Kidney Neoplasms
Conditions
Brief summary
To compare the disease free survival time and safety of sunitinib with placebo in adjuvant treatment patients at high risk of recurrent kidney cancer after surgery.
Interventions
DRUGSunitinib malate
sunitinib malate 50 mg PO on schedule 4/2: 4 weeks on, 2 weeks off for 1 year or until disease recurrence or occurrence of a secondary malignancy, significant toxicity, or withdrawal of consent.
OTHERPlacebo
Placebo PO for 1 year on schedule 4/2: 4 weeks on, 2 weeks off or until disease recurrence or occurrence of a secondary malignancy, significant toxicity, or withdrawal of consent
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* High risk renal cancer per modified UISS criteria * Eastern Cooperative Oncology Group (ECOG) 0-2 * predominant clear cell histology * No prior anti-cancer treatment * Kidney tumor has been removed * No evidence of macroscopic disease following surgery
Exclusion criteria
* Histologically undifferentiated carcinomas or collecting duct carcinoma, lymphoma, sarcoma or subjects with metastatic renal sites. * Diagnosis of any second malignancy within the last 5 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been adequately treated with no evidence of recurrent disease for 12 months * known HIV or Hepatitis * any severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS)- Assessed by Blinded Independent Central Review | Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent. Performed 5 years after LSLV or when approximately 258 events survival status, whichever was later. | DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by blinded independent central review (BICR) or investigator assessment for respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for remainder of follow-up period unless the participant had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last participant in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last participant in China Cohort was randomized. |
| DFS- Assessed by the Investigator [Stratified by University of California Los Angeles Integrated Staging System (UISS) High Risk Group-Intent to Treat Population] | Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent. Performed 5 years after LSLV or when approximately 258 events survival status, whichever was later | DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by BICR or investigator assessment for the respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for the remainder of the follow-up period unless the participants had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last participant in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last participant in China Cohort was randomized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later | TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent. |
| Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) | Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which was a 30-item questionnaire with global QoL scale, 5 multi-item functional scales (physical, role, emotional, cognitive, & social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, & pain), and 6 single item symptom scales for other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, & the financial impact of cancer). The questionnaire includes 28 items with 4-point Likert type responses from not at all to very much to assess functioning & symptoms; 2 items with 7-point Likert scales for global health & overall QoL. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented better level for functioning/QoL & more severe for symptoms. |
| PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) | Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which was a 30-item questionnaire with global QoL scale & 5 multi-item functional scales (physical, role, emotional, cognitive, & social functioning). The questionnaire includes 28 items with 4-point Likert type responses from not at all to very much to assess functioning; 2 items with 7-point Likert scales for global health & overall QoL. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented better level for functioning/QoL. |
| Overall Survival (OS)- (Stratified by UISS High Risk Group-Intent to Treat Population) | Every 12 weeks until the time for final analysis (up to data cut-off date: 30 April 2017; maximum exposure:14.9 months) | OS was defined as the time from the date of randomization to the date of death due to any cause. |
| PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) | Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by the EuroQoL Group health status questionnaire (EQ-5D), which was a brief self-administered, validated instrument with 2 parts. In this outcome measure, the first part with 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, & anxiety/depression) was used; a participant was asked to rate each state on a 3-level scale (1=no problem, 2=some problem, & 3=extreme problem); higher levels indicated greater severity/impairment. The published weights allowed the creation of a single summary score called the EQ-5D index, which ranged from -0.594 to 1; low scores represented a higher level of dysfunction & 1 as perfect health. |
| PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) | Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by the EuroQoL Group health status questionnaire (EQ-5D), which was a brief self-administered, validated instrument with 2 parts. The first part assessed the current health state. In this outcome measure, the second part was applied to assess the general health status by using visual analog scale (EQ-5D VAS) which measured participant's self-rated health status on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). |
| Number of Participants With Tolerability Symptoms | Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later | Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent. This table provides the summary of discontinuations de to adverse events. Participants were counted only once in each row. |
| PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) | PROs assessed health-related QoL by using the EORTC QLQ-C30, which was a 30 multi-item symptom scales (fatigue, nausea/vomiting, & pain), and 6 single item symptom scales for other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, & the financial impact of cancer). The questionnaire includes 28 items with 4-point Likert type responses from not at all to very much to assess symptoms. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented more severe symptoms. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later | TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent. |
Countries
Australia, China, Colombia, Czechia, Denmark, France, Germany, Greece, Ireland, Israel, Italy, Malaysia, Mexico, Poland, Slovakia, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Of 674 enrolled participants (615 in global cohort and 59 in china cohort), the results presented refers to the study conducted on 615 (intent-to-treat population) in 21 countries and were randomized to sunitinib and placebo for 9 cycles (1 cycle=42 days).
