Trial Outcomes & Findings for Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma (NCT NCT00903175)

Last Updated: 2016-11-08

Results Overview

PFS\_1L based on investigator assessment of radiology data by RECIST 1.0, was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause during or after first-line treatment with everolimus or sunitinib. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

471 participants

Primary outcome timeframe

based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months

Results posted on

2016-11-08

Participant Flow

238 patients were randomized to everolimus as 1st line followed by 2nd line sunitinib. All patients in this group were treated. 233 patients were randomized to the sunitinib as 1st line followed by 2nd line everolimus. However 2 of the 233 patients were not treated in this group.

The trial had a crossover design: first-line therapy until disease progression followed by second-line therapy until disease progression.Patients were randomized 1:1 to either everolimus-sunitinib or sunitinib-everolimus treatment sequence and were stratified by MSKCC risk criteria

Participant milestones

Participant milestones
Measure	Everolimus 1L/Sunitinib 2L everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Period 1 - First Line STARTED	238	231
Period 1 - First Line COMPLETED	161	142
Period 1 - First Line NOT COMPLETED	77	89
Period 2 - Second Line STARTED	128	116
Period 2 - Second Line COMPLETED	79	80
Period 2 - Second Line NOT COMPLETED	49	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus 1L/Sunitinib 2L everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Period 1 - First Line Adverse Event	36	50
Period 1 - First Line Abnormal lab value(s)	0	1
Period 1 - First Line Abnormal test procedure result(s)	1	0
Period 1 - First Line Protocol Violation	3	3
Period 1 - First Line Withdrawal by Subject	8	12
Period 1 - First Line Administrative problems	12	13
Period 1 - First Line Death	17	10
Period 2 - Second Line Missing	1	0
Period 2 - Second Line Adverse Event	16	20
Period 2 - Second Line Withdrawal by Subject	7	5
Period 2 - Second Line Lost to Follow-up	1	0
Period 2 - Second Line Administrative problems	19	9
Period 2 - Second Line Death	5	2

Baseline Characteristics

Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment	Total n=471 Participants Total of all reporting groups
Age, Continuous	61.36 years STANDARD_DEVIATION 12.102 • n=93 Participants	60.84 years STANDARD_DEVIATION 11.627 • n=4 Participants	61.10 years STANDARD_DEVIATION 11.860 • n=27 Participants
Sex/Gender, Customized Female	72 Participants n=93 Participants	57 Participants n=4 Participants	129 Participants n=27 Participants
Sex/Gender, Customized Male	166 Participants n=93 Participants	176 Participants n=4 Participants	342 Participants n=27 Participants

PRIMARY outcome

Timeframe: based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Progression Free Survival First-Line (PFS 1-L)	7.85 Months Interval 5.55 to 8.25	10.71 Months Interval 8.18 to 11.53

SECONDARY outcome

Timeframe: based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to about 56 months

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

PFS-C (1L and 2L study drugs combined) was a composite endpoint which combined both lines of study treatment. It was defined as the time from the date of randomization to the first of the following: date of death due to any cause, or date of the first radiologically documented progression disease during or after the second-line treatment period for patients with a radiologically documented progression disease in the first-line treatment period and who had crossed-over to second-line treatment no more than 6 weeks after progression.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Progression-free Survival Combined (PFS-C)	21.68 Months Interval 15.05 to 26.71	22.18 Months Interval 16.03 to 29.83

SECONDARY outcome

Timeframe: Every 2 months from randomization up to 3 years after last patient randomized

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

Overall survival was defined as the time from date of randomization to date of death due to any cause. The analysis of OS included all deaths in the FAS regardless of when they were observed.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Survival (OS)	22.41 Months Interval 18.6 to 33.28	29.47 Months Interval 22.83 to 33.05

