n =336, 319)	12	16
Hypoglycemia: Grade 3 (n =336, 319)	1	1
Hypoglycemia: Grade 4 (n =336, 319)	0	0
Hypokalemia: Grade 1 (n =333, 314)	22	21
Hypokalemia: Grade 2 (n =333, 314)	0	0
Hypokalemia: Grade 3 (n =333, 314)	0	5
Hypokalemia: Grade 4 (n =333, 314)	0	0
Hyponatremia: Grade 1 (n =338, 319)	33	27
Hyponatremia: Grade 2 (n =338, 319)	0	0
Hyponatremia: Grade 3 (n =338, 319)	11	6
Hyponatremia: Grade 4 (n =338, 319)	1	1
Hypophosphatemia: Grade 1 (n =336, 318)	4	8
Hypophosphatemia: Grade 2 (n =336, 318)	33	99
Hypophosphatemia: Grade 3 (n =336, 318)	6	51
Hypophosphatemia: Grade 4 (n =336, 318)	0	0
Lipase: Grade 1 (n =338, 319)	53	76
Lipase: Grade 2 (n =338, 319)	22	25
Lipase: Grade 3 (n =338, 319)	14	40
Lipase: Grade 4 (n =338, 319)	2	7

10. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities: Urinalysis
Description	Urinalysis included urine blood/ hemoglobin, glucose and protein. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.
Time Frame	From initiation of treatment up to follow-up period (up to 3 years)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication with treatment assignments designated according to actual study treatment received. Here, "n" signifies number of participants available for specified categories for each arm respectively.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	359	355
Measure Type: Number; Unit of Measure: Participants
Urine blood/ hemoglobin: Grade 1 (n =304, 272)	45	35
Urine blood/ hemoglobin: Grade 2 (n =304, 272)	1	0
Urine blood/ hemoglobin: Grade 3 (n =304, 272)	0	0
Urine blood/ hemoglobin: Grade 4 (n =304, 272)	0	0
Urine glucose: Grade 1 (n =322, 286)	12	13
Urine glucose: Grade 2 (n =322, 286)	0	3
Urine glucose: Grade 3 (n =322, 286)	0	0
Urine glucose: Grade 4 (n =322, 286)	1	1
Urine protein: Grade 1 (n =326, 289)	105	91
Urine protein: Grade 2 (n =326, 289)	31	27
Urine protein: Grade 3 (n =326, 289)	27	21
Urine protein: Grade 4 (n =326, 289)	9	7

11. Secondary Outcome

Title	Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15) Score
Description	FKSI was used to assess quality of life (QoL) for those diagnosed with renal cell cancer and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert-type scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher scores indicate greater presence of symptoms.
Time Frame	Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized. Here, "n" signifies those participants who were evaluable for the specified time points.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	361	362
Mean (Standard Deviation); Unit of Measure: Units on a scale
Baseline (n =346, 342)	43.199 (8.416)	43.339 (8.162)
Cycle 2/Day1 (n =319, 296)	42.351 (8.305)	41.668 (7.696)
Cycle 3/Day1 (n =279, 246)	42.590 (7.729)	42.424 (7.888)
Cycle 4/Day1 (n =257, 221)	42.791 (8.180)	43.424 (7.345)
Cycle 5/Day1 (n =238, 203)	42.968 (8.152)	42.907 (7.255)
Cycle 6/Day1 (n =213, 179)	42.949 (7.842)	43.057 (7.724)
Cycle 7/Day1 (n =206, 158)	42.747 (7.621)	43.578 (7.621)
Cycle 8/Day1 (n =177, 136)	43.580 (7.578)	44.074 (7.757)
Cycle 9/Day1 (n =163, 118)	43.191 (8.300)	44.518 (6.511)
Cycle 10/Day1 (n =146, 96)	43.312 (8.564)	44.771 (7.155)
Cycle 11/Day1 (n =122, 85)	44.119 (8.306)	44.438 (7.388)
Cycle 12/Day1 (n =110, 70)	44.517 (8.212)	44.357 (7.247)
Cycle 13/Day1 (n =92, 58)	44.492 (7.972)	45.261 (7.840)
Cycle 14/Day1 (n =81, 54)	44.485 (8.204)	44.898 (7.495)
Cycle 15/Day1 (n =61, 38)	45.291 (7.095)	45.053 (6.682)
Cycle 16/Day1 (n =52, 34)	45.217 (7.656)	44.445 (7.160)
Cycle 17/Day1 (n =47, 28)	45.242 (7.344)	44.438 (7.683)
Cycle 18/Day1 (n =36, 22)	44.861 (7.769)	44.182 (7.228)
Cycle 19/Day1 (n =29, 14)	45.379 (6.662)	45.026 (7.705)
Cycle 20/Day1 (n =20, 12)	47.050 (5.375)	44.780 (6.689)
Cycle 21/Day1 (n =15, 7)	45.850 (5.209)	44.494 (6.153)
End of treatment (n=163, 191)	38.328 (9.472)	38.457 (8.787)
Follow up (n =80, 110)	41.919 (8.318)	40.028 (9.048)

