Trial Outcomes & Findings for A Phase II Study of Axitinib in Patients With Metastatic Renal Cell Cancer Unsuitable for Nephrectomy (NCT NCT01693822)

NCT ID: NCT01693822

Last Updated: 2024-11-21

Results Overview

The proportion of study participants alive and progression free at 6 months (day 1 week 25 visit). Progression will be measured from the date of study entry (registration date) until the first date of either death or confirmed progressive disease according to RECIST v1.1 (https://recist.eortc.org/recist-1-1-2/). Patients alive and free from progression will be censored at the date of last follow-up. The proportion of patients progression free at 6 months will be reported with 95% confidence interval. In addition, progression free survival will be presented using the Kaplan Meier product limit method with median progression free survival reported. A blinded central review of CT scans will be conducted for verification purposes.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 65 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2024-11-21

Participant Flow

Participant milestones

Measure	Axitinib Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Axitinib: Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.
Overall Study STARTED	65
Overall Study COMPLETED	65
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Axitinib n=65 Participants Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Axitinib: Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.
Age, Continuous	63.5 years n=65 Participants
Age, Customized 40-49 years	8 Participants n=65 Participants
Age, Customized 50-59 years	19 Participants n=65 Participants
Age, Customized 60-69 years	26 Participants n=65 Participants
Age, Customized 70+ years	12 Participants n=65 Participants
Sex: Female, Male Female	22 Participants n=65 Participants
Sex: Female, Male Male	43 Participants n=65 Participants
Histological type Clear cell	62 Participants n=65 Participants
Histological type Clear cell and chromophobe	2 Participants n=65 Participants
Histological type Clear cell and sarcomatoid component	1 Participants n=65 Participants
Fuhrman grade G1 - inconspicuous nucleoli at ×400 magnification and basophilic (low-grade)	2 Participants n=65 Participants
Fuhrman grade G2 - clearly visible nucleoli at ×400 magnification and eosinophilic (low-grade)	26 Participants n=65 Participants
Fuhrman grade G3 - clearly visible nucleoli at ×100 magnification (high grade)	21 Participants n=65 Participants
Fuhrman grade G4 - extreme pleomorphism or rhabdoid and/or sarcomatoid morphology (high grade and most aggressive)	2 Participants n=65 Participants
Fuhrman grade Unobtainable	14 Participants n=65 Participants
Motzer Score Intermediate risk (1-2 risk factors)	50 Participants n=65 Participants
Motzer Score High risk (3+ risk factors)	15 Participants n=65 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Reporting group

The proportion of study participants alive and progression free at 6 months (day 1 week 25 visit). Progression will be measured from the date of study entry (registration date) until the first date of either death or confirmed progressive disease according to RECIST v1.1 (https://recist.eortc.org/recist-1-1-2/). Patients alive and free from progression will be censored at the date of last follow-up. The proportion of patients progression free at 6 months will be reported with 95% confidence interval. In addition, progression free survival will be presented using the Kaplan Meier product limit method with median progression free survival reported. A blinded central review of CT scans will be conducted for verification purposes.

Outcome measures

Measure

Axitinib n=65 Participants Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Axitinib: Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.

Freedom From Progression at 6 Months

58.5 Percentage Interval 45.6 to 70.6

SECONDARY outcome

Timeframe: From registration, during treatment and up to 30 days after treatment discontinuation. Patients remain on treatment until disease progression assessed up to 106 months.

Population: Reporting group

Best overall response (one of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) throughout the treatment period according to RECIST v1.1 (https://recist.eortc.org/recist-1-1-2/).

Outcome measures

Measure	Axitinib n=65 Participants Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Axitinib: Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.
Best Overall Response Complete Response (CR)	1 Participants
Best Overall Response Partial Response (PR)	19 Participants
Best Overall Response Stable Disease (SD)	29 Participants
Best Overall Response Progressive Disease (PD)	16 Participants

SECONDARY outcome

Timeframe: From the date of registration until first date of either death or confirmed progressive disease from any cause, whichever came first, assessed up to 106 months.

Population: Reporting group

Progression-free survival (PFS) will be measured from the date of registration until first date of either death or confirmed progressive disease according to RECIST 1.1. Time to last follow-up will be used if patient has not progressed or died and PFS time for the patient will be considered censored. A Kaplan Meier graph and median survival time will be presented.

Outcome measures

Measure

Axitinib n=65 Participants Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Axitinib: Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.

Progression Free Survival

63.1 Months Interval 50.2 to 74.7

SECONDARY outcome

Timeframe: From the date of registration until the date of death due to any cause, up to 106 months.

Population: Reporting group

Overall survival will be measured from the date of registration until the date of death due to any cause. Time to last follow-up will be used if patient has not died and survival time for the patient will be considered censored.

Outcome measures

Measure

Axitinib n=65 Participants Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Axitinib: Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.

Overall Survival

19.7 Months Interval 9.2 to 37.2

SECONDARY outcome

Timeframe: Treatment duration (at least 4 weekly, and again at disease progression), up to 106 months.

Population: This population contains all patients who received at least one dose of axitinib.

Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.