Pre-assignment details
Screening: From Week 0 (nephrectomy surgery) to Week 11; in this period, echocardiogram/multi-gated acquisition, post-surgery imaging, histopathology, physical examination, laboratory tests, electrocardiogram and concomitant treatment were assessed. Randomization occurred not before 3 weeks post-nephrectomy & not after 12 weeks post-nephrectomy.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib Participants received Sunitinib on 9 6-week cycles on 4/2 dosing schedule: 4 weeks on, 2 weeks off. | 309 |
| Placebo Participants received Placebo on 9 6-week cycles with 4/2 dosing schedule: 4 weeks on, 2 weeks off. | 306 |
| Total | 615 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 67 | 76 |
| Overall Study | Enrolled but not treated | 3 | 2 |
| Overall Study | Lost to Follow-up | 17 | 15 |
| Overall Study | Other | 26 | 18 |
| Overall Study | Participants refused further follow-up | 31 | 30 |
Baseline characteristics
| Characteristic | Sunitinib | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.8 years STANDARD_DEVIATION 10.6 | 57.9 years STANDARD_DEVIATION 10.6 | 57.9 years STANDARD_DEVIATION 10.6 |
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=65 years | 76 Participants | 82 Participants | 158 Participants |
| Age, Customized Between 18 and 65 years | 233 Participants | 224 Participants | 457 Participants |
| Sex/Gender, Customized Female | 87 Participants | 77 Participants | 164 Participants |
| Sex/Gender, Customized Male | 222 Participants | 229 Participants | 451 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 67 / 306 | 76 / 304 |
| other Total, other adverse events | 303 / 306 | 270 / 304 |
| serious Total, serious adverse events | 67 / 306 | 52 / 304 |
Outcome results
Primary
DFS- Assessed by the Investigator [Stratified by University of California Los Angeles Integrated Staging System (UISS) High Risk Group-Intent to Treat Population]
DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by BICR or investigator assessment for the respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for the remainder of the follow-up period unless the participants had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last participant in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last participant in China Cohort was randomized.
Time frame: Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent. Performed 5 years after LSLV or when approximately 258 events survival status, whichever was later
Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | DFS- Assessed by the Investigator [Stratified by University of California Los Angeles Integrated Staging System (UISS) High Risk Group-Intent to Treat Population] | 6.5 Number of years |
| Placebo | DFS- Assessed by the Investigator [Stratified by University of California Los Angeles Integrated Staging System (UISS) High Risk Group-Intent to Treat Population] | 4.5 Number of years |
Comparison: Superiority analysisp-value: 0.07795% CI: [0.643, 1.023]Cox Proportional hazards model
Primary
Disease-free Survival (DFS)- Assessed by Blinded Independent Central Review
DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by blinded independent central review (BICR) or investigator assessment for respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for remainder of follow-up period unless the participant had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last participant in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last participant in China Cohort was randomized.
Time frame: Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent. Performed 5 years after LSLV or when approximately 258 events survival status, whichever was later.
Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Disease-free Survival (DFS)- Assessed by Blinded Independent Central Review | 6.8 Number of years |
| Placebo | Disease-free Survival (DFS)- Assessed by Blinded Independent Central Review | 5.6 Number of years |
Comparison: Superiority analysisp-value: 0.0395% CI: [0.594, 0.975]Cox Proportional hazards model
Secondary
Number of Participants With Tolerability Symptoms
Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent. This table provides the summary of discontinuations de to adverse events. Participants were counted only once in each row.
