A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma (METEOR)

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ClinicalTrials.gov Identifier: NCT01865747

Recruitment Status : Completed

First Posted : May 31, 2013

Results First Posted : July 18, 2017

Last Update Posted : April 27, 2021

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Sponsor:

Information provided by (Responsible Party):

Exelixis

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Renal Cell Carcinoma
Interventions	Drug: Cabozantinib tablets Drug: Everolimus (Afinitor) tablets
Enrollment	658

Participant Flow

Recruitment Details	First patient enrolled: 08 August 2013, Data cut off date: 22 May 2015
Pre-assignment Details


Arm/Group Title	Cabozantinib (XL184)	Everolimus (Afinitor)
Arm/Group Description	Cabozantinib (XL184) 60 mg tablet o...	Everolimus (Afinitor) 10 mg tablet ...
Arm/Group Description	Cabozantinib (XL184) 60 mg tablet once daily. Cabozantinib tablets	Everolimus (Afinitor) 10 mg tablet once daily. Everolimus (Afinitor) tablets
Period Title: Overall Study (ITT)
Started ^[1]	330	328
Completed ^[2]	132 ^[3]	73 ^[4]
Not Completed	198	255
Reason Not Completed
Adverse Event	32	31
Clinical Deterioration	29	50
Lack of Efficacy	3	0
Protocol Violation	1	1
Physician Decision	5	2
Withdrawal by Subject	6	11
Sponsor Decision	0	1
Progressive Disease	122	158
Reason Not Provided	0	1
[1] Randomized [2] Continuing study treatment at the time of data cut-off [3] One subject randomized to everolimus arm received cabozantinib discontd due to clin. deterioration [4] Five subjects were randomized but not treated
Period Title: Primary Intent to Treat (PITT)
Started ^[1]	187	188 ^[2]
Completed ^[3]	56	36
Not Completed	131	152
Reason Not Completed
Adverse Event	21	20
Clinical Deterioration	18	29
Lack of Efficacy	2	0
Protocol Violation	1	1
Physician Decision	4	2
Withdrawal by Subject	3	7
Progressive Disease	82	92
Other	0	1
[1] PITT population consisted of the first 375 subjects randomized to received study treatment. [2] Three subjects in the everolimus arm were randomized but not treated. [3] Continuing study treatment at the time of data cut-off