Outcome measures

Measure	Axitinib n=64 Participants Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Axitinib: Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.
Safety and Toxicity of Axitinib (by NCI CTC Grading Version 4) Total subjects affected by serious adverse events subjects affected / exposed	26 Participants
Safety and Toxicity of Axitinib (by NCI CTC Grading Version 4) number of deaths (all causes)	62 Participants
Safety and Toxicity of Axitinib (by NCI CTC Grading Version 4) number of deaths resulting from adverse events	3 Participants

SECONDARY outcome

Timeframe: Study duration (assessed by clinician over treatment duration), up to 106 months.

Population: Reporting group

The proportion of patients who undergo nephrectomy following registration as a result of treatment with axitinib will be reported with 95% confidence intervals.

Outcome measures

Measure

Axitinib n=65 Participants Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Axitinib: Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.

Number of Patients Who Become Suitable for Nephrectomy as a Consequence of Therapy With Axitinib

9 Participants

Adverse Events

Axitinib

Serious events: 26 serious events

Other events: 64 other events

Deaths: 62 deaths

Serious adverse events

Measure	Axitinib n=64 participants at risk Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Axitinib: Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Vascular disorders Circulatory collapse	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Vascular disorders Hypotension	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
General disorders Chills	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
General disorders Fatigue	4.7% 3/64 • Number of events 3 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
General disorders Pain	4.7% 3/64 • Number of events 3 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
General disorders Pyrexia	6.2% 4/64 • Number of events 4 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.2% 4/64 • Number of events 4 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Respiratory, thoracic and mediastinal disorders Productive cough	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Psychiatric disorders Mental disorder	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Psychiatric disorders Blood calcium increased	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Injury, poisoning and procedural complications Fall	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Injury, poisoning and procedural complications Wound dehiscence	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Cardiac disorders Acute coronary syndrome	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Cardiac disorders Acute myocardial infarction	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Cardiac disorders Atrial fibrillation	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Cardiac disorders Myocardial ischaemia	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Nervous system disorders Dizziness	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Nervous system disorders Partial seizures	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Blood and lymphatic system disorders Thrombocytopenia	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Diarrhoea	4.7% 3/64 • Number of events 3 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Haematemesis	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Hypophagia	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Nausea	3.1% 2/64 • Number of events 2 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Renal and urinary disorders Haematuria	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Renal and urinary disorders Nephrotic syndrome	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Renal and urinary disorders Urinary retention	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Renal and urinary disorders Urinary tract infection	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Renal and urinary disorders Urosepsis	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Endocrine disorders Adrenal insufficiency	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Arthralgia	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Back pain	6.2% 4/64 • Number of events 4 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Bone pain	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Muscular weakness	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Infections and infestations Infection	3.1% 2/64 • Number of events 2 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Infections and infestations Lower respiratory tract infection	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Infections and infestations Pneumonia	4.7% 3/64 • Number of events 3 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Infections and infestations Sepsis	3.1% 2/64 • Number of events 2 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Infections and infestations Urinary tract infection	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Infections and infestations Wound infection	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Metabolism and nutrition disorders Decreased appetite	3.1% 2/64 • Number of events 2 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Metabolism and nutrition disorders Hyperkalaemia	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Metabolism and nutrition disorders Hyponatraemia	1.6% 1/64 • Number of events 1 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.