Time frame: Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later
Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib | Number of Participants With Tolerability Symptoms | Oedema peripheral | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Electrocardiogram ST segment abnormal | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Depression | 0 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Embolism venous | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Dehydration | 2 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Eyelid oedema | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Abdominal pain | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Gastritis haemorrhagic | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Gastrooesophageal reflux disease | 3 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Abdominal pain upper | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Hepatic function abnormal | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Dyspepsia | 2 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Hepatitis acute | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Acute kidney injury | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Hypercreatininaemia | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Stomatitis | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Hypertransaminasaemia | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Ageusia | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Hypothyroidism | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Proteinuria | 2 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Influenza like illness | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Alanine aminotransferase increased | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Mental status changes | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Ejection fraction decreased | 2 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Mucosal inflammation | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Anal inflammation | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Myalgia | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Palmar-plantar erythrodysaesthesia syndrome | 13 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Myocardial infarction | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Thrombocytopenia | 2 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Myocarditis | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Hypertension | 6 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Necrosis | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Aspartate aminotransferase increased | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Nephrotic syndrome | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Asthenia | 4 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Neutropenia | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Upper gastrointestinal haemorrhage | 2 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Fatigue | 3 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Pancytopenia | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Left ventricular dysfunction | 2 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Post procedural infection | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Pulmonary embolism | 3 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Presyncope | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Vomiting | 2 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Pyrexia | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Anal pruritus | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Angina unstable | 0 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Therapeutic response unexpected | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Electrocardiogram QT prolonged | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Tremor | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Atrial fibrillation | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Vena cava thrombosis | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Acute myocardial infarction | 2 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Vertigo | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Agitated depression | 0 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Atrial flutter | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Lethargy | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Brain cancer metastatic | 0 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Diarrhoea | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Hepatitis | 0 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Glossodynia | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Hypersensitivity | 0 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Disease progression | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Metastases to lung | 0 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Mood altered | 0 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Transient ischaemic attack | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Renal impairment | 0 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Dysgeusia | 1 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Tinnitus | 0 Number of participants |
| Sunitinib | Number of Participants With Tolerability Symptoms | Blood creatinine increased | 2 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Tinnitus | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Vertigo | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Metastases to lung | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Pulmonary embolism | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Gastrooesophageal reflux disease | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Ejection fraction decreased | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Left ventricular dysfunction | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Acute myocardial infarction | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Blood creatinine increased | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Dehydration | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Dyspepsia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Proteinuria | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Thrombocytopenia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Upper gastrointestinal haemorrhage | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Vomiting | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Electrocardiogram QT prolonged | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Lethargy | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Transient ischaemic attack | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Depression | 2 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Abdominal pain | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Abdominal pain upper | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Acute kidney injury | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Ageusia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Alanine aminotransferase increased | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Palmar-plantar erythrodysaesthesia syndrome | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Hypertension | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Asthenia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Fatigue | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Anal inflammation | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Anal pruritus | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Aspartate aminotransferase increased | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Atrial fibrillation | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Atrial flutter | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Diarrhoea | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Disease progression | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Dysgeusia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Electrocardiogram ST segment abnormal | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Embolism venous | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Eyelid oedema | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Gastritis haemorrhagic | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Glossodynia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Hepatic function abnormal | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Hepatitis acute | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Hypercreatininaemia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Hypertransaminasaemia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Hypothyroidism | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Influenza like illness | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Mental status changes | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Mucosal inflammation | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Myalgia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Myocardial infarction | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Myocarditis | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Necrosis | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Nephrotic syndrome | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Neutropenia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Oedema peripheral | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Pancytopenia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Post procedural infection | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Presyncope | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Pyrexia | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Stomatitis | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Therapeutic response unexpected | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Tremor | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Vena cava thrombosis | 0 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Agitated depression | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Angina unstable | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Brain cancer metastatic | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Hepatitis | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Hypersensitivity | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Mood altered | 1 Number of participants |
| Placebo | Number of Participants With Tolerability Symptoms | Renal impairment | 1 Number of participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity
TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent.