12. Secondary Outcome

Title	Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Score
Description	FKSI-DRS was used to assess quality of life for those diagnosed with renal cell cancer and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert-type scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptoms) to 36 (very much); higher scores indicate greater presence of symptoms.
Time Frame	Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized. Here, "n" signifies those participants who were evaluable for the specified time points.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	361	362
Mean (Standard Deviation); Unit of Measure: Units on a scale
Baseline (n =346, 341)	28.874 (5.187)	28.975 (5.193)
Cycle 2/Day1 (n =319, 295)	28.211 (4.920)	28.399 (5.064)
Cycle 3/Day1 (n =279, 244)	28.640 (4.837)	28.640 (4.868)
Cycle 4/Day1 (n =257, 220)	28.822 (4.952)	29.130 (4.322)
Cycle 5/Day1 (n =238, 202)	28.869 (4.880)	29.007 (4.379)
Cycle 6/Day1 (n =213, 178)	29.159 (4.462)	29.098 (4.697)
Cycle 7/Day1 (n =206, 157)	29.042 (4.581)	29.361 (4.558)
Cycle 8/Day1 (n =177, 135)	29.520 (4.346)	29.619 (4.386)
Cycle 9/Day1 (n =163, 117)	29.194 (4.937)	29.884 (3.838)
Cycle 10/Day1 (n =146, 96)	29.343 (4.907)	29.604 (3.959)
Cycle 11/Day1 (n =122, 85)	29.762 (4.943)	29.366 (4.404)
Cycle 12/Day1 (n =110, 70)	29.764 (4.507)	29.257 (4.299)
Cycle 13/Day1 (n =92, 58)	29.594 (4.205)	29.666 (4.710)
Cycle 14/Day1 (n =81, 54)	29.711 (4.313)	29.820 (4.333)
Cycle 15/Day1 (n =61, 38)	30.324 (3.582)	29.500 (3.454)
Cycle 16/Day1 (n =52, 34)	30.430 (3.443)	29.474 (4.146)
Cycle 17/Day1 (n =47, 28)	30.551 (3.331)	28.737 (4.930)
Cycle 18/Day1 (n =36, 22)	30.194 (3.992)	29.045 (4.520)
Cycle 19/Day1 (n =29, 14)	30.130 (3.636)	29.286 (4.795)
Cycle 20/Day1 (n =20, 12)	31.300 (2.736)	29.250 (4.025)
Cycle 21/Day1 (n =15, 7)	31.067 (3.173)	30.143 (4.100)
End of Treatment (n =163, 191)	26.288 (5.806)	26.517 (5.614)
Follow up (n =80, 110)	28.263 (4.802)	27.516 (5.577)

13. Secondary Outcome

Title	Euro Quality of Life Questionnaire- 5 Dimension (EQ-5D): Health State Profile Utility Score
Description	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility or index score. Health state profile component assesses level of health for 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain was rated on a 3-point response scale (1= no problems, 2= some/moderate problems and 3= extreme problems). Scoring formula developed by EuroQol Group assigned a utility value for each domain in the profile. Score were transformed and resulted in a total score range of 0 to 1, with higher scores indicating better health.
Time Frame	Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized. Here, "n" signifies those participants who were evaluable for the specified time points.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	361	362
Mean (Standard Deviation); Unit of Measure: Units on a scale
Baseline (n =347, 341)	0.732 (0.275)	0.731 (0.257)
Cycle 2/Day1 (n =326, 307)	0.716 (0.267)	0.696 (0.237)
Cycle 3/Day1 (n =287, 248)	0.722 (0.243)	0.709 (0.239)
Cycle 4/Day1 (n =262, 226)	0.730 (0.236)	0.716 (0.248)
Cycle 5/Day1 (n =244, 207)	0.730 (0.237)	0.711 (0.243)
Cycle 6/Day1 (n =221, 178)	0.734 (0.230)	0.704 (0.246)
Cycle 7/Day1 (n =213, 163)	0.718 (0.267)	0.728 (0.228)
Cycle 8/Day1 (n =181, 136)	0.756 (0.236)	0.702 (0.259)
Cycle 9/Day1 (n =169, 120)	0.760 (0.227)	0.730 (0.229)
Cycle 10/Day1 (n =151, 98)	0.734 (0.243)	0.730 (0.233)
Cycle 11/Day1 (n =126, 87)	0.764 (0.235)	0.724 (0.250)
Cycle 12/Day1 (n =110, 73)	0.744 (0.244)	0.734 (0.232)
Cycle 13/Day1 (n =96, 61)	0.760 (0.211)	0.753 (0.232)
Cycle 14/Day1 (n =80, 57)	0.723 (0.239)	0.752 (0.211)
Cycle 15/Day1 (n =63, 41)	0.730 (0.255)	0.758 (0.191)
Cycle 16/Day1 (n =54, 37)	0.749 (0.220)	0.785 (0.158)
Cycle 17/Day1 (n =48, 29)	0.779 (0.186)	0.764 (0.193)
Cycle 18/Day1 (n =37, 20)	0.755 (0.204)	0.755 (0.208)
Cycle 19/Day1 (n =29, 14)	0.734 (0.253)	0.804 (0.184)
Cycle 20/Day1 (n =21, 12)	0.794 (0.220)	0.771 (0.182)
Cycle 21/Day1 (n =16, 7)	0.700 (0.273)	0.771 (0.182)
End of Treatment (n =169, 196)	0.608 (0.316)	0.612 (0.310)
Follow up (n =76, 106)	0.682 (0.294)	0.666 (0.295)

14. Secondary Outcome

Title	Euro Quality of Life Questionnaire- 5 Dimension (EQ-5D): Visual Analog Scale (VAS)
Description	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. VAS component: participants rated their current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health.
Time Frame	Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized. Here, "n" signifies those participants who were evaluable for the specified time points.

Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description:	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
Overall Number of Participants Analyzed	361	362
Mean (Standard Deviation); Unit of Measure: Units on a scale
Baseline (n =341, 339)	70.560 (19.187)	70.351 (17.403)
Cycle 2/Day1 (n =317, 302)	69.003 (20.195)	67.606 (18.265)
Cycle 3/Day1 (n =280, 250)	69.843 (17.927)	69.712 (18.429)
Cycle 4/Day1 (n =261, 224)	69.180 (18.636)	70.759 (17.189)
Cycle 5/Day1 (n =244, 205)	69.705 (18.330)	71.888 (16.999)
Cycle 6/Day1 (n =220, 178)	69.900 (18.168)	71.365 (17.019)
Cycle 7/Day1 (n =209, 163)	69.919 (18.063)	72.282 (17.521)
Cycle 8/Day1 (n =180, 139)	70.756 (19.183)	71.475 (18.523)
Cycle 9/Day1 (n =168, 121)	70.667 (18.556)	73.380 (17.473)
Cycle 10/Day1 (n =151, 98)	70.629 (18.680)	75.102 (14.854)
Cycle 11/Day1 (n =126, 87)	72.103 (18.064)	74.586 (15.161)
Cycle 12/Day1 (n =111, 73)	71.730 (17.276)	73.959 (15.852)
Cycle 13/Day1 (n =94, 61)	70.723 (19.147)	75.693 (14.571)
Cycle 14/Day1 (n =81, 58)	69.420 (20.286)	75.362 (15.875)
Cycle 15/Day1 (n =62, 42)	73.016 (15.325)	75.357 (15.368)
Cycle 16/Day1 (n =52, 37)	70.269 (19.272)	73.676 (15.699)
Cycle 17/Day1 (n =48, 30)	71.375 (17.840)	73.767 (16.298)
Cycle 18/Day1 (n =37, 23)	70.459 (18.853)	73.870 (16.904)
Cycle 19/Day1 (n =29, 14)	71.034 (16.963)	70.571 (17.956)
Cycle 20/Day1 (n =21, 12)	73.143 (15.347)	66.917 (17.758)
Cycle 21/Day1 (n =16, 7)	74.563 (16.054)	64.714 (16.183)
End of Treatment (n =166, 197)	61.759 (21.668)	61.690 (20.973)
Follow up (n =76, 109)	64.382 (21.392)	66.037 (19.754)