Other adverse events

Measure	Axitinib n=64 participants at risk Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg. Axitinib: Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities. Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy. Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day. Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.
Vascular disorders Hot flush	6.2% 4/64 • Number of events 19 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Vascular disorders Hypertension	93.8% 60/64 • Number of events 881 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
General disorders Chest pain	17.2% 11/64 • Number of events 15 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
General disorders Fatigue	95.3% 61/64 • Number of events 651 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
General disorders Mucosal inflammation	50.0% 32/64 • Number of events 157 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
General disorders Oedema peripheral	6.2% 4/64 • Number of events 9 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
General disorders Pain	17.2% 11/64 • Number of events 50 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
General disorders Pyrexia	15.6% 10/64 • Number of events 13 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Reproductive system and breast disorders Vaginal haemorrhage	6.2% 4/64 • Number of events 15 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Respiratory, thoracic and mediastinal disorders Cough	39.1% 25/64 • Number of events 105 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Respiratory, thoracic and mediastinal disorders Dysphonia	40.6% 26/64 • Number of events 190 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Respiratory, thoracic and mediastinal disorders Dyspnoea	45.3% 29/64 • Number of events 145 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Respiratory, thoracic and mediastinal disorders Epistaxis	14.1% 9/64 • Number of events 22 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Psychiatric disorders Insomnia	26.6% 17/64 • Number of events 99 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Psychiatric disorders Mood altered	9.4% 6/64 • Number of events 9 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Alanine aminotransferase increased	6.2% 4/64 • Number of events 8 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Blood alkaline phosphatase increased	15.6% 10/64 • Number of events 22 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Blood creatinine decreased	6.2% 4/64 • Number of events 11 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Blood creatinine increased	12.5% 8/64 • Number of events 23 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Blood lactate dehydrogenase increased	10.9% 7/64 • Number of events 25 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Blood magnesium decreased	6.2% 4/64 • Number of events 13 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Gamma-glutamyltransferase increased	12.5% 8/64 • Number of events 26 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Lymphocyte count decreased	17.2% 11/64 • Number of events 49 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Platelet count increased	9.4% 6/64 • Number of events 8 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Prothrombin time prolonged	6.2% 4/64 • Number of events 9 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Investigations Weight decreased	43.8% 28/64 • Number of events 166 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Injury, poisoning and procedural complications Wound complication	6.2% 4/64 • Number of events 4 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Nervous system disorders Dizziness	18.8% 12/64 • Number of events 44 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Nervous system disorders Dysgeusia	43.8% 28/64 • Number of events 167 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Nervous system disorders Headache	25.0% 16/64 • Number of events 35 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Nervous system disorders Neuralgia	7.8% 5/64 • Number of events 7 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Nervous system disorders Neuropathy peripheral	7.8% 5/64 • Number of events 8 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Nervous system disorders Paraesthesia	9.4% 6/64 • Number of events 28 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Blood and lymphatic system disorders Anaemia	20.3% 13/64 • Number of events 24 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Abdominal pain	40.6% 26/64 • Number of events 131 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Constipation	42.2% 27/64 • Number of events 189 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Diarrhoea	59.4% 38/64 • Number of events 434 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Dry mouth	9.4% 6/64 • Number of events 7 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Dyspepsia	23.4% 15/64 • Number of events 56 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Mouth ulceration	6.2% 4/64 • Number of events 14 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Nausea	59.4% 38/64 • Number of events 181 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Oral pain	9.4% 6/64 • Number of events 25 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Stomatitis	34.4% 22/64 • Number of events 90 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Gastrointestinal disorders Vomiting	37.5% 24/64 • Number of events 79 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Skin and subcutaneous tissue disorders Alopecia	12.5% 8/64 • Number of events 12 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Skin and subcutaneous tissue disorders Dry skin	31.2% 20/64 • Number of events 54 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Skin and subcutaneous tissue disorders Night sweats	10.9% 7/64 • Number of events 31 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Skin and subcutaneous tissue disorders Palmar-plantar Erythrodysesthesia syndrome	35.9% 23/64 • Number of events 217 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Skin and subcutaneous tissue disorders Pruritus	7.8% 5/64 • Number of events 10 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Skin and subcutaneous tissue disorders Rash	31.2% 20/64 • Number of events 85 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Renal and urinary disorders Proteinuria	59.4% 38/64 • Number of events 234 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Renal and urinary disorders Renal pain	7.8% 5/64 • Number of events 11 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Endocrine disorders Hyperthyroidism	6.2% 4/64 • Number of events 4 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Endocrine disorders Hypothyroidism	43.8% 28/64 • Number of events 194 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Arthralgia	35.9% 23/64 • Number of events 204 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Back pain	57.8% 37/64 • Number of events 236 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Bone pain	10.9% 7/64 • Number of events 16 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Flank pain	7.8% 5/64 • Number of events 7 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Joint swelling	6.2% 4/64 • Number of events 17 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Muscle spasms	6.2% 4/64 • Number of events 4 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Muscular weakness	31.2% 20/64 • Number of events 56 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	14.1% 9/64 • Number of events 16 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	20.3% 13/64 • Number of events 71 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	6.2% 4/64 • Number of events 8 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Myalgia	14.1% 9/64 • Number of events 33 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Musculoskeletal and connective tissue disorders Pain in extremity	32.8% 21/64 • Number of events 101 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Infections and infestations Lower respiratory tract infection	10.9% 7/64 • Number of events 13 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Infections and infestations Nasopharyngitis	6.2% 4/64 • Number of events 4 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Infections and infestations Urinary tract infection	6.2% 4/64 • Number of events 10 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Metabolism and nutrition disorders Decreased appetite	70.3% 45/64 • Number of events 243 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Metabolism and nutrition disorders Hypercalcaemia	6.2% 4/64 • Number of events 7 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Metabolism and nutrition disorders Hyperglycaemia	9.4% 6/64 • Number of events 41 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Metabolism and nutrition disorders Hypoalbuminemia	20.3% 13/64 • Number of events 34 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.
Metabolism and nutrition disorders Hyponatraemia	9.4% 6/64 • Number of events 17 • AEs were assessed up to 28 days after the patient discontinued study drug, up to 106 months.. All-Cause Mortality was assessed up to 106 months. Both were assessed from the date of registration. Progression of the malignancy was not reported as a serious adverse event. Hospitalisation due to signs and symptoms of malignancy progression was not reported as a serious adverse event. Occurrences are counted as any subject reporting a particular AE at a visit where toxicity was assessed.

Additional Information

Professor Judith Bliss (Director of ICR-CTSU)

Institute of Cancer Research, Clinical Trials and Statistics Unit (ICR-CTSU)

Phone: +44 0208 722 4297

Email: apredict-icrctsu@icr.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee There is an agreement between principal investigators and the Sponsor (or its agents) that restricts the PIs rights to discuss or publish trial results after the trial is completed.
• Publication restrictions are in place

Restriction type: OTHER