Baseline Characteristics

Arm/Group Title		Cabozantinib (XL184)	Everolimus (Afinitor)	Total
Arm/Group Description		Cabozantinib (XL184) 60 mg tablet o...	Everolimus (Afinitor) 10 mg tablet ...	Total of all reporting groups
Arm/Group Description		Cabozantinib (XL184) 60 mg tablet once daily. Cabozantinib tablets	Everolimus (Afinitor) 10 mg tablet once daily. Everolimus (Afinitor) tablets	Total of all reporting groups
Overall Number of Baseline Participants		330	328	658
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	330 participants	328 participants	658 participants
<65		196	198	394
65 to <75		107	94	201
75 to <85		26	36	62
=>85		1	0	1
Sex/Gender, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	330 participants	328 participants	658 participants
Male		253	241	494
Female		77	86	163
Missing		0	1	1
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
Ethnicity	Number Analyzed	330 participants	328 participants	658 participants
	Hispanic or Latino	19 5.8%	18 5.5%	37 5.6%
	Not Hispanic or Latino	278 84.2%	273 83.2%	551 83.7%
	Unknown or Not Reported	33 10.0%	37 11.3%	70 10.6%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	330 participants	328 participants	658 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	21 6.4%	26 7.9%	47 7.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	6 1.8%	3 0.9%	9 1.4%
	White	269 81.5%	263 80.2%	532 80.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	34 10.3%	36 11.0%	70 10.6%
Geographic Region Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	330 participants	328 participants	658 participants
Europe		167 50.6%	153 46.6%	320 48.6%
North America		118 35.8%	122 37.2%	240 36.5%
Asia Pacific		39 11.8%	47 14.3%	86 13.1%
Latin America		6 1.8%	6 1.8%	12 1.8%
Randomization Stratification Factors per CRF Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	330 participants	328 participants	658 participants
Prior VEGFR-TKI = 1		235 71.2%	229 69.8%	464 70.5%
Prior VEGFR-TKI ≥ 2		95 28.8%	99 30.2%	194 29.5%
MSKCC risk factors = 0		150 45.5%	150 45.7%	300 45.6%
MSKCC risk factors = 1		139 42.1%	135 41.2%	274 41.6%
MSKCC risk factors = 2 or 3		41 12.4%	43 13.1%	84 12.8%
Prior VEGFR-TKI = 1, MSKCC risk factors = 0		102 30.9%	100 30.5%	202 30.7%
Prior VEGFR-TKI = 1, MSKCC risk factors = 1		107 32.4%	103 31.4%	210 31.9%
Prior VEGFR-TKI = 1, MSKCC risk factors = 2 or 3		26 7.9%	26 7.9%	52 7.9%
Prior VEGFR-TKI ≥ 2, MSKCC risk factors =0		48 14.5%	50 15.2%	98 14.9%
Prior VEGFR-TKI ≥ 2, MSKCC risk factors = 1		32 9.7%	32 9.8%	64 9.7%
Prior VEGFR-TKI ≥ 2, MSKCC risk factors = 2 or 3		15 4.5%	17 5.2%	32 4.9%
Karnofsky performance status (KPS) Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	330 participants	328 participants	658 participants
100 (normal activity)		99 30.0%	74 22.6%	173 26.3%
90 (normal activity, minor signs and symptoms)		127 38.5%	142 43.3%	269 40.9%
80 (normal w/effort, minor signs/symptoms)		75 22.7%	90 27.4%	165 25.1%
70 (unable to work, cares for self)		29 8.8%	22 6.7%	51 7.8%
Heng Prognostic Criteria Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	330 participants	328 participants	658 participants
0 adverse factors (favorable risk)		66 20.0%	62 18.9%	128 19.5%
1-2 adverse factors (intermediate risk)		210 63.6%	214 65.2%	424 64.4%
3-6 adverse factors (poor risk)		54 16.4%	52 15.9%	106 16.1%

Outcome Measures

1.Primary Outcome


Title	Progression-free Survival (PFS)
Description	The primary analysis of PFS is the time from randomization to date of ...
Description	The primary analysis of PFS is the time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria) or death due to any cause, whichever occurred first. A Kaplan-Meier analysis was performed to estimate the median duration.
Time Frame	PFS is measured from the date of randomization until the date of first documented disease progression or date of death from any cause as determined by the Independent Radiology Committee (IRC) per RECIST 1.1, assessed for up to 17 months.

Outcome Measure Data

Analysis Population Description

The pre-specified primary analysis of PFS was based on the first 375 randomized subjects (187 cabozantinib and 188 everolimus).


Arm/Group Title	Cabozantinib (XL184)	Everolimus (Afinitor)
Arm/Group Description:	Cabozantinib (XL184) 60 mg tablet o...	Everolimus (Afinitor) 10 mg tablet ...
Arm/Group Description:	Cabozantinib (XL184) 60 mg tablet once daily. Cabozantinib tablets	Everolimus (Afinitor) 10 mg tablet once daily. Everolimus (Afinitor) tablets
Overall Number of Participants Analyzed	187	188
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: months
	7.4 (5.6 to 9.1)	3.8 (3.7 to 5.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cabozantinib (XL184), Everolimus (Afinitor)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	The Log-Rank Test was stratified by the Memorial Sloan-Kettering Cancer Center (MSKCC) group and number of prior VEGFR TKIs.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95% 0.45 to 0.74
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Overall Survival (OS)
Description	Overall Survival (OS) is defined as the time from randomization to the...
Description	Overall Survival (OS) is defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS was calculated using Kaplan-Meier estimates. Interim analyses for OS occurred after 320 deaths (78% of the total OS events needed for final analysis).
Time Frame	OS was measured from the time of randomization until 320 deaths, approximately 28 months

Outcome Measure Data

Analysis Population Description

The Intent to Treat (ITT) population was used and included 658 randomized subjects (330 cabozantinib, 328 everolimus) in the second interim analysis with a cutoff date of 31 December 2015.