Adverse Events

Time Frame	From initiation of treatment up to follow-up period (up to 3 years)
Adverse Event Reporting Description	Same event may appear as both AE and SAE, what is presented are distinct event. Event may be classified as serious in 1 participant, nonserious in other, or 1 participant may have experienced both serious, nonserious event during study.
Arm/Group Title	Axitinib 5 mg	Sorafenib 400 mg
Arm/Group Description	Axitinib (AG-013736) 5 milligram (mg) tablet administered orally twice daily in cycles of 4 weeks.	Sorafenib 400 mg tablet administered orally twice daily in cycles of 4 weeks.
All-Cause Mortality
	Axitinib 5 mg	Sorafenib 400 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Axitinib 5 mg	Sorafenib 400 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	146/359 (40.67%)	127/355 (35.77%)
Blood and lymphatic system disorders
Anaemia * 1	0/359 (0.00%)	8/355 (2.25%)
Splenic infarction * 1	0/359 (0.00%)	1/355 (0.28%)
Cardiac disorders
Acute coronary syndrome * 1	0/359 (0.00%)	2/355 (0.56%)
Acute myocardial infarction * 1	2/359 (0.56%)	0/355 (0.00%)
Angina pectoris * 1	0/359 (0.00%)	2/355 (0.56%)
Arrhythmia supraventricular * 1	1/359 (0.28%)	0/355 (0.00%)
Arteriosclerosis coronary artery * 1	1/359 (0.28%)	0/355 (0.00%)
Atrial fibrillation * 1	2/359 (0.56%)	0/355 (0.00%)
Atrial flutter * 1	1/359 (0.28%)	0/355 (0.00%)
Atrioventricular block * 1	0/359 (0.00%)	1/355 (0.28%)
Bradycardia * 1	1/359 (0.28%)	0/355 (0.00%)
Cardiac arrest * 1	1/359 (0.28%)	0/355 (0.00%)
Cardiac failure * 1	2/359 (0.56%)	1/355 (0.28%)
Cardiopulmonary failure * 1	2/359 (0.56%)	1/355 (0.28%)
Congestive cardiomyopathy * 1	0/359 (0.00%)	1/355 (0.28%)
Coronary artery insufficiency * 1	1/359 (0.28%)	0/355 (0.00%)
Haemorrhage coronary artery * 1	1/359 (0.28%)	0/355 (0.00%)
Mitral valve incompetence * 1	1/359 (0.28%)	0/355 (0.00%)
Myocardial infarction * 1	6/359 (1.67%)	4/355 (1.13%)
Myocardial ischaemia * 1	1/359 (0.28%)	0/355 (0.00%)
Prinzmetal angina * 1	1/359 (0.28%)	0/355 (0.00%)
Supraventricular tachycardia * 1	1/359 (0.28%)	0/355 (0.00%)
Tachycardia * 1	0/359 (0.00%)	1/355 (0.28%)
Endocrine disorders
Adrenal insufficiency * 1	0/359 (0.00%)	1/355 (0.28%)
Hypothyroidism * 1	1/359 (0.28%)	0/355 (0.00%)
Secondary hypothyroidism * 1	1/359 (0.28%)	0/355 (0.00%)
Thyroiditis * 1	0/359 (0.00%)	1/355 (0.28%)
Eye disorders
Diplopia * 1	1/359 (0.28%)	0/355 (0.00%)
Retinal artery embolism * 1	0/359 (0.00%)	1/355 (0.28%)
Retinal artery occlusion * 1	1/359 (0.28%)	0/355 (0.00%)
Retinal vein occlusion * 1	1/359 (0.28%)	0/355 (0.00%)
Retinal vein thrombosis * 1	1/359 (0.28%)	0/355 (0.00%)
Gastrointestinal disorders
Abdominal pain * 1	1/359 (0.28%)	2/355 (0.56%)
Anal fistula * 1	1/359 (0.28%)	0/355 (0.00%)
Ascites * 1	0/359 (0.00%)	1/355 (0.28%)
Colitis ulcerative * 1	0/359 (0.00%)	1/355 (0.28%)
Constipation * 1	2/359 (0.56%)	1/355 (0.28%)
Diarrhoea * 1	8/359 (2.23%)	5/355 (1.41%)
Duodenal ulcer haemorrhage * 1	0/359 (0.00%)	1/355 (0.28%)
Enterocolitis * 1	0/359 (0.00%)	1/355 (0.28%)
Gastric haemorrhage * 1	2/359 (0.56%)	0/355 (0.00%)
Gastric ulcer * 1	1/359 (0.28%)	0/355 (0.00%)
Gastritis * 1	0/359 (0.00%)	1/355 (0.28%)
Gastrointestinal haemorrhage * 1	0/359 (0.00%)	5/355 (1.41%)
Gastrointestinal perforation * 1	1/359 (0.28%)	0/355 (0.00%)
Haematemesis * 1	0/359 (0.00%)	1/355 (0.28%)
Inguinal hernia * 1	3/359 (0.84%)	0/355 (0.00%)
Intestinal obstruction * 1	4/359 (1.11%)	1/355 (0.28%)
Lower gastrointestinal haemorrhage * 1	1/359 (0.28%)	1/355 (0.28%)
Melaena * 1	1/359 (0.28%)	0/355 (0.00%)
Nausea * 1	1/359 (0.28%)	1/355 (0.28%)
Pancreatitis * 1	0/359 (0.00%)	1/355 (0.28%)
Rectal haemorrhage * 1	0/359 (0.00%)	1/355 (0.28%)
Retroperitoneal haemorrhage * 1	0/359 (0.00%)	1/355 (0.28%)
Small intestinal obstruction * 1	1/359 (0.28%)	0/355 (0.00%)
Subileus * 1	0/359 (0.00%)	1/355 (0.28%)
Upper gastrointestinal haemorrhage * 1	0/359 (0.00%)	1/355 (0.28%)
Vomiting * 1	5/359 (1.39%)	2/355 (0.56%)
