Cancer, Renal Cell Carcinoma (RCC)
Conditions
Keywords
anti-angiogenic agent, renal cell carcinoma, pazopanib, adjuvant therapy, VEGFR inhibitor, localized or locally, advanced renal cell carcinoma (RCC) following nephrectomy, advanced RCC, Cancer
Brief summary
This randomized Phase III study is to evaluate whether pazopanib compared with placebo can prevent or delay recurrence of kidney cancer in patients with moderately high or high risk of developing recurrence after undergoing kidney cancer surgery.
Detailed description
The primary objective of this ongoing study was to evaluate DFS with pazopanib 600 mg daily initial dose as compared with placebo as adjuvant therapy for subjects with localized/locally advanced RCC following nephrectomy. Subjects with locally recurrent renal cell carcinoma (RCC), bilateral RCC, or history of another malignancy were excluded from enrolling in the study. The study was comprised of three successive study periods: 1) the Screening/Baseline period, 2) the study treatment period, and 3) the DFS /OS follow-up period. The Screening/Baseline period had a maximum duration of 12 weeks from the date of nephrectomy to the date of randomization. After a subject met all the eligibility criteria and completed all the required baseline assessments, the subject was randomized in a 1:1 ratio to receive once daily blinded treatment with either pazopanib 600 mg as initial dose or matching placebo based on pre-defined stratification factors. Subjects received continuous daily treatment until completion of the 12-month treatment period, disease recurrence, or unacceptable toxicity/intolerance. Subsequent adjuvant therapies for RCC were not allowed. During the study treatment and DFS follow-up periods, subjects received routine safety and efficacy assessments. The study treatment period was 12 months. Subjects received continuous daily treatment until completion of the 12 month treatment period, disease recurrence, or unacceptable toxicity/intolerance. Subsequent adjuvant therapies for RCC were not allowed. All subjects, regardless of study treatment status (i.e. premature discontinuation or completion of the 12-month treatment), were to be followed with routine imaging assessments and remain blinded until objective evidence of disease recurrence was obtained or until the study achieved the required number of events for the primary endpoint of DFS (319 events). After objective evidence of disease recurrence was obtained, subjects could be unblinded and received the first-line treatment for metastatic RCC per local standard of care. All subjects were off treatment for at least 4 years at the end of study.
Interventions
DRUGplacebo
Placebo matching pazopanib was supplied as aqueous, film-coated tablets containing 200 mg of the free base. The 200 mg tablets were oval-shaped and white in color.
DRUGpazopanib
Pazopanib monohydrochloride salt was supplied as aqueous, film-coated tablets containing 200 mg of the free base. The 200 mg tablets were oval-shaped and white in color.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent * Diagnosis of RCC with clear-cell or predominant clear-cell histology * Subjects with non-metastatic disease (M0) fulfilling any of the following combinations of pathologic staging based on American Joint Committee on Cancer (AJCC) TNM staging version 2010 and Fuhrman nuclear grading. * pT2, G3 or G4, N0; or, * pT3, G any, N0; or, * pT4, G any, N0; or, * pT any, G any, N1 * Fulfill all of the following criteria of disease-free status at baseline: * Had complete gross surgical resection of all RCC via radical or partial nephrectomy using either open or laparoscopic technique. * Baseline imaging of chest, abdomen and pelvis shows no metastasis or residual tumor lesions as confirmed centrally by an independent radiologist. * Received no prior adjuvant or neo-adjuvant treatment for RCC * Recovered from nephrectomy: any surgery related toxicities should be reduced to ≤ grade 1 per NCI Common Terminology Criteria for Adverse Events (CTCAE) (Version 4) * Karnofsky performance scale (KPS) of ≥ 80 * Adequate organ system function
Exclusion criteria
* History of another malignancy. Exception: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible * Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: * Active peptic ulcer disease * Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation * History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment * Active diarrhea of any grade * Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: * Malabsorption syndrome * Major resection of the stomach or small bowel * History of human immunodeficiency virus (HIV) infection * History of active hepatitis * Presence of uncontrolled infection. * History of any one or more of the following cardiovascular conditions within the past 6 months: * Cardiac angioplasty or stenting * Myocardial infarction * Unstable angina * Coronary artery bypass graft surgery * Symptomatic peripheral vascular disease * History of Class III or IV congestive heart failure, as defined by the New York Heart Association Classification of Congestive Heart Failure * History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. * Corrected QT interval (QTc) \> 480 milliseconds (msec) * Poorly controlled hypertension, defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure (BP) must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be \<140/90 mmHg in order for a subject to be eligible for the study (see Section 7.6.2 for instruction on blood pressure measurement and obtaining mean blood pressure values). * Evidence of active bleeding or bleeding diathesis * Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures * Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study treatment and for the duration of the study. * Concurrent therapy given to treat cancer including treatment with an investigational agent or concurrent participation in another clinical trial involving anti-cancer investigational drug. * Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment. * Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or excipients that in the opinion of the investigator contraindicates their participation. * Prior or current use of systemic anti-VEGF inhibitors, cytokines (e.g. interferon, interleukin 2).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) With Pazopanib 600 mg Daily Initial Dose vs. Placebo | approximately 5 years | DFS is defined as the interval between the date of randomization and the earliest date of disease recurrence/metastasis or death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DFS Rates at Yearly Time Points With Pazopanib 600 mg Daily Initial Dose vs. Placebo | yearly for 4 years | — |