Time frame: Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later
Population: The As-Treated (AT) population included all participants who received at least 1 dose of study drug with treatment assignments designated according to actual study treatment received. This population was the primary population for evaluating treatment administration/ compliance and safety.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants With Grade 3 or 4 AEs | 189 Number of participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants Discontinued Due to AEs | 86 Number of participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants With Serious Adverse Events (SAEs) | 67 Number of participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants With Dose Reduced Due to AEs | 106 Number of participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants With Grade 5 AEs | 5 Number of participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Temporary Discontinuation Due to AEs | 141 Number of participants |
| Sunitinib | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants With Adverse Events (AEs) | 305 Number of participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Temporary Discontinuation Due to AEs | 40 Number of participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants With Adverse Events (AEs) | 270 Number of participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants With Serious Adverse Events (SAEs) | 52 Number of participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants With Grade 3 or 4 AEs | 61 Number of participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants With Grade 5 AEs | 5 Number of participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants Discontinued Due to AEs | 16 Number of participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | Participants With Dose Reduced Due to AEs | 6 Number of participants |
Secondary
Overall Survival (OS)- (Stratified by UISS High Risk Group-Intent to Treat Population)
OS was defined as the time from the date of randomization to the date of death due to any cause.
Time frame: Every 12 weeks until the time for final analysis (up to data cut-off date: 30 April 2017; maximum exposure:14.9 months)
Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Overall Survival (OS)- (Stratified by UISS High Risk Group-Intent to Treat Population) | NA Year |
| Placebo | Overall Survival (OS)- (Stratified by UISS High Risk Group-Intent to Treat Population) | NA Year |
Comparison: Hazard ratio was based on the Cox Proportional hazards model stratified by UISS High-Risk Group.p-value: 0.66195% CI: [0.67, 1.289]Log-rank test
Secondary
Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores
Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which was a 30-item questionnaire with global QoL scale, 5 multi-item functional scales (physical, role, emotional, cognitive, & social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, & pain), and 6 single item symptom scales for other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, & the financial impact of cancer). The questionnaire includes 28 items with 4-point Likert type responses from not at all to very much to assess functioning & symptoms; 2 items with 7-point Likert scales for global health & overall QoL. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented better level for functioning/QoL & more severe for symptoms.
Time frame: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)
Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or a different drug from that to which they were randomized. Here, 'Number analyzed' signifies the number of participants evaluable at specified time-points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 1 (Baseline) | 74.83 Scores on scale | Standard Error 1.044 |
| Sunitinib | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 2 | 69.71 Scores on scale | Standard Error 1.289 |
| Sunitinib | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 3 | 69.67 Scores on scale | Standard Error 1.278 |
| Sunitinib | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 4 | 66.52 Scores on scale | Standard Error 1.307 |
| Sunitinib | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 5 | 68.34 Scores on scale | Standard Error 1.34 |
| Sunitinib | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 6 | 66.27 Scores on scale | Standard Error 1.396 |
| Sunitinib | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 7 | 67.42 Scores on scale | Standard Error 1.447 |
| Sunitinib | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 8 | 68.33 Scores on scale | Standard Error 1.376 |
| Sunitinib | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 9 | 68.31 Scores on scale | Standard Error 1.556 |
| Sunitinib | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | End of treatment (EOT) | 64.43 Scores on scale | Standard Error 1.367 |
| Placebo | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 8 | 74.49 Scores on scale | Standard Error 1.26 |
| Placebo | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 1 (Baseline) | 75.61 Scores on scale | Standard Error 1.044 |
| Placebo | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 6 | 75.69 Scores on scale | Standard Error 1.172 |
| Placebo | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 2 | 75.49 Scores on scale | Standard Error 1.097 |
| Placebo | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | End of treatment (EOT) | 73.37 Scores on scale | Standard Error 1.264 |
| Placebo | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 3 | 74.09 Scores on scale | Standard Error 1.142 |
| Placebo | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 7 | 73.98 Scores on scale | Standard Error 1.222 |
| Placebo | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 4 | 74.93 Scores on scale | Standard Error 1.109 |
| Placebo | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 9 | 74.06 Scores on scale | Standard Error 1.338 |
| Placebo | Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Cycle 5 | 74.61 Scores on scale | Standard Error 1.179 |
Secondary
PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison
Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which was a 30-item questionnaire with global QoL scale & 5 multi-item functional scales (physical, role, emotional, cognitive, & social functioning). The questionnaire includes 28 items with 4-point Likert type responses from not at all to very much to assess functioning; 2 items with 7-point Likert scales for global health & overall QoL. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented better level for functioning/QoL.