General disorders
Asthenia * 1	2/359 (0.56%)	1/355 (0.28%)
Chest pain * 1	2/359 (0.56%)	2/355 (0.56%)
Chills * 1	1/359 (0.28%)	0/355 (0.00%)
Death * 1	3/359 (0.84%)	6/355 (1.69%)
Device dislocation * 1	0/359 (0.00%)	1/355 (0.28%)
Disease progression * 1	32/359 (8.91%)	18/355 (5.07%)
Fatigue * 1	4/359 (1.11%)	0/355 (0.00%)
General physical health deterioration * 1	3/359 (0.84%)	5/355 (1.41%)
Hernia * 1	1/359 (0.28%)	0/355 (0.00%)
Impaired healing * 1	0/359 (0.00%)	1/355 (0.28%)
Inflammation * 1	0/359 (0.00%)	1/355 (0.28%)
Malaise * 1	1/359 (0.28%)	0/355 (0.00%)
Mucosal inflammation * 1	1/359 (0.28%)	0/355 (0.00%)
Oedema * 1	1/359 (0.28%)	0/355 (0.00%)
Pain * 1	2/359 (0.56%)	3/355 (0.85%)
Pyrexia * 1	7/359 (1.95%)	5/355 (1.41%)
Hepatobiliary disorders
Biliary dilatation * 1	0/359 (0.00%)	1/355 (0.28%)
Budd-Chiari syndrome * 1	1/359 (0.28%)	0/355 (0.00%)
Cholangitis * 1	1/359 (0.28%)	1/355 (0.28%)
Cholecystitis * 1	1/359 (0.28%)	1/355 (0.28%)
Cholelithiasis * 1	0/359 (0.00%)	1/355 (0.28%)
Hepatic function abnormal * 1	0/359 (0.00%)	1/355 (0.28%)
Immune system disorders
Hypersensitivity * 1	1/359 (0.28%)	0/355 (0.00%)
Infections and infestations
Abdominal abscess * 1	1/359 (0.28%)	0/355 (0.00%)
Appendicitis * 1	1/359 (0.28%)	2/355 (0.56%)
Aspergillus infection * 1	0/359 (0.00%)	1/355 (0.28%)
Bacterial diarrhoea * 1	1/359 (0.28%)	0/355 (0.00%)
Cellulitis * 1	0/359 (0.00%)	1/355 (0.28%)
Diverticulitis * 1	0/359 (0.00%)	1/355 (0.28%)
Erysipelas * 1	1/359 (0.28%)	0/355 (0.00%)
Gastroenteritis * 1	1/359 (0.28%)	0/355 (0.00%)
Gastroenteritis viral * 1	1/359 (0.28%)	0/355 (0.00%)
Herpes zoster * 1	0/359 (0.00%)	1/355 (0.28%)
Infection * 1	3/359 (0.84%)	0/355 (0.00%)
Intervertebral discitis * 1	0/359 (0.00%)	1/355 (0.28%)
Lower respiratory tract infection * 1	0/359 (0.00%)	4/355 (1.13%)
Lower respiratory tract infection bacterial * 1	1/359 (0.28%)	0/355 (0.00%)
Lung infection * 1	0/359 (0.00%)	1/355 (0.28%)
Muscle abscess * 1	0/359 (0.00%)	1/355 (0.28%)
Pneumonia * 1	5/359 (1.39%)	4/355 (1.13%)
Pneumonia streptococcal * 1	1/359 (0.28%)	0/355 (0.00%)
Pneumonia viral * 1	1/359 (0.28%)	0/355 (0.00%)
Pulmonary tuberculosis * 1	0/359 (0.00%)	1/355 (0.28%)
Pyelonephritis * 1	0/359 (0.00%)	1/355 (0.28%)
Respiratory tract infection * 1	1/359 (0.28%)	1/355 (0.28%)
Sepsis * 1	1/359 (0.28%)	2/355 (0.56%)
Septic shock * 1	0/359 (0.00%)	1/355 (0.28%)
Urinary tract infection * 1	2/359 (0.56%)	2/355 (0.56%)
Injury, poisoning and procedural complications
Fall * 1	1/359 (0.28%)	2/355 (0.56%)
Femoral neck fracture * 1	1/359 (0.28%)	0/355 (0.00%)
Gastrointestinal anastomotic leak * 1	1/359 (0.28%)	0/355 (0.00%)
Humerus fracture * 1	1/359 (0.28%)	0/355 (0.00%)
Laceration * 1	1/359 (0.28%)	0/355 (0.00%)
Lumbar vertebral fracture * 1	2/359 (0.56%)	0/355 (0.00%)
Procedural pain * 1	1/359 (0.28%)	0/355 (0.00%)
Radiation pneumonitis * 1	1/359 (0.28%)	0/355 (0.00%)
Rib fracture * 1	0/359 (0.00%)	1/355 (0.28%)
Soft tissue injury * 1	0/359 (0.00%)	1/355 (0.28%)
Spinal compression fracture * 1	1/359 (0.28%)	0/355 (0.00%)
Investigations
Neutrophil count abnormal * 1	1/359 (0.28%)	0/355 (0.00%)
Alanine aminotransferase increased * 1	0/359 (0.00%)	1/355 (0.28%)
Aspartate aminotransferase increased * 1	0/359 (0.00%)	1/355 (0.28%)
Blood alkaline phosphatase increased * 1	0/359 (0.00%)	1/355 (0.28%)
Blood creatinine increased * 1	2/359 (0.56%)	1/355 (0.28%)
Blood lactate dehydrogenase increased * 1	0/359 (0.00%)	1/355 (0.28%)
C-reactive protein increased * 1	0/359 (0.00%)	1/355 (0.28%)
Gamma-glutamyltransferase increased * 1	0/359 (0.00%)	1/355 (0.28%)
Hepatic enzyme increased * 1	0/359 (0.00%)	1/355 (0.28%)
Metabolism and nutrition disorders
Decreased appetite * 1	3/359 (0.84%)	0/355 (0.00%)
Dehydration * 1	10/359 (2.79%)	1/355 (0.28%)
Hypercalcaemia * 1	1/359 (0.28%)	2/355 (0.56%)
Hyperkalaemia * 1	2/359 (0.56%)	1/355 (0.28%)
Hypocalcaemia * 1	0/359 (0.00%)	1/355 (0.28%)