Arm/Group Title	Cabozantinib (XL184)	Everolimus (Afinitor)
Arm/Group Description:	Cabozantinib (XL184) 60 mg tablet o...	Everolimus (Afinitor) 10 mg tablet ...
Arm/Group Description:	Cabozantinib (XL184) 60 mg tablet once daily. Cabozantinib tablets	Everolimus (Afinitor) 10 mg tablet once daily. Everolimus (Afinitor) tablets
Overall Number of Participants Analyzed	330	228
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: months
	21.4 ^[1] (18.7 to NA)	16.5 (14.7 to 18.8)

[1]

Too few events to estimate the upper limit of the confidence interval.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cabozantinib (XL184), Everolimus (Afinitor)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0003
	Comments	[Not Specified]
	Method	Log Rank
	Comments	The Log-Rank test was stratified by the Memorial Sloan-Kettering Cancer Center (MSKCC) risk group and number of prior VEGFR TKIs.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95% 0.53 to 0.83
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Objective Response Rate (ORR)
Description	Objective Response Rate (ORR) is the number of participants with a bes...
Description	Objective Response Rate (ORR) is the number of participants with a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. ORR was assessed by the Independent Radiology Committee (IRC) per RECIST 1.1 which was confirmed by a subsequent visit >= 28 days later, and was analyzed in the Intent to Treat (ITT) population at the time of the primary analysis of Progression Free Survival (PFS). The data cutoff date was 22 May 2015.
Time Frame	ORR was assessed at 8 weeks post-randomization, every 8 weeks for 12 months, and every 12 weeks until date of disease progression or death, up to May 2015 (approximately 21 months)

Outcome Measure Data

Analysis Population Description

The analysis of ORR was performed in the ITT population (all randomized: 330 cabozantinib, 328 everolimus) based upon response determined by Independent Radiology Committee (IRC) per RECIST 1.1.


Arm/Group Title	Cabozantinib (XL184)	Everolimus (Afinitor)
Arm/Group Description:	Cabozantinib (XL184) 60 mg tablet o...	Everolimus (Afinitor) 10 mg tablet ...
Arm/Group Description:	Cabozantinib (XL184) 60 mg tablet once daily. Cabozantinib tablets	Everolimus (Afinitor) 10 mg tablet once daily. Everolimus (Afinitor) tablets
Overall Number of Participants Analyzed	330	328
Measure Type: Number Unit of Measure: percentage of participants
	17	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cabozantinib (XL184), Everolimus (Afinitor)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Adverse Events

Time Frame	08 August 2013 - 22 May 2015
Adverse Event Reporting Description	The safety data includes subjects who were randomized and treated. Of 658 patients, 330 were randomized to receive cabozantinib and 328 everolimus. Five subjects in the everolimus arm were randomized but not treated. One subject randomized to the everolimus arm received cabozantinib only as study treatment and was evaluated in the cabozantinib arm for the Safety population (331 cabozantinib, 322 everolimus).