Time frame: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)
Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sunitinib | PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Role | 78.94 Scores on scale |
| Sunitinib | PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Cognitive | 85.50 Scores on scale |
| Sunitinib | PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Emotional | 80.92 Scores on scale |
| Sunitinib | PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Social | 80.62 Scores on scale |
| Sunitinib | PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Physical | 83.54 Scores on scale |
| Placebo | PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Social | 87.99 Scores on scale |
| Placebo | PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Physical | 87.53 Scores on scale |
| Placebo | PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Role | 85.46 Scores on scale |
| Placebo | PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Emotional | 82.97 Scores on scale |
| Placebo | PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Cognitive | 87.43 Scores on scale |
Secondary
PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison
PROs assessed health-related QoL by using the EORTC QLQ-C30, which was a 30 multi-item symptom scales (fatigue, nausea/vomiting, & pain), and 6 single item symptom scales for other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, & the financial impact of cancer). The questionnaire includes 28 items with 4-point Likert type responses from not at all to very much to assess symptoms. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented more severe symptoms.
Time frame: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)
Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sunitinib | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Fatigue | 29.94 Scores on scale |
| Sunitinib | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Appetite Loss | 14.66 Scores on scale |
| Sunitinib | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Dyspnoea | 14.97 Scores on scale |
| Sunitinib | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Constipation | 11.24 Scores on scale |
| Sunitinib | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Nausea and Vomiting | 7.35 Scores on scale |
| Sunitinib | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Diarrhoea | 19.25 Scores on scale |
| Sunitinib | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Insomnia | 22.22 Scores on scale |
| Sunitinib | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Financial Difficulties | 15.12 Scores on scale |
| Sunitinib | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Pain | 21.81 Scores on scale |
| Placebo | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Financial Difficulties | 13.92 Scores on scale |
| Placebo | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Pain | 16.63 Scores on scale |
| Placebo | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Fatigue | 21.74 Scores on scale |
| Placebo | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Nausea and Vomiting | 3.46 Scores on scale |
| Placebo | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Dyspnoea | 11.89 Scores on scale |
| Placebo | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Insomnia | 20.73 Scores on scale |
| Placebo | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Appetite Loss | 4.62 Scores on scale |
| Placebo | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Constipation | 9.83 Scores on scale |
| Placebo | PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | Diarrhoea | 7.25 Scores on scale |
Secondary
PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population
Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by the EuroQoL Group health status questionnaire (EQ-5D), which was a brief self-administered, validated instrument with 2 parts. In this outcome measure, the first part with 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, & anxiety/depression) was used; a participant was asked to rate each state on a 3-level scale (1=no problem, 2=some problem, & 3=extreme problem); higher levels indicated greater severity/impairment. The published weights allowed the creation of a single summary score called the EQ-5D index, which ranged from -0.594 to 1; low scores represented a higher level of dysfunction & 1 as perfect health.