Hypoglycaemia * 1	1/359 (0.28%)	0/355 (0.00%)
Hypokalaemia * 1	2/359 (0.56%)	0/355 (0.00%)
Hyponatraemia * 1	1/359 (0.28%)	3/355 (0.85%)
Hypovolaemia * 1	1/359 (0.28%)	0/355 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	1/359 (0.28%)	1/355 (0.28%)
Back pain * 1	3/359 (0.84%)	2/355 (0.56%)
Flank pain * 1	0/359 (0.00%)	1/355 (0.28%)
Musculoskeletal chest pain * 1	0/359 (0.00%)	1/355 (0.28%)
Pain in extremity * 1	2/359 (0.56%)	0/355 (0.00%)
Polyarthritis * 1	0/359 (0.00%)	1/355 (0.28%)
Spinal column stenosis * 1	0/359 (0.00%)	1/355 (0.28%)
Spondylolisthesis * 1	0/359 (0.00%)	1/355 (0.28%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis * 1	1/359 (0.28%)	0/355 (0.00%)
Metastatic pain * 1	0/359 (0.00%)	1/355 (0.28%)
Neoplasm progression * 1	1/359 (0.28%)	0/355 (0.00%)
Renal cell carcinoma * 1	1/359 (0.28%)	1/355 (0.28%)
Squamous cell carcinoma * 1	0/359 (0.00%)	1/355 (0.28%)
Tumour associated fever * 1	1/359 (0.28%)	0/355 (0.00%)
Nervous system disorders
Aphasia * 1	1/359 (0.28%)	0/355 (0.00%)
Balance disorder * 1	0/359 (0.00%)	1/355 (0.28%)
Central nervous system haemorrhage * 1	1/359 (0.28%)	0/355 (0.00%)
Cerebral infarction * 1	0/359 (0.00%)	1/355 (0.28%)
Cerebral ischaemia * 1	0/359 (0.00%)	1/355 (0.28%)
Cerebrovascular accident * 1	2/359 (0.56%)	1/355 (0.28%)
Dizziness * 1	3/359 (0.84%)	0/355 (0.00%)
Headache * 1	1/359 (0.28%)	0/355 (0.00%)
Hemiparesis * 1	0/359 (0.00%)	1/355 (0.28%)
Ischaemic stroke * 1	0/359 (0.00%)	1/355 (0.28%)
Leukoencephalopathy * 1	1/359 (0.28%)	0/355 (0.00%)
Loss of consciousness * 1	2/359 (0.56%)	0/355 (0.00%)
Meningeal disorder * 1	1/359 (0.28%)	0/355 (0.00%)
Monoplegia * 1	0/359 (0.00%)	1/355 (0.28%)
Presyncope * 1	1/359 (0.28%)	0/355 (0.00%)
Seizure * 1	1/359 (0.28%)	0/355 (0.00%)
Spinal cord compression * 1	2/359 (0.56%)	0/355 (0.00%)
Syncope * 1	2/359 (0.56%)	0/355 (0.00%)
Transient ischaemic attack * 1	3/359 (0.84%)	0/355 (0.00%)
Psychiatric disorders
Anxiety * 1	0/359 (0.00%)	1/355 (0.28%)
Confusional state * 1	1/359 (0.28%)	0/355 (0.00%)
Disorientation * 1	1/359 (0.28%)	0/355 (0.00%)
Mental status changes * 1	1/359 (0.28%)	1/355 (0.28%)
Renal and urinary disorders
Acute kidney injury * 1	4/359 (1.11%)	2/355 (0.56%)
Acute prerenal failure * 1	1/359 (0.28%)	0/355 (0.00%)
Haematuria * 1	1/359 (0.28%)	0/355 (0.00%)
Nephropathy * 1	0/359 (0.00%)	1/355 (0.28%)
Oliguria * 1	0/359 (0.00%)	1/355 (0.28%)
Renal failure * 1	1/359 (0.28%)	0/355 (0.00%)
Urinary retention * 1	1/359 (0.28%)	0/355 (0.00%)
Reproductive system and breast disorders
Benign prostatic hyperplasia * 1 [1]	1/265 (0.38%)	0/258 (0.00%)
Menometrorrhagia * 1 [1]	0/96 (0.00%)	1/104 (0.96%)
Vaginal polyp * 1 [1]	1/96 (1.04%)	0/104 (0.00%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease * 1	0/359 (0.00%)	1/355 (0.28%)
Cough * 1	0/359 (0.00%)	1/355 (0.28%)
Dyspnoea * 1	7/359 (1.95%)	3/355 (0.85%)
Dyspnoea exertional * 1	1/359 (0.28%)	0/355 (0.00%)
Epistaxis * 1	1/359 (0.28%)	1/355 (0.28%)
Haemoptysis * 1	1/359 (0.28%)	2/355 (0.56%)
Haemothorax * 1	0/359 (0.00%)	1/355 (0.28%)
Interstitial lung disease * 1	1/359 (0.28%)	0/355 (0.00%)
Lung disorder * 1	1/359 (0.28%)	0/355 (0.00%)
Pleural effusion * 1	3/359 (0.84%)	5/355 (1.41%)
Pleurisy * 1	0/359 (0.00%)	1/355 (0.28%)
Pneumothorax * 1	4/359 (1.11%)	1/355 (0.28%)
Pneumothorax spontaneous * 1	1/359 (0.28%)	0/355 (0.00%)
Pulmonary embolism * 1	7/359 (1.95%)	1/355 (0.28%)
Pulmonary haemorrhage * 1	0/359 (0.00%)	2/355 (0.56%)
Respiratory distress * 1	1/359 (0.28%)	0/355 (0.00%)
Skin and subcutaneous tissue disorders
Erythema multiforme * 1	0/359 (0.00%)	3/355 (0.85%)
Hyperhidrosis * 1	1/359 (0.28%)	0/355 (0.00%)
Palmar-plantar erythrodysaesthesia syndrome * 1	0/359 (0.00%)	1/355 (0.28%)
Pustular psoriasis * 1	0/359 (0.00%)	1/355 (0.28%)
Rash * 1	0/359 (0.00%)	2/355 (0.56%)
Urticaria * 1	1/359 (0.28%)	0/355 (0.00%)
Surgical and medical procedures
Pain management * 1	0/359 (0.00%)	1/355 (0.28%)
Vertebroplasty * 1	0/359 (0.00%)	1/355 (0.28%)