Arm/Group Title	Cabozantinib (XL184)		Everolimus (Afinitor)
Arm/Group Description	Cabozantinib (XL184) 60 mg tablet o...		Everolimus (Afinitor) 10 mg tablet ...
Arm/Group Description	Cabozantinib (XL184) 60 mg tablet once daily. Cabozantinib tablets		Everolimus (Afinitor) 10 mg tablet once daily. Everolimus (Afinitor) tablets
All-Cause Mortality
	Cabozantinib (XL184)		Everolimus (Afinitor)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Cabozantinib (XL184)		Everolimus (Afinitor)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	131/331 (39.58%)		139/322 (43.17%)
Blood and lymphatic system disorders
Abdominal lymphadenopathy ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Anaemia ^† 1	6/331 (1.81%)	6	12/322 (3.73%)	12
Haemorrhagic anaemia ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Lymphadenopathy ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Cardiac disorders
Acute coronary syndrome ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Atrial fibrillation ^† 1	2/331 (0.60%)	2	3/322 (0.93%)	3
Cardiac failure ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Cardiac failure congestive ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Cardiac tamponade ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Conduction disorder ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Myocardial infarction ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Palpitations ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Pericardial effusion ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Ventricular arrhythmia ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Ear and labyrinth disorders
Tinnitus ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Endocrine disorders
Adrenal Insufficiency ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Hypercalcaemia of Malignancy ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Gastrointestinal disorders
Abdominal Pain ^† 1	10/331 (3.02%)	10	2/322 (0.62%)	2
Abdominal Pain Upper ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Anal Fistula ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Ascites ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Colitis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Colitis Ulcerative ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Constipation ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Diarrhoea ^† 1	7/331 (2.11%)	7	2/322 (0.62%)	2
Faecaloma ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Gastric Haemorrhage ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Gastritis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Gastrointestinal Perforation ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Inguinal Hernia ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Intestinal Perforation ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Nausea ^† 1	7/331 (2.11%)	7	2/322 (0.62%)	2
Oesophageal Pain ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Pancreatitis ^† 1	2/331 (0.60%)	2	1/322 (0.31%)	1
Pancreatitis Acute ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Proctitis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Rectal Haemorrhage ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Small Intestine Obstruction ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Small Intestinal Perforation ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Stomatitis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Swollen Tongue ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Upper Gastrointestinal Haemorrhage ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Vomiting ^† 1	6/331 (1.81%)	6	4/322 (1.24%)	4
General disorders
Asthenia ^† 1	4/331 (1.21%)	4	1/322 (0.31%)	1
Death ^† 1	2/331 (0.60%)	2	0/322 (0.00%)	0
Device Occlusion ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Fatigue ^† 1	6/331 (1.81%)	6	5/322 (1.55%)	5
General Physical Health Deterioration ^† 1	4/331 (1.21%)	4	6/322 (1.86%)	6
Generalised Oedema ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Hypothermia ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Local Swelling ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Malaise ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Mucosal Inflammation ^† 1	0/331 (0.00%)	0	2/322 (0.62%)	2
Mutli-Organ Failure ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Non-Cardiac Chest Pain ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Oedema ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Oedema Peripheral ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Pain ^† 1	5/331 (1.51%)	5	4/322 (1.24%)	4
Pyrexia ^† 1	3/331 (0.91%)	3	4/322 (1.24%)	4
Ulcer Haemorrhage ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Hepatobiliary disorders
Bile Duct Obstruction ^† 1	2/331 (0.60%)	2	0/322 (0.00%)	0
Cholangitis ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Cholecystitis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Cholecystitis Acute ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Hepatitis Cholestatic ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Infections and infestations
Abdominal Abscess ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Abscess Neck ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Acute Sinusitis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Anal Abscess ^† 1	2/331 (0.60%)	2	0/322 (0.00%)	0
Anorectal Cellulitis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Appendicitis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Appendicitis Perforated ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Aspergillus Infection ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Bacteraemia ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Bacterial Sepsis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Bronchitis ^† 1	1/331 (0.30%)	1	2/322 (0.62%)	2