Time frame: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)
Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or a different drug from that to which they were randomized. Here, 'Number analyzed' signifies the number of participants evaluable at specified time-points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 2 | 0.83 Units on a scale | Standard Error 0.011 |
| Sunitinib | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 1 (Baseline) | 0.84 Units on a scale | Standard Error 0.011 |
| Sunitinib | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 3 | 0.80 Units on a scale | Standard Error 0.013 |
| Sunitinib | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 4 | 0.77 Units on a scale | Standard Error 0.014 |
| Sunitinib | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 5 | 0.77 Units on a scale | Standard Error 0.016 |
| Sunitinib | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 6 | 0.78 Units on a scale | Standard Error 0.016 |
| Sunitinib | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 7 | 0.77 Units on a scale | Standard Error 0.016 |
| Sunitinib | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 8 | 0.80 Units on a scale | Standard Error 0.015 |
| Sunitinib | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 9 | 0.81 Units on a scale | Standard Error 0.015 |
| Sunitinib | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | EOT | 0.75 Units on a scale | Standard Error 0.017 |
| Placebo | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 8 | 0.84 Units on a scale | Standard Error 0.013 |
| Placebo | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 6 | 0.85 Units on a scale | Standard Error 0.012 |
| Placebo | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 1 (Baseline) | 0.83 Units on a scale | Standard Error 0.011 |
| Placebo | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 2 | 0.84 Units on a scale | Standard Error 0.011 |
| Placebo | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | EOT | 0.83 Units on a scale | Standard Error 0.015 |
| Placebo | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 3 | 0.82 Units on a scale | Standard Error 0.012 |
| Placebo | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 7 | 0.83 Units on a scale | Standard Error 0.014 |
| Placebo | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 4 | 0.84 Units on a scale | Standard Error 0.011 |
| Placebo | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 9 | 0.85 Units on a scale | Standard Error 0.013 |
| Placebo | PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Cycle 5 | 0.84 Units on a scale | Standard Error 0.013 |
Secondary
PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means
Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by the EuroQoL Group health status questionnaire (EQ-5D), which was a brief self-administered, validated instrument with 2 parts. The first part assessed the current health state. In this outcome measure, the second part was applied to assess the general health status by using visual analog scale (EQ-5D VAS) which measured participant's self-rated health status on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time frame: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year)
Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or a different drug from that to which they were randomized. Here, 'Number analyzed' signifies the number of participants evaluable at specified time-points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 1 (Baseline) | 77.31 Units on a scale | Standard Error 0.999 |
| Sunitinib | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 2 | 74.39 Units on a scale | Standard Error 1.188 |
| Sunitinib | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 3 | 74.20 Units on a scale | Standard Error 1.093 |
| Sunitinib | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 4 | 74.14 Units on a scale | Standard Error 1.118 |
| Sunitinib | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 5 | 73.30 Units on a scale | Standard Error 1.22 |
| Sunitinib | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 6 | 73.51 Units on a scale | Standard Error 1.25 |
| Sunitinib | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 7 | 72.27 Units on a scale | Standard Error 1.267 |
| Sunitinib | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 8 | 73.96 Units on a scale | Standard Error 1.226 |
| Sunitinib | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 9 | 72.93 Units on a scale | Standard Error 1.424 |
| Sunitinib | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | EOT | 71.79 Units on a scale | Standard Error 1.139 |
| Placebo | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 8 | 77.65 Units on a scale | Standard Error 1.213 |
| Placebo | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 1 (Baseline) | 75.67 Units on a scale | Standard Error 1.08 |
| Placebo | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 6 | 78.61 Units on a scale | Standard Error 1.13 |
| Placebo | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 2 | 76.99 Units on a scale | Standard Error 1.08 |
| Placebo | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | EOT | 76.93 Units on a scale | Standard Error 1.283 |
| Placebo | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 3 | 76.85 Units on a scale | Standard Error 1.122 |
| Placebo | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 7 | 77.49 Units on a scale | Standard Error 1.18 |
| Placebo | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 4 | 77.34 Units on a scale | Standard Error 1.115 |
| Placebo | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 9 | 79.02 Units on a scale | Standard Error 1.168 |
| Placebo | PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Cycle 5 | 77.56 Units on a scale | Standard Error 1.212 |
Secondary
Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles)
TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent.
Time frame: Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later
Population: AT population: All participants who received at least 1 dose of study drug with treatment assignments designated according to actual study treatment received.~The numbers of participants analyzed were the participants with any adverse event of special interest (AESI) and that one participant could have reported more than one AESI
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib | Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | Hyperthyroidism | 23.2 Weeks | Standard Deviation 25.95 |
| Sunitinib | Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | Hypothyroidism | 46.9 Weeks | Standard Deviation 75.3 |
| Sunitinib | Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | Thyroid Disorder | 19 Weeks | — |
| Placebo | Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | Hyperthyroidism | 110.8 Weeks | Standard Deviation 146.57 |
| Placebo | Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | Thyroid Mass | 20.4 Weeks | — |
| Placebo | Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | Hypothyroidism | 58.0 Weeks | Standard Deviation 62.06 |
| Placebo | Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | Papillary Thyroid Cancer | 22.1 Weeks | — |
| Placebo | Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | Benign Neoplasm of Thyroid Gland | 35.1 Weeks | — |
| Placebo | Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | Goitre | 305.6 Weeks | Standard Deviation 97.08 |