| Overall Survival (OS) With Pazopanib 600 mg Daily Initial Dose vs. Placebo | approximately 8.5 years | Overall survival is defined as the time from randomization until death due to any cause. For subjects who did not die, time to death was censored at the last date of known contact. |
| DFS With Pazopanib vs. Placebo | approximately 5 years | DFS is defined as the interval between the date of randomization and the earliest date of disease recurrence/metastasis or death due to any cause. |
| OS With Pazopanib vs. Placebo | approximately 8.5 years | Overall survival is defined as the time from randomization until death due to any cause. For subjects who do not die, time to death will be censored at the last date of known contact. |
| DFS Rates at Yearly Time Points With Pazopanib vs. Placebo | yearly for 4 years | — |
| DFS Pazopanib 800 mg Daily Initial Dose vs. Placebo | approximately 5 years | DFS is defined as the interval between the date of randomization and the earliest date of disease recurrence/metastasis or death due to any cause. |
| OS With Pazopanib 800 mg Daily Initial Dose vs. Placebo | approximately 8.5 years | Overall survival is defined as the time from randomization until death due to any cause. For subjects who did not die, time to death was censored at the last date of known contact. |
| Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU | Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (FKSI-DRS-P, FKSI-DRS-E, FKSI-TSE, FKSI-FWB) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition. DFS: disease-free survival; FU: follow up |
| Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU | Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The DRS-P domain assesses symptoms experienced in the past 7 days. Participants are asked to respond to 12 questions (I have a lack of energy, I feel pain, for example) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 48). A negative mean indicates a worsening of condition. |
| Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | Week 52, 24M DFS FU, 36M DFS FU,48M DFS FU, 54M DFS FU | Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The DRS-E domain assesses symptoms experienced in the past 7 days. Participants are asked to respond to the question of I worry that my condition will get worse by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 4). A negative mean indicates a worsening of condition. |
| Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | Week 52, 24M DFS FU, 36M DFS FU,48M DFS FU, 54M DFS FU | Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The TSE domain assesses side effects experienced in the past 7 days. Participants are asked to respond to 3 questions (I have nausea, I have diarrhea, and I am bothered by side effects of treatment) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 12). A negative mean indicates a worsening of condition. |
| Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | Week 52, 24M DFS FU, 36M DFS FU,48M DFS FU, 54M DFS FU | Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The FWB domain assesses well being in the past 7 days. Participants are asked to respond to 3 questions (I am able to work, I am able to enjoy life, and I am content with the quality of my life now) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 12). A negative mean indicates a worsening of condition. |
| Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU | Health outcome and quality of life measured by EQ-5D thermometer (thermo) score and EQ-5D utility index (UI) score. The EQ-5D is a participant-answered questionnaire measuring 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D has two separate components: utility score and thermometer score. The EQ-5D total utility score ranges from 0 (worst health state) to 1 (perfect health state); 1 reflects the best outcome. The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). |
| Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU | Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (FKSI-DRS-P, FKSI-DRS-E, FKSI-TSE, FKSI-FWB) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition. DFS: disease-free survival; FU: follow up |
| Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU | Health outcome and quality of life measured by NCCN/FACT FKSI-19 questionnaire for ITT ALL. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The DRS-P domain assesses symptoms experienced in the past 7 days. Participants are asked to respond to 12 questions (I have a lack of energy, I feel pain, for example) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 48). A negative mean indicates a worsening of condition. |
| Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU | Health outcome and quality of life measured by NCCN/FACT FKSI-19 questionnaire for ITT ALL. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The DRS-E domain assesses symptoms experienced in the past 7 days. Participants are asked to respond to the question of I worry that my condition will get worse by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 4).A negative mean indicates a worsening of condition. |
| Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU | Health outcome and quality of life measured by NCCN/FACT FKSI-19 questionnaire for ITT ALL. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The TSE domain assesses side effects experienced in the past 7 days. Participants are asked to respond to 3 questions (I have nausea, I have diarrhea, and I am bothered by side effects of treatment) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 12). A negative mean indicates a worsening of condition. |
| Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU | Health outcome and quality of life measured by NCCN/FACT FKSI-19 questionnaire for ITT ALL. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The FWB domain assesses well being in the past 7 days. Participants are asked to respond to 3 questions (I am able to work, I am able to enjoy life, and I am content with the quality of my life now) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 12). A negative mean indicates a worsening of condition. |
| Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU | Health outcome and quality of life measured by using EQ-5D thermometer score and EQ-5D utility index (UI) score. The EQ-5D is a participant-answered questionnaire measuring 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D has two separate components: utility score and thermometer score. The EQ-5D total utility score ranges from 0 (worst health state) to 1 (perfect health state); 1 reflects the best outcome. The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). |
Countries
Argentina, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Luxembourg, Poland, Russia, Slovakia, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study was planned to include 1500 subjects. A total of 1538 subjects were enrolled and analyzed.
