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

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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)

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

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)

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

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)

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