Vascular disorders
Accelerated hypertension * 1	1/359 (0.28%)	0/355 (0.00%)
Deep vein thrombosis * 1	1/359 (0.28%)	1/355 (0.28%)
Hypertension * 1	1/359 (0.28%)	2/355 (0.56%)
Hypertensive crisis * 1	1/359 (0.28%)	0/355 (0.00%)
Hypotension * 1	1/359 (0.28%)	4/355 (1.13%)
Infarction * 1	0/359 (0.00%)	1/355 (0.28%)
Jugular vein thrombosis * 1	1/359 (0.28%)	0/355 (0.00%)
Subclavian vein thrombosis * 1	1/359 (0.28%)	0/355 (0.00%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 18.1; [1] This event was gender specific.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Axitinib 5 mg	Sorafenib 400 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	337/359 (93.87%)	346/355 (97.46%)
Blood and lymphatic system disorders
Anaemia * 1	18/359 (5.01%)	44/355 (12.39%)
Endocrine disorders
Hypothyroidism * 1	74/359 (20.61%)	33/355 (9.30%)
Gastrointestinal disorders
Abdominal pain * 1	55/359 (15.32%)	46/355 (12.96%)
Abdominal pain upper * 1	37/359 (10.31%)	16/355 (4.51%)
Constipation * 1	79/359 (22.01%)	82/355 (23.10%)
Diarrhoea * 1	208/359 (57.94%)	195/355 (54.93%)
Dyspepsia * 1	39/359 (10.86%)	15/355 (4.23%)
Flatulence * 1	20/359 (5.57%)	8/355 (2.25%)
Nausea * 1	128/359 (35.65%)	84/355 (23.66%)
Stomatitis * 1	60/359 (16.71%)	47/355 (13.24%)
Vomiting * 1	95/359 (26.46%)	69/355 (19.44%)
General disorders
Asthenia * 1	78/359 (21.73%)	57/355 (16.06%)
Chest pain * 1	23/359 (6.41%)	20/355 (5.63%)
Fatigue * 1	151/359 (42.06%)	122/355 (34.37%)
Mucosal inflammation * 1	61/359 (16.99%)	45/355 (12.68%)
Oedema peripheral * 1	22/359 (6.13%)	22/355 (6.20%)
Pain * 1	19/359 (5.29%)	17/355 (4.79%)
Pyrexia * 1	26/359 (7.24%)	40/355 (11.27%)
Infections and infestations
Nasopharyngitis * 1	25/359 (6.96%)	13/355 (3.66%)
Investigations
Blood thyroid stimulating hormone increased * 1	19/359 (5.29%)	11/355 (3.10%)
Lipase increased * 1	13/359 (3.62%)	22/355 (6.20%)
Weight decreased * 1	111/359 (30.92%)	83/355 (23.38%)
Metabolism and nutrition disorders
Decreased appetite * 1	140/359 (39.00%)	112/355 (31.55%)
Dehydration * 1	18/359 (5.01%)	10/355 (2.82%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	62/359 (17.27%)	46/355 (12.96%)
Back pain * 1	59/359 (16.43%)	54/355 (15.21%)
Muscle spasms * 1	11/359 (3.06%)	21/355 (5.92%)
Musculoskeletal pain * 1	28/359 (7.80%)	27/355 (7.61%)
Myalgia * 1	28/359 (7.80%)	12/355 (3.38%)
Pain in extremity * 1	49/359 (13.65%)	53/355 (14.93%)
Nervous system disorders
Dizziness * 1	33/359 (9.19%)	21/355 (5.92%)
Dysgeusia * 1	43/359 (11.98%)	31/355 (8.73%)
Headache * 1	55/359 (15.32%)	43/355 (12.11%)
Psychiatric disorders
Insomnia * 1	33/359 (9.19%)	21/355 (5.92%)
Renal and urinary disorders
Proteinuria * 1	49/359 (13.65%)	32/355 (9.01%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	68/359 (18.94%)	70/355 (19.72%)
Dysphonia * 1	116/359 (32.31%)	49/355 (13.80%)
Dyspnoea * 1	64/359 (17.83%)	53/355 (14.93%)
Dyspnoea exertional * 1	18/359 (5.01%)	11/355 (3.10%)
Epistaxis * 1	28/359 (7.80%)	19/355 (5.35%)
Haemoptysis * 1	8/359 (2.23%)	18/355 (5.07%)
Oropharyngeal pain * 1	22/359 (6.13%)	21/355 (5.92%)
Skin and subcutaneous tissue disorders
Alopecia * 1	18/359 (5.01%)	122/355 (34.37%)
Dry skin * 1	36/359 (10.03%)	42/355 (11.83%)
Erythema * 1	12/359 (3.34%)	39/355 (10.99%)
Palmar-plantar erythrodysaesthesia syndrome * 1	100/359 (27.86%)	183/355 (51.55%)
Pruritus * 1	25/359 (6.96%)	48/355 (13.52%)
Rash * 1	53/359 (14.76%)	109/355 (30.70%)
Vascular disorders
Hypertension * 1	156/359 (43.45%)	107/355 (30.14%)
Hypotension * 1	19/359 (5.29%)	6/355 (1.69%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 18.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Murphy DA, Rini BI, Escudier B, Motzer RJ, Wang P, Li S, Williams JA, Tarazi JC, Martini JF. Angiogenic and immunomodulatory biomarkers in axitinib-treated patients with advanced renal cell carcinoma. Future Oncol. 2020 Jun;16(17):1199-1210. doi: 10.2217/fon-2020-0212. Epub 2020 May 4.