Participants by arm
| Arm | Count |
|---|---|
| ITT Pazopanib 800 mg Pazopanib 800 mg daily dose based on safety evaluation. Complete treatment is 12 months. | 198 |
| ITT Placebo 800 mg Placebo matching pazopanib 800 mg daily. Complete treatment is 12 months. | 205 |
| ITT Pazopanib 600 mg Pazopanib 600 mg daily initial dose for 8-12 weeks. Dose can be escalated to 800 mg daily based on safety evaluation. Complete treatment is 12 months. | 571 |
| ITT Placebo 600 mg Placebo matching pazopanib 600 mg daily. Complete treatment is 12 months. | 564 |
| Total | 1,538 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 21 | 16 | 47 | 32 |
| Overall Study | Physician Decision | 5 | 0 | 9 | 5 |
| Overall Study | Withdrawal by Subject | 20 | 19 | 62 | 49 |
Baseline characteristics
| Characteristic | ITT Pazopanib 600 mg | ITT Placebo 600 mg | Total | ITT Placebo 800 mg | ITT Pazopanib 800 mg |
|---|---|---|---|---|---|
| Age, Customized =>18 to <65 | 430 Participants | 406 Participants | 1130 Participants | 140 Participants | 154 Participants |
| Age, Customized =>65 to <75 | 122 Participants | 131 Participants | 344 Participants | 55 Participants | 36 Participants |
| Age, Customized =>75 to <85 | 19 Participants | 27 Participants | 64 Participants | 10 Participants | 8 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 7 Participants | 1 Participants | 9 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 71 Participants | 70 Participants | 195 Participants | 26 Participants | 28 Participants |
| Race/Ethnicity, Customized Missing | 18 Participants | 10 Participants | 29 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 2 Participants | 7 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 471 Participants | 481 Participants | 1298 Participants | 178 Participants | 168 Participants |
| Sex: Female, Male Female | 173 Participants | 164 Participants | 447 Participants | 51 Participants | 59 Participants |
| Sex: Female, Male Male | 398 Participants | 400 Participants | 1091 Participants | 154 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 198 | 0 / 204 | 3 / 568 | 0 / 558 | 4 / 766 | 0 / 762 |
| other Total, other adverse events | 194 / 198 | 147 / 204 | 541 / 568 | 448 / 558 | 735 / 766 | 595 / 762 |
| serious Total, serious adverse events | 44 / 198 | 14 / 204 | 123 / 568 | 54 / 558 | 167 / 766 | 68 / 762 |
Outcome results
Primary
Disease-free Survival (DFS) With Pazopanib 600 mg Daily Initial Dose vs. Placebo
DFS is defined as the interval between the date of randomization and the earliest date of disease recurrence/metastasis or death due to any cause.
Time frame: approximately 5 years
Population: ITT 600 included all randomized subjects with a scheduled initial dose of 600 mg daily.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ITT Pazopanib 600 mg | Disease-free Survival (DFS) With Pazopanib 600 mg Daily Initial Dose vs. Placebo | NA months |
| ITT Placebo 600 mg | Disease-free Survival (DFS) With Pazopanib 600 mg Daily Initial Dose vs. Placebo | NA months |
p-value: 0.164995% CI: [0.699, 1.063]Stratified Log-Rank
Secondary
DFS Pazopanib 800 mg Daily Initial Dose vs. Placebo
DFS is defined as the interval between the date of randomization and the earliest date of disease recurrence/metastasis or death due to any cause.
Time frame: approximately 5 years
Population: ITT 800 included all randomized subjects with a scheduled initial dose of 800 mg daily.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ITT Pazopanib 600 mg | DFS Pazopanib 800 mg Daily Initial Dose vs. Placebo | NA months |
| ITT Placebo 600 mg | DFS Pazopanib 800 mg Daily Initial Dose vs. Placebo | 48.1 months |
p-value: 0.020195% CI: [0.51, 0.943]Stratified Log-Rank
Secondary
DFS Rates at Yearly Time Points With Pazopanib 600 mg Daily Initial Dose vs. Placebo
Time frame: yearly for 4 years
Population: ITT 600 included all randomized subjects with a scheduled initial dose of 600 mg daily.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ITT Pazopanib 600 mg | DFS Rates at Yearly Time Points With Pazopanib 600 mg Daily Initial Dose vs. Placebo | DFS at 1 year | 0.85 Proportion of participants |
| ITT Pazopanib 600 mg | DFS Rates at Yearly Time Points With Pazopanib 600 mg Daily Initial Dose vs. Placebo | DFS at 2 years | 0.72 Proportion of participants |
| ITT Pazopanib 600 mg | DFS Rates at Yearly Time Points With Pazopanib 600 mg Daily Initial Dose vs. Placebo | DFS at 3 years | 0.65 Proportion of participants |
| ITT Placebo 600 mg | DFS Rates at Yearly Time Points With Pazopanib 600 mg Daily Initial Dose vs. Placebo | DFS at 1 year | 0.76 Proportion of participants |
| ITT Placebo 600 mg | DFS Rates at Yearly Time Points With Pazopanib 600 mg Daily Initial Dose vs. Placebo | DFS at 2 years | 0.68 Proportion of participants |
| ITT Placebo 600 mg | DFS Rates at Yearly Time Points With Pazopanib 600 mg Daily Initial Dose vs. Placebo | DFS at 3 years | 0.64 Proportion of participants |
Secondary
DFS Rates at Yearly Time Points With Pazopanib vs. Placebo
Time frame: yearly for 4 years
Population: Total (ITT All) included all randomized subjects, i.e. subjects either with a scheduled initial dose of 600 or 800 mg daily.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ITT Pazopanib 600 mg | DFS Rates at Yearly Time Points With Pazopanib vs. Placebo | DFS at 1 year | 0.85 Proportion of participants |
| ITT Pazopanib 600 mg | DFS Rates at Yearly Time Points With Pazopanib vs. Placebo | DFS at 2 years | 0.72 Proportion of participants |
| ITT Pazopanib 600 mg | DFS Rates at Yearly Time Points With Pazopanib vs. Placebo | DFS at 3 years | 0.65 Proportion of participants |
| ITT Pazopanib 600 mg | DFS Rates at Yearly Time Points With Pazopanib vs. Placebo | DFS at 4 years | 0.62 Proportion of participants |
| ITT Placebo 600 mg | DFS Rates at Yearly Time Points With Pazopanib vs. Placebo | DFS at 4 years | 0.56 Proportion of participants |
| ITT Placebo 600 mg | DFS Rates at Yearly Time Points With Pazopanib vs. Placebo | DFS at 1 year | 0.75 Proportion of participants |
| ITT Placebo 600 mg | DFS Rates at Yearly Time Points With Pazopanib vs. Placebo | DFS at 3 years | 0.61 Proportion of participants |
| ITT Placebo 600 mg | DFS Rates at Yearly Time Points With Pazopanib vs. Placebo | DFS at 2 years | 0.66 Proportion of participants |
Secondary
DFS With Pazopanib vs. Placebo
DFS is defined as the interval between the date of randomization and the earliest date of disease recurrence/metastasis or death due to any cause.