Bronchopneumonia ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Device Related Infection ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Diverticulitis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Empyema ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Gastroenteritis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Implant Site Infection ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Infection ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Kidney Infection ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Klebsiella Infection ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Lower Respiratory Tract Infection ^† 1	1/331 (0.30%)	1	3/322 (0.93%)	3
Lung Infection ^† 1	2/331 (0.60%)	2	1/322 (0.31%)	1
Otitis Externa ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Periorbital Cellulitis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Peritonitis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Peritonitis Bacterial ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Pleural Infection ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Pneumocystis Jirovecii Pneumonia ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Pneumonia ^† 1	6/331 (1.81%)	6	13/322 (4.04%)	13
Pyelonephritis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Respiratory Tract Infection ^† 1	0/331 (0.00%)	0	2/322 (0.62%)	2
Sepsis ^† 1	1/331 (0.30%)	1	3/322 (0.93%)	3
Septic Shock ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Skin Infection ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Tuberculosis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Urinary Tract Infection ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Urosepsis ^† 1	2/331 (0.60%)	2	0/322 (0.00%)	0
Viral Pharyngitis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Vulval Cellulitis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Wound Infection ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Injury, poisoning and procedural complications
Acetabulum Fracture ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Contusion ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Extradural Haematoma ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Fall ^† 1	3/331 (0.91%)	3	2/322 (0.62%)	2
Femoral Neck Fracture ^† 1	0/331 (0.00%)	0	2/322 (0.62%)	2
Foreign Body in Eye ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Fracture ^† 1	2/331 (0.60%)	2	0/322 (0.00%)	0
Humerus Fracture ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Incisional Hernia ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Post Procedural Haemorrhage ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Rib Fracture ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Stress Fracture ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Thoracic Vertebral Fracture ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Investigations
Blood Bilirubin Increased ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Blood Cholesterol Increased ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Haemoglobin Decreased ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Weight Decreased ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Metabolism and nutrition disorders
Decreased Appetite ^† 1	2/331 (0.60%)	2	1/322 (0.31%)	1
Dehydration ^† 1	3/331 (0.91%)	3	7/322 (2.17%)	7
Diabetes Mellitus ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Diabetes Mellitus Inadequate Control ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Electrolyte Imbalance ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Hypercalcaemia ^† 1	4/331 (1.21%)	4	4/322 (1.24%)	4
Hyperglycaemia ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Hyperkalaemia ^† 1	2/331 (0.60%)	2	2/322 (0.62%)	2
Hypocalcaemia ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Hypokalaemia ^† 1	2/331 (0.60%)	2	0/322 (0.00%)	0
Hypomagnesaemia ^† 1	4/331 (1.21%)	4	0/322 (0.00%)	0
Hyponatraemia ^† 1	4/331 (1.21%)	4	2/322 (0.62%)	2
Type 2 Diabetes Mellitus ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Back Pain ^† 1	6/331 (1.81%)	6	4/322 (1.24%)	4
Flank Pain ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Haemarthrosis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Lumbar Spinal Stenosis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Musculoskeletal Chest Pain ^† 1	1/331 (0.30%)	1	2/322 (0.62%)	2
Osteolysis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Osteonecrosis of Jaw ^† 1	1/331 (0.30%)	1	2/322 (0.62%)	2
Pain in Extremity ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Pathological Fracture ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Adenocarcinoma of Colon ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Chronic Lymphocytic Leukaemia ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Leiomyoma ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Malignant Melanoma ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Malignant Neoplasm of Orbit ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Metastases to Bone ^† 1	2/331 (0.60%)	2	2/322 (0.62%)	2
Metastases to Central Nervous System ^† 1	1/331 (0.30%)	1	5/322 (1.55%)	5
Metastases to Ovary ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Metastases to Pelvis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Metatases to Spine ^† 1	2/331 (0.60%)	2	2/322 (0.62%)	2
Metatases to Testicle ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Metastatic Pain ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Metastatic Renal Cell Carcinoma ^† 1	2/331 (0.60%)	2	1/322 (0.31%)	1
Renal Cancer ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Renal Cell Carcinoma ^† 1	11/331 (3.32%)	11	11/322 (3.42%)	11
Tumour Associated Fever ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Tumour Thrombosis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Nervous system disorders