Bracarda S, Bamias A, Casper J, Negrier S, Sella A, Staehler M, Tarazi J, Felici A, Rosbrook B, Jardinaud-Lopez M, Escudier B. Is Axitinib Still a Valid Option for mRCC in the Second-Line Setting? Prognostic Factor Analyses From the AXIS Trial. Clin Genitourin Cancer. 2019 Jun;17(3):e689-e703. doi: 10.1016/j.clgc.2019.03.017. Epub 2019 Apr 1.

de Velasco G, McKay RR, Lin X, Moreira RB, Simantov R, Choueiri TK. Comprehensive Analysis of Survival Outcomes in Non-Clear Cell Renal Cell Carcinoma Patients Treated in Clinical Trials. Clin Genitourin Cancer. 2017 Dec;15(6):652-660.e1. doi: 10.1016/j.clgc.2017.03.004. Epub 2017 Mar 21.

Grunwald V, Lin X, Kalanovic D, Simantov R. Early Tumour Shrinkage: A Tool for the Detection of Early Clinical Activity in Metastatic Renal Cell Carcinoma. Eur Urol. 2016 Dec;70(6):1006-1015. doi: 10.1016/j.eururo.2016.05.010. Epub 2016 May 26.

Grunwald V, McKay RR, Krajewski KM, Kalanovic D, Lin X, Perkins JJ, Simantov R, Choueiri TK. Depth of remission is a prognostic factor for survival in patients with metastatic renal cell carcinoma. Eur Urol. 2015 May;67(5):952-8. doi: 10.1016/j.eururo.2014.12.036. Epub 2015 Jan 7.

Escudier B, Michaelson MD, Motzer RJ, Hutson TE, Clark JI, Lim HY, Porfiri E, Zalewski P, Kannourakis G, Staehler M, Tarazi J, Rosbrook B, Cisar L, Hariharan S, Kim S, Rini BI. Axitinib versus sorafenib in advanced renal cell carcinoma: subanalyses by prior therapy from a randomised phase III trial. Br J Cancer. 2014 Jun 10;110(12):2821-8. doi: 10.1038/bjc.2014.244. Epub 2014 May 13.

Ueda T, Uemura H, Tomita Y, Tsukamoto T, Kanayama H, Shinohara N, Tarazi J, Chen C, Kim S, Ozono S, Naito S, Akaza H. Efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from the global randomized Phase 3 AXIS trial. Jpn J Clin Oncol. 2013 Jun;43(6):616-28. doi: 10.1093/jjco/hyt054. Epub 2013 Apr 28.

Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552-62. doi: 10.1016/S1470-2045(13)70093-7. Epub 2013 Apr 16. Erratum In: Lancet Oncol. 2013 Jun;14(7):e254.

Cella D, Escudier B, Rini B, Chen C, Bhattacharyya H, Tarazi J, Rosbrook B, Kim S, Motzer R. Patient-reported outcomes for axitinib vs sorafenib in metastatic renal cell carcinoma: phase III (AXIS) trial. Br J Cancer. 2013 Apr 30;108(8):1571-8. doi: 10.1038/bjc.2013.145. Epub 2013 Apr 11.

Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. doi: 10.1016/S0140-6736(11)61613-9. Epub 2011 Nov 4. Erratum In: Lancet. 2012 Nov 24;380(9856):1818.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00678392
• Other Study ID Numbers: A4061032; AXIS TRIAL; 2008-001451-21 ( EudraCT Number ); AXIS ( Other Identifier: Alias Study Number )
• First Submitted: May 12, 2008
• First Posted: May 15, 2008
• Results First Submitted: February 25, 2012
• Results First Posted: March 27, 2012
• Last Update Posted: January 9, 2019