Time frame: approximately 5 years
Population: Total (ITT All) included all randomized subjects, i.e. subjects either with a scheduled initial dose of 600 or 800 mg daily.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ITT Pazopanib 600 mg | DFS With Pazopanib vs. Placebo | NA months |
| ITT Placebo 600 mg | DFS With Pazopanib vs. Placebo | NA months |
p-value: 0.012695% CI: [0.675, 0.954]Stratified Log-Rank
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score
Health outcome and quality of life measured by EQ-5D thermometer (thermo) score and EQ-5D utility index (UI) score. The EQ-5D is a participant-answered questionnaire measuring 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D has two separate components: utility score and thermometer score. The EQ-5D total utility score ranges from 0 (worst health state) to 1 (perfect health state); 1 reflects the best outcome. The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time frame: Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU
Population: ITT 600 included all randomized subjects with a scheduled initial dose of 600 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | Week 52 thermo. score | 0.713 scores on a scale | Standard Error 0.858 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 24M DFS FU thermo. score | 3.356 scores on a scale | Standard Error 0.882 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 36M DFS FU thermo. score | 3.640 scores on a scale | Standard Error 0.882 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 48M DFS FU thermo. score | 3.909 scores on a scale | Standard Error 1.014 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 54M DFS FU thermo. score | 3.076 scores on a scale | Standard Error 1.607 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | Week 52 UI score | -0.019 scores on a scale | Standard Error 0.009 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 24M DFS FU UI score | -0.004 scores on a scale | Standard Error 0.01 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 36M DFS FU UI score | 0.002 scores on a scale | Standard Error 0.011 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 48M DFS FU UI score | -0.002 scores on a scale | Standard Error 0.013 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 54M DFS FU UI score | 0.004 scores on a scale | Standard Error 0.017 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 36M DFS FU UI score | -0.008 scores on a scale | Standard Error 0.011 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | Week 52 thermo. score | 1.430 scores on a scale | Standard Error 0.868 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | Week 52 UI score | -0.001 scores on a scale | Standard Error 0.009 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 24M DFS FU thermo. score | 3.641 scores on a scale | Standard Error 0.877 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 54M DFS FU UI score | -0.013 scores on a scale | Standard Error 0.017 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 36M DFS FU thermo. score | 2.459 scores on a scale | Standard Error 0.883 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 24M DFS FU UI score | 0.016 scores on a scale | Standard Error 0.01 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 48M DFS FU thermo. score | 3.184 scores on a scale | Standard Error 1.015 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 48M DFS FU UI score | 0.008 scores on a scale | Standard Error 0.013 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using EuroQoL-5D (EQ-5D) Score | 54M DFS FU thermo. score | 1.053 scores on a scale | Standard Error 1.56 |
p-value: 0.4995% CI: [-2.751, 1.318]analysis of covariance
p-value: 0.78895% CI: [-2.358, 1.788]analysis of covariance
p-value: 0.26695% CI: [-0.901, 3.262]analysis of covariance
p-value: 0.5795% CI: [-1.779, 3.229]analysis of covariance
p-value: 0.34695% CI: [-2.205, 6.251]analysis of covariance
p-value: 0.11195% CI: [-0.04, 0.004]analysis of covariance
p-value: 0.09495% CI: [-0.044, 0.003]analysis of covariance
p-value: 0.4995% CI: [-0.018, 0.037]analysis of covariance
p-value: 0.5895% CI: [-0.043, 0.024]analysis of covariance
p-value: 0.47395% CI: [-0.029, 0.063]analysis of covariance
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score
Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The DRS-E domain assesses symptoms experienced in the past 7 days. Participants are asked to respond to the question of I worry that my condition will get worse by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 4). A negative mean indicates a worsening of condition.
Time frame: Week 52, 24M DFS FU, 36M DFS FU,48M DFS FU, 54M DFS FU
Population: ITT 600 included all randomized subjects with a scheduled initial dose of 600 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | 24M DFS FU | 0.11 scores on a scale | Standard Error 0.056 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | 48M DFS FU | 0.08 scores on a scale | Standard Error 0.075 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | 36M DFS FU | 0.13 scores on a scale | Standard Error 0.059 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | 54M DFS FU | 0.04 scores on a scale | Standard Error 0.09 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | Week 52 | 0.01 scores on a scale | Standard Error 0.054 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | 54M DFS FU | 0.24 scores on a scale | Standard Error 0.087 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | Week 52 | 0.09 scores on a scale | Standard Error 0.055 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | 24M DFS FU | 0.16 scores on a scale | Standard Error 0.056 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | 36M DFS FU | 0.12 scores on a scale | Standard Error 0.059 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease Related Symptoms-emotional (DRS-E) Domain Score | 48M DFS FU | 0.20 scores on a scale | Standard Error 0.076 |
p-value: 0.23895% CI: [-0.205, 0.051]analysis of covariance
p-value: 0.44295% CI: [-0.185, 0.081]analysis of covariance
p-value: 0.81995% CI: [-0.125, 0.158]analysis of covariance
p-value: 0.22395% CI: [-0.311, 0.073]analysis of covariance
p-value: 0.08595% CI: [-0.435, 0.028]analysis of covariance
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score
Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The DRS-P domain assesses symptoms experienced in the past 7 days. Participants are asked to respond to 12 questions (I have a lack of energy, I feel pain, for example) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 48). A negative mean indicates a worsening of condition.