Carotid Artery Occlusion ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Carotid Artery Thrombosis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Cerebral Haematoma ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Cerebrovascular Disorder ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Cognitive Disorder ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Convulsion ^† 1	2/331 (0.60%)	2	0/322 (0.00%)	0
Dizziness ^† 1	2/331 (0.60%)	2	1/322 (0.31%)	1
Epilepsy ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Intracranial Venous Sinus Thrombosis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Miller Fisher Syndrome ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Somnolence ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Spinal Cord Compression ^† 1	1/331 (0.30%)	1	4/322 (1.24%)	4
Syncope ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Transient Ischaemic Attack ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Psychiatric disorders
Confusional State ^† 1	2/331 (0.60%)	2	1/322 (0.31%)	1
Delirium ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Renal and urinary disorders
Haematuria ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Renal Failure ^† 1	1/331 (0.30%)	1	2/322 (0.62%)	2
Renal Failure Acute ^† 1	0/331 (0.00%)	0	5/322 (1.55%)	5
Renal Haemorrhage ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Renal Impairment ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Renal pain ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Reproductive system and breast disorders
Pelvic Pain ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Prostatitis ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Cough ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Dyspnoea ^† 1	6/331 (1.81%)	6	13/322 (4.04%)	13
Haemoptysis ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Hydrothorax ^† 1	0/331 (0.00%)	0	3/322 (0.93%)	3
Hypoxia ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Interstitial Lung Disease ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Obstructive Airways Disorder ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Pleural Effusion ^† 1	10/331 (3.02%)	10	6/322 (1.86%)	6
Pneumonia Aspiration ^† 1	0/331 (0.00%)	0	3/322 (0.93%)	3
Pneumonitis ^† 1	0/331 (0.00%)	0	8/322 (2.48%)	8
Pneumothorax ^† 1	4/331 (1.21%)	4	1/322 (0.31%)	1
Pulmonary Embolism ^† 1	6/331 (1.81%)	6	1/322 (0.31%)	1
Pulmonary Haemorrhage ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Respiratory Distress ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Respiratory Failure ^† 1	1/331 (0.30%)	1	1/322 (0.31%)	1
Skin and subcutaneous tissue disorders
Dermatitis Bullous ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Hyperhidrosis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Pruritus ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Rash ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Rash Maculo-Papular ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Vascular disorders
Circulatory Collapse ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Deep Vein Thrombosis ^† 1	4/331 (1.21%)	4	0/322 (0.00%)	0
Hypertension ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Orthostatic Hypotension ^† 1	0/331 (0.00%)	0	1/322 (0.31%)	1
Pelvic Venous Thrombosis ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
Peripheral Ischaemia ^† 1	1/331 (0.30%)	1	0/322 (0.00%)	0
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (17.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cabozantinib (XL184)		Everolimus (Afinitor)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	328/331 (99.09%)		270/322 (83.85%)
Endocrine disorders
Hypothyroidism ^† 1	68/331 (20.54%)	68	2/322 (0.62%)	2
Gastrointestinal disorders
Abdominal Pain ^† 1	50/331 (15.11%)	50	30/322 (9.32%)	30
Abdominal Pain Upper ^† 1	26/331 (7.85%)	26	7/322 (2.17%)	7
Constipation ^† 1	83/331 (25.08%)	83	61/322 (18.94%)	61
Diarrhoea ^† 1	245/331 (74.02%)	245	88/322 (27.33%)	88
Dyspepsia ^† 1	40/331 (12.08%)	40	15/322 (4.66%)	15
Flatulence ^† 1	32/331 (9.67%)	32	6/322 (1.86%)	6
Nausea ^† 1	164/331 (49.55%)	164	89/322 (27.64%)	89
Vomiting ^† 1	105/331 (31.72%)	105	44/322 (13.66%)	44
General disorders
Fatigue ^† 1	185/331 (55.89%)	185	149/322 (46.27%)	149
Investigations
Alanine Aminotransferase Increased ^† 1	53/331 (16.01%)	53	19/322 (5.90%)	19
Aspartate Aminotransferase Increased ^† 1	58/331 (17.52%)	58	18/322 (5.59%)	18
Blood Thyrpod Stimulating Hormone Increased ^† 1	23/331 (6.95%)	23	3/322 (0.93%)	3
Weight Decreased ^† 1	104/331 (31.42%)	104	39/322 (12.11%)	39
Metabolism and nutrition disorders
Decreased Appetite ^† 1	152/331 (45.92%)	152	108/322 (33.54%)	108
Hypomagnesaemia ^† 1	50/331 (15.11%)	50	5/322 (1.55%)	5
Musculoskeletal and connective tissue disorders
Muscle Spasms ^† 1	42/331 (12.69%)	42	16/322 (4.97%)	16
Pain in Extremity ^† 1	46/331 (13.90%)	46	25/322 (7.76%)	25
Nervous system disorders
Dysgeusia ^† 1	78/331 (23.56%)	78	30/322 (9.32%)	30
Respiratory, thoracic and mediastinal disorders
Dysphonia ^† 1	66/331 (19.94%)	66	12/322 (3.73%)	12
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome ^† 1	139/331 (41.99%)	139	19/322 (5.90%)	19
Vascular disorders
Hypertension ^† 1	122/331 (36.86%)	122	23/322 (7.14%)	23
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (17.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Our agreements with investigators vary; constant is our right to review results communications prior to public release, and embargo communications for a period of ≤60 days from submittal for review. We do not prohibit investigators from publishing, but we may require previously undisclosed confidential information, other than study results, to be removed from publications, and single-center publications are postponed until after publication of the trial's primary multicenter publication.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Exelixis Medical Information
Organization:	Exelixis, Inc.
Phone:	855-292-3935
EMail:	druginfo@exelixis.com