Time frame: Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU
Population: ITT 600 included all randomized subjects with a scheduled initial dose of 600 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 24M DFS FU | -0.32 scores on a scale | Standard Error 0.273 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 48M DFS FU | -0.67 scores on a scale | Standard Error 0.332 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 36M DFS FU | -0.61 scores on a scale | Standard Error 0.291 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 54M DFS FU | -0.21 scores on a scale | Standard Error 0.449 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | Week 52 | -2.06 scores on a scale | Standard Error 0.278 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 54M DFS FU | -0.55 scores on a scale | Standard Error 0.439 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | Week 52 | -0.44 scores on a scale | Standard Error 0.282 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 24M DFS FU | -0.20 scores on a scale | Standard Error 0.273 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 36M DFS FU | -0.53 scores on a scale | Standard Error 0.294 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 48M DFS FU | -0.46 scores on a scale | Standard Error 0.336 |
p-value: <0.00195% CI: [-2.283, -0.955]analysis of covariance
p-value: 0.72695% CI: [-0.75, 0.522]analysis of covariance
p-value: 0.80195% CI: [-0.789, 0.609]analysis of covariance
p-value: 0.61795% CI: [-1.044, 0.32]analysis of covariance
p-value: 0.56595% CI: [-0.828, 1.51]adjusted for baseline score using mixedm
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score
Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The FWB domain assesses well being in the past 7 days. Participants are asked to respond to 3 questions (I am able to work, I am able to enjoy life, and I am content with the quality of my life now) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 12). A negative mean indicates a worsening of condition.
Time frame: Week 52, 24M DFS FU, 36M DFS FU,48M DFS FU, 54M DFS FU
Population: ITT 600 included all randomized subjects with a scheduled initial dose of 600 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 24M DFS FU | 0.39 scores on a scale | Standard Error 0.168 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 48M DFS FU | 0.51 scores on a scale | Standard Error 0.219 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 36M DFS FU | 0.43 scores on a scale | Standard Error 0.177 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 54M DFS FU | 0.31 scores on a scale | Standard Error 0.308 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | Week 52 | 0.06 scores on a scale | Standard Error 0.153 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 54M DFS FU | 0.59 scores on a scale | Standard Error 0.299 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | Week 52 | 0.33 scores on a scale | Standard Error 0.155 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 24M DFS FU | 0.32 scores on a scale | Standard Error 0.168 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 36M DFS FU | 0.24 scores on a scale | Standard Error 0.178 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 48M DFS FU | 0.42 scores on a scale | Standard Error 0.222 |
p-value: 0.14395% CI: [-0.633, 0.092]analysis of covariance
p-value: 0.73695% CI: [-0.336, 0.475]analysis of covariance
p-value: 0.39795% CI: [-0.247, 0.623]analysis of covariance
p-value: 0.78195% CI: [-0.488, 0.649]analysis of covariance
p-value: 0.50395% CI: [-1.094, 0.539]analysis of covariance
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score
Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The TSE domain assesses side effects experienced in the past 7 days. Participants are asked to respond to 3 questions (I have nausea, I have diarrhea, and I am bothered by side effects of treatment) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 12). A negative mean indicates a worsening of condition.
Time frame: Week 52, 24M DFS FU, 36M DFS FU,48M DFS FU, 54M DFS FU
Population: ITT 600 included all randomized subjects with a scheduled initial dose of 600 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 24M DFS FU | 0.12 scores on a scale | Standard Error 0.061 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 48M DFS FU | -0.04 scores on a scale | Standard Error 0.087 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 36M DFS FU | 0.05 scores on a scale | Standard Error 0.067 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 54M DFS FU | 0.07 scores on a scale | Standard Error 0.089 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | Week 52 | -1.73 scores on a scale | Standard Error 0.101 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 54M DFS FU | 0.09 scores on a scale | Standard Error 0.086 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | Week 52 | -0.34 scores on a scale | Standard Error 0.103 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 24M DFS FU | 0.01 scores on a scale | Standard Error 0.06 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 36M DFS FU | -00.3 scores on a scale | Standard Error 0.067 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 48M DFS FU | -0.01 scores on a scale | Standard Error 0.088 |
p-value: <0.00195% CI: [-1.66, -1.129]analysis of covariance
p-value: 0.08395% CI: [-0.015, 0.249]analysis of covariance
p-value: 0.30795% CI: [-0.074, 0.236]analysis of covariance
p-value: 0.79695% CI: [-0.249, 0.191]analysis of covariance
p-value: 0.88595% CI: [-0.237, 0.205]analysis of covariance
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score
Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (FKSI-DRS-P, FKSI-DRS-E, FKSI-TSE, FKSI-FWB) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition. DFS: disease-free survival; FU: follow up
Time frame: Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU
Population: ITT 600 included all randomized subjects with a scheduled initial dose of 600 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | 24M DFS FU | 0.19 scores on a scale | Standard Error 0.419 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | 48M DFS FU | -0.13 scores on a scale | Standard Error 0.526 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | 36M DFS FU | -0.14 scores on a scale | Standard Error 0.454 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | 54M DFS FU | 0.09 scores on a scale | Standard Error 0.653 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | Week 52 | -3.83 scores on a scale | Standard Error 0.452 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | 54M DFS FU | 0.26 scores on a scale | Standard Error 0.635 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | Week 52 | -0.43 scores on a scale | Standard Error 0.459 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | 24M DFS FU | 0.23 scores on a scale | Standard Error 0.418 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | 36M DFS FU | -0.26 scores on a scale | Standard Error 0.456 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib 600 mg Daily Initial Dose vs. Placebo Assessed Using NCCN/Functional Assessment of Cancer Therapy-Kidney Symptom Index -19 (FACT FKSI-19) Total Score | 48M DFS FU | 0.22 scores on a scale | Standard Error 0.529 |
p-value: <0.00195% CI: [-4.486, -2.307]analysis of covariance
p-value: 0.9395% CI: [-1.003, 0.917]analysis of covariance
p-value: 0.82895% CI: [-0.958, 1.196]analysis of covariance
p-value: 0.60395% CI: [-1.658, 0.964]analysis of covariance
p-value: 0.84195% CI: [-1.843, 1.503]analysis of covariance
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score
Health outcome and quality of life measured by using EQ-5D thermometer score and EQ-5D utility index (UI) score. The EQ-5D is a participant-answered questionnaire measuring 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D has two separate components: utility score and thermometer score. The EQ-5D total utility score ranges from 0 (worst health state) to 1 (perfect health state); 1 reflects the best outcome. The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time frame: Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU
Population: Total (ITT All) included all randomized subjects, i.e. subjects either with a scheduled initial dose of 600 or 800 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | Week 52 thermo. | 0.744 scores on a scale | Standard Error 0.733 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 24M DFS FU thermo. | 4.043 scores on a scale | Standard Error 0.741 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 36M DFS FU thermo. | 3.997 scores on a scale | Standard Error 0.774 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 48M DFS FU thermo. | 4.683 scores on a scale | Standard Error 0.863 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 54M DFS FU thermos. | 3.650 scores on a scale | Standard Error 1.028 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | Week 52 UI score | -0.023 scores on a scale | Standard Error 0.008 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 24M DFS FU UI score | 0.001 scores on a scale | Standard Error 0.008 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 36M DFS FU UI score | 0.004 scores on a scale | Standard Error 0.009 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 48M DFS FU UI score | -0.004 scores on a scale | Standard Error 0.01 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 54M DFS FU UI score | -0.004 scores on a scale | Standard Error 0.012 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 36M DFS FU UI score | -0.004 scores on a scale | Standard Error 0.009 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | Week 52 thermo. | 2.859 scores on a scale | Standard Error 0.742 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | Week 52 UI score | 0.003 scores on a scale | Standard Error 0.008 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 24M DFS FU thermo. | 4.296 scores on a scale | Standard Error 0.743 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 54M DFS FU UI score | 0.003 scores on a scale | Standard Error 0.012 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 36M DFS FU thermo. | 3.150 scores on a scale | Standard Error 0.781 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 24M DFS FU UI score | 0.017 scores on a scale | Standard Error 0.008 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 48M DFS FU thermo. | 4.552 scores on a scale | Standard Error 0.877 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 48M DFS FU UI score | 0.010 scores on a scale | Standard Error 0.01 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using EuroQoL-5D (EQ-5D) Score | 54M DFS FU thermos. | 3.249 scores on a scale | Standard Error 1.043 |
p-value: 0.01895% CI: [-3.872, -0.359]analysis of covariance
p-value: 0.77895% CI: [-2.014, 1.508]analysis of covariance
p-value: 0.37695% CI: [-1.03, 2.724]analysis of covariance
p-value: 0.90595% CI: [-2.032, 2.294]analysis of covariance
p-value: 0.76895% CI: [-2.269, 3.071]analysis of covariance
p-value: 0.00795% CI: [-0.044, -0.007]analysis of covariance
p-value: 0.1395% CI: [-0.036, 0.005]analysis of covariance
p-value: 0.5295% CI: [-0.015, 0.03]analysis of covariance
p-value: 0.27695% CI: [-0.04, 0.011]analysis of covariance
p-value: 0.66595% CI: [-0.037, 0.024]analysis of covariance
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score
Health outcome and quality of life measured by NCCN/FACT FKSI-19 questionnaire for ITT ALL. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The DRS-E domain assesses symptoms experienced in the past 7 days. Participants are asked to respond to the question of I worry that my condition will get worse by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 4).A negative mean indicates a worsening of condition.
Time frame: Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU
Population: Total (ITT All) included all randomized subjects, i.e. subjects either with a scheduled initial dose of 600 or 800 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | 24M DFS FU | 0.15 scores on a scale | Standard Error 0.048 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | 48M DFS FU | 0.16 scores on a scale | Standard Error 0.059 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | 36M DFS FU | 0.19 scores on a scale | Standard Error 0.05 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | 54M DFS FU | 0.16 scores on a scale | Standard Error 0.065 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | Week 52 | 0.04 scores on a scale | Standard Error 0.045 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | 54M DFS FU | 0.17 scores on a scale | Standard Error 0.066 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | Week 52 | 0.14 scores on a scale | Standard Error 0.046 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | 24M DFS FU | 0.19 scores on a scale | Standard Error 0.048 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | 36M DFS FU | 0.15 scores on a scale | Standard Error 0.051 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-emotional (DRS-E) Domain Score | 48M DFS FU | 0.20 scores on a scale | Standard Error 0.06 |
p-value: 0.05995% CI: [-0.211, 0.004]analysis of covariance
p-value: 0.48795% CI: [-0.155, 0.074]analysis of covariance
p-value: 0.88595% CI: [-0.085, 0.16]analysis of covariance
p-value: 0.67695% CI: [-0.183, 0.119]analysis of covariance
p-value: 0.85995% CI: [-0.183, 0.153]analysis of covariance
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score
Health outcome and quality of life measured by NCCN/FACT FKSI-19 questionnaire for ITT ALL. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The DRS-P domain assesses symptoms experienced in the past 7 days. Participants are asked to respond to 12 questions (I have a lack of energy, I feel pain, for example) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 48). A negative mean indicates a worsening of condition.