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

Denize T, Farah S, Cimadamore A, Flaifel A, Walton E, Sticco-Ivins MA, Labaki C, Braun DA, Sun M, Wang E, Xie W, Choueiri TK, Signoretti S. Biomarkers of Angiogenesis and Clinical Outcomes to Cabozantinib and Everolimus in Patients with Metastatic Renal Cell Carcinoma from the Phase III METEOR Trial. Clin Cancer Res. 2022 Feb 15;28(4):748-755. doi: 10.1158/1078-0432.CCR-21-3088.

Powles T, Choueiri TK, Motzer RJ, Jonasch E, Pal S, Tannir NM, Signoretti S, Kaldate R, Scheffold C, Wang E, Aftab DT, Escudier B, George DJ. Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma. BMC Cancer. 2021 Aug 7;21(1):904. doi: 10.1186/s12885-021-08630-w. Erratum In: BMC Cancer. 2021 Sep 15;21(1):1023.

Donskov F, Motzer RJ, Voog E, Hovey E, Grullich C, Nott LM, Cuff K, Gil T, Jensen NV, Chevreau C, Negrier S, Depenbusch R, Bergmann L, Cornelio I, Champsaur A, Escudier B, Pal S, Powles T, Choueiri TK. Outcomes based on age in the phase III METEOR trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma. Eur J Cancer. 2020 Feb;126:1-10. doi: 10.1016/j.ejca.2019.10.032. Epub 2019 Dec 27.

Flaifel A, Xie W, Braun DA, Ficial M, Bakouny Z, Nassar AH, Jennings RB, Escudier B, George DJ, Motzer RJ, Morris MJ, Powles T, Wang E, Huang Y, Freeman GJ, Choueiri TK, Signoretti S. PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: Analysis of the Randomized Clinical Trials METEOR and CABOSUN. Clin Cancer Res. 2019 Oct 15;25(20):6080-6088. doi: 10.1158/1078-0432.CCR-19-1135. Epub 2019 Aug 1.

Cella D, Escudier B, Tannir NM, Powles T, Donskov F, Peltola K, Schmidinger M, Heng DYC, Mainwaring PN, Hammers HJ, Lee JL, Roth BJ, Marteau F, Williams P, Baer J, Mangeshkar M, Scheffold C, Hutson TE, Pal S, Motzer RJ, Choueiri TK. Quality of Life Outcomes for Cabozantinib Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma: METEOR Phase III Randomized Trial. J Clin Oncol. 2018 Mar 10;36(8):757-764. doi: 10.1200/JCO.2017.75.2170. Epub 2018 Jan 29.

Escudier B, Powles T, Motzer RJ, Olencki T, Aren Frontera O, Oudard S, Rolland F, Tomczak P, Castellano D, Appleman LJ, Drabkin H, Vaena D, Milwee S, Youkstetter J, Lougheed JC, Bracarda S, Choueiri TK. Cabozantinib, a New Standard of Care for Patients With Advanced Renal Cell Carcinoma and Bone Metastases? Subgroup Analysis of the METEOR Trial. J Clin Oncol. 2018 Mar 10;36(8):765-772. doi: 10.1200/JCO.2017.74.7352. Epub 2018 Jan 8.

Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DYC, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ; METEOR investigators. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-927. doi: 10.1016/S1470-2045(16)30107-3. Epub 2016 Jun 5.

Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Geczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ; METEOR Investigators. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. doi: 10.1056/NEJMoa1510016. Epub 2015 Sep 25.

Layout table for additonal information

Responsible Party:	Exelixis
ClinicalTrials.gov Identifier:	NCT01865747
Other Study ID Numbers:	XL184-308
First Submitted:	May 21, 2013
First Posted:	May 31, 2013
Results First Submitted:	April 21, 2017
Results First Posted:	July 18, 2017
Last Update Posted:	April 27, 2021

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