Time frame: Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU
Population: Total (ITT All) included all randomized subjects, i.e. subjects either with a scheduled initial dose of 600 or 800 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 24M DFS FU | -0.24 scores on a scale | Standard Error 0.232 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 48M DFS FU | -0.25 scores on a scale | Standard Error 0.27 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 36M DFS FU | -0.41 scores on a scale | Standard Error 0.247 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 54M DFS FU | -0.23 scores on a scale | Standard Error 0.329 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | Week 52 | -2.03 scores on a scale | Standard Error 0.235 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 54M DFS FU | -0.68 scores on a scale | Standard Error 0.333 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | Week 52 | -0.51 scores on a scale | Standard Error 0.237 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 24M DFS FU | -0.25 scores on a scale | Standard Error 0.233 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 36M DFS FU | -0.45 scores on a scale | Standard Error 0.25 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Disease-related Symptoms-physical (DRS-P) Domain Score | 48M DFS FU | -0.19 scores on a scale | Standard Error 0.275 |
p-value: <0.00195% CI: [-2.078, -0.952]analysis of covariance
p-value: 0.96195% CI: [-0.534, 0.561]analysis of covariance
p-value: 0.88895% CI: [-0.555, 0.641]analysis of covariance
p-value: 0.85895% CI: [-0.736, 0.614]analysis of covariance
p-value: 0.395% CI: [-0.404, 1.309]analysis of covariance
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score
Health outcome and quality of life measured by NCCN/FACT FKSI-19 questionnaire for ITT ALL. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The FWB domain assesses well being in the past 7 days. Participants are asked to respond to 3 questions (I am able to work, I am able to enjoy life, and I am content with the quality of my life now) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 12). A negative mean indicates a worsening of condition.
Time frame: Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU
Population: Total (ITT All) included all randomized subjects, i.e. subjects either with a scheduled initial dose of 600 or 800 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 24M DFS FU | 0.30 scores on a scale | Standard Error 0.147 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 48M DFS FU | 0.50 scores on a scale | Standard Error 0.179 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 36M DFS FU | 0.3 scores on a scale | Standard Error 0.151 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 54M DFS FU | 0.39 scores on a scale | Standard Error 0.206 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | Week 52 | -0.08 scores on a scale | Standard Error 0.134 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 54M DFS FU | 0.44 scores on a scale | Standard Error 0.208 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | Week 52 | 0.30 scores on a scale | Standard Error 0.136 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 24M DFS FU | 0.41 scores on a scale | Standard Error 0.147 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 36M DFS FU | 0.29 scores on a scale | Standard Error 0.153 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Functional Well Being (FWB) Domain Score | 48M DFS FU | 0.38 scores on a scale | Standard Error 0.183 |
p-value: 0.02295% CI: [-0.695, -0.053]analysis of covariance
p-value: 0.56795% CI: [-0.462, 0.253]analysis of covariance
p-value: 0.70695% CI: [-0.302, 0.446]analysis of covariance
p-value: 0.61295% CI: [-0.343, 0.583]analysis of covariance
p-value: 0.8795% CI: [-0.587, 0.496]analysis of covariance
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score
Health outcome and quality of life measured by NCCN/FACT FKSI-19 questionnaire for ITT ALL. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The TSE domain assesses side effects experienced in the past 7 days. Participants are asked to respond to 3 questions (I have nausea, I have diarrhea, and I am bothered by side effects of treatment) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 12). A negative mean indicates a worsening of condition.
Time frame: Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU
Population: Total (ITT All) included all randomized subjects, i.e. subjects either with a scheduled initial dose of 600 or 800 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 24M DFS FU | 0.12 scores on a scale | Standard Error 0.052 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 48M DFS FU | 0.05 scores on a scale | Standard Error 0.065 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 36M DFS FU | 0.11 scores on a scale | Standard Error 0.057 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 54M DFS FU | 0.09 scores on a scale | Standard Error 0.074 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | Week 52 | -1.86 scores on a scale | Standard Error 0.089 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 54M DFS FU | 0.03 scores on a scale | Standard Error 0.074 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | Week 52 | -0.33 scores on a scale | Standard Error 0.09 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 24M DFS FU | 0.04 scores on a scale | Standard Error 0.052 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 36M DFS FU | -0.02 scores on a scale | Standard Error 0.058 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Scale Treatment Side Effects (TSE) Domain Score | 48M DFS FU | -0.00 scores on a scale | Standard Error 0.066 |
p-value: <0.00195% CI: [-1.769, -1.3]analysis of covariance
p-value: 0.12795% CI: [-0.025, 0.202]analysis of covariance
p-value: 0.06995% CI: [-0.009, 0.255]analysis of covariance
p-value: 0.54495% CI: [-0.11, 0.208]analysis of covariance
p-value: 0.51895% CI: [-0.124, 0.246]analysis of covariance
Secondary
Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score
Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains (FKSI-DRS-P, FKSI-DRS-E, FKSI-TSE, FKSI-FWB) experienced in the past 7 days. Participants are asked to respond to a total of 19 questions regarding symptoms, side effects, and well being by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total score of 0 to 76). A negative mean indicates a worsening of condition. DFS: disease-free survival; FU: follow up
Time frame: Week 52, 24M DFS FU, 36M DFS FU, 48M DFS FU, 54M DFS FU
Population: Total (ITT All) included all randomized subjects, i.e. subjects either with a scheduled initial dose of 600 or 800 mg daily.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | 48M DFS FU | 0.47 scores on a scale | Standard Error 0.421 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | Week 52 | -4.01 scores on a scale | Standard Error 0.385 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | 54M DFS FU | 0.27 scores on a scale | Standard Error 0.505 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | 24M DFS FU | 0.23 scores on a scale | Standard Error 0.361 |
| ITT Pazopanib 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | 36M DFS FU | 0.16 scores on a scale | Standard Error 0.385 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | 24M DFS FU | 0.33 scores on a scale | Standard Error 0.362 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | 36M DFS FU | -0.07 scores on a scale | Standard Error 0.389 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | 48M DFS FU | 0.39 scores on a scale | Standard Error 0.427 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | 54M DFS FU | -0.14 scores on a scale | Standard Error 0.509 |
| ITT Placebo 600 mg | Health-related Quality of Life (HRQoL) With Pazopanib vs. Placebo for ITT ALL Assessed Using National Comprehensive Cancer Network (NCCN)/FACT FKSI-19 Total Score | Week 52 | -0.47 scores on a scale | Standard Error 0.388 |
p-value: <0.00195% CI: [-4.466, -2.606]analysis of covariance
p-value: 0.81295% CI: [-0.942, 0.738]analysis of covariance
p-value: 0.62195% CI: [-0.69, 1.155]analysis of covariance
p-value: 0.87895% CI: [-0.959, 1.122]analysis of covariance
p-value: 0.53395% CI: [-0.887, 1.712]analysis of covariance
Secondary
OS With Pazopanib 800 mg Daily Initial Dose vs. Placebo
Overall survival is defined as the time from randomization until death due to any cause. For subjects who did not die, time to death was censored at the last date of known contact.
Time frame: approximately 8.5 years
Population: ITT 800 included all randomized subjects with a scheduled initial dose of 800 mg daily.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ITT Pazopanib 600 mg | OS With Pazopanib 800 mg Daily Initial Dose vs. Placebo | NA months |
| ITT Placebo 600 mg | OS With Pazopanib 800 mg Daily Initial Dose vs. Placebo | NA months |
p-value: 0.986595% CI: [0.662, 1.521]Stratified Log-Rank
Secondary
OS With Pazopanib vs. Placebo
Overall survival is defined as the time from randomization until death due to any cause. For subjects who do not die, time to death will be censored at the last date of known contact.
Time frame: approximately 8.5 years
Population: Total (ITT All) included all randomized subjects, i.e. subjects either with a scheduled initial dose of 600 or 800 mg daily.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ITT Pazopanib 600 mg | OS With Pazopanib vs. Placebo | NA months |
| ITT Placebo 600 mg | OS With Pazopanib vs. Placebo | NA months |
p-value: 0.995995% CI: [0.796, 1.257]Stratified Log-Rank
Secondary
Overall Survival (OS) With Pazopanib 600 mg Daily Initial Dose vs. Placebo
Overall survival is defined as the time from randomization until death due to any cause. For subjects who did not die, time to death was censored at the last date of known contact.
Time frame: approximately 8.5 years
Population: ITT 600 included all randomized subjects with a scheduled initial dose of 600 mg daily
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ITT Pazopanib 600 mg | Overall Survival (OS) With Pazopanib 600 mg Daily Initial Dose vs. Placebo | 89.5 months |
| ITT Placebo 600 mg | Overall Survival (OS) With Pazopanib 600 mg Daily Initial Dose vs. Placebo | NA months |
p-value: 0.98895% CI: [0.759, 1.311]Stratified Log-Rank
Post Hoc
All Collected Deaths
On treatment deaths were collected from FPFT up to 28 days after study drug discontinuation, for a maximum duration of approx. 13 months (treatment duration ranged from 0 to to 13 months). Deaths post treatment survival follow up were collected after the on-treatment period, up to approx. 8.5 years. Participants who had not died after study drug discontinuation were censored: 82% of participants in the ITT 600 population and 78% of participants in the ITT 800 population.
Time frame: approx. 13 months, approx. 8.5 years
Population: Safety 800: subjects who received at least one dose of study treatment in the ITT 800 population Safety 600: subjects who received at least one dose of study treatment in the ITT 600 population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ITT Pazopanib 600 mg | All Collected Deaths | Deaths post-treatment survival follow-up | 42 participants |
| ITT Pazopanib 600 mg | All Collected Deaths | On-Treatment Deaths | 1 participants |
| ITT Pazopanib 600 mg | All Collected Deaths | Total Deaths | 43 participants |
| ITT Placebo 600 mg | All Collected Deaths | Deaths post-treatment survival follow-up | 46 participants |
| ITT Placebo 600 mg | All Collected Deaths | Total Deaths | 46 participants |
| ITT Placebo 600 mg | All Collected Deaths | On-Treatment Deaths | 0 participants |
| Safety Pazopanib 600 mg | All Collected Deaths | Deaths post-treatment survival follow-up | 99 participants |
| Safety Pazopanib 600 mg | All Collected Deaths | On-Treatment Deaths | 3 participants |
| Safety Pazopanib 600 mg | All Collected Deaths | Total Deaths | 102 participants |
| Safety Placebo 600 mg | All Collected Deaths | Deaths post-treatment survival follow-up | 104 participants |
| Safety Placebo 600 mg | All Collected Deaths | Total Deaths | 104 participants |
| Safety Placebo 600 mg | All Collected Deaths | On-Treatment Deaths | 0 participants |