SECONDARY outcome

Timeframe: based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) and was based on investigator assessment of radiology data per RECIST. Participants with best overall response of 'Unknown' were treated as non-responders in the calculation of the ORR. Confirmed CR = at least two determinations of CR at least 4 weeks apart before progression. Confirmed PR = at least two determinations of PR or better at least 4 weeks apart before progression. CR required a disappearance of all target and non-target lesions. PR required at least a 30% decrease in the sum of the longest diameters of all target lesions, taking as a reference the baseline sum of the longest diameters. Radiological assessments : every 12 weeks until disease progression, the start of another antineoplastic therapy or for any other reason.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Response Rate (ORR) - First -Line (1-L) Complete Response (CR)	1 percentage of participants	3 percentage of participants
Overall Response Rate (ORR) - First -Line (1-L) Partial Response (PR)	18 percentage of participants	59 percentage of participants
Overall Response Rate (ORR) - First -Line (1-L) Overall Response Rate (CR + PR)	19 percentage of participants	62 percentage of participants

SECONDARY outcome

Timeframe: based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months

Population: The analysis population corresponds to the patients included in the Full analysis set (i.e. randomized patients analyzed according to the treatment and stratum they were assigned to at randomization) and who achieved a best overall response of CR or PR during the first-line treatment period.

Duration of overall response (CR or PR) applies only to patients whose Best Overall Response (BOR) was Complete Response (CR) or Partial Response (PR) during the first-line treatment period. The start date was the date of first documented response (CR or PR) during the first-line treatment and the end date was the date of the event defined as the first documented progression or death due to underlying cancer during or after the same treatment line.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=19 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=62 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Duration of Response (DoR) - First-Line (1-L)	13.37 Months Interval 8.3 to N/A = Data not estimable due to few number of patient at this time point	17.25 Months Interval 11.4 to N/A = Data not estimable due to few number of patient at this time point

SECONDARY outcome

Timeframe: <=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

The Functional Assessment of Cancer Therapy - Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) is a set of items to assess symptoms experienced by patients with advanced kidney cancer. These symptoms include fatigue, pain, weight loss, dyspnea, cough, fever and hematuria. Each item is scored on a 5-point scale (0 = not at all; 4 = very much). The FKSI-DRS total score ranges from 0 (most severe symptoms) to 36 (no symptoms). Definitive deterioration was defined as a decrease by at least 3 units compared to baseline, with no later increase above this threshold observed during the 1-L of treatment. A single measure reporting a decrease of at least 3 units was considered definitive only if it was the last one available for the patient.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First-line Drug	12.65 Months Interval 7.9 to 19.4	16.66 Months Interval 13.7 to N/A = Data not estimable due to few number of patient at this time point

SECONDARY outcome

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

The Functional Assessment of Cancer Therapy - Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) is a set of items to assess symptoms experienced by patients with advanced kidney cancer. These symptoms include fatigue, pain, weight loss, dyspnea, cough, fever and hematuria. Each item is scored on a 5-point scale (0 = not at all; 4 = very much). The FKSI-DRS total score ranges from 0 (most severe symptoms) to 36 (no symptoms). Definitive deterioration was defined as a decrease by at least 3 units compared to baseline, with no later increase above this threshold observed during the 1-L or 2-L treatment. A single measure reporting a decrease of at least 3 units was considered definitive only if it was the last one available for the patient.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First and Second-line Drugs Combined	14.23 Months Interval 12.0 to 19.4	15.97 Months Interval 13.7 to 20.4

SECONDARY outcome

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items. The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line of treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Time to Definitive Deterioration of the Physical Functioning (PF) Scale of the EORTC QLQ-C30 - by First-Line (1L) Drug	13.47 Months Interval 7.9 to 20.6	14.03 Months Interval 12.1 to 17.7

SECONDARY outcome

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items.The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line or second line treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Time to Definitive Deterioration of the Physical Functioning Scale of the EORTC QLQ-C30 - by First and Second-Line Drugs Combined	12.25 Months Interval 9.5 to 16.3	14.03 Months Interval 12.0 to 17.7

SECONDARY outcome

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items.The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line of treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First-Line Drug	7.92 Months Interval 5.6 to 12.1	12.25 Months Interval 7.9 to 14.1

SECONDARY outcome

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items. The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line or second line treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First and Second-Line Drugs Combined	10.84 Months Interval 7.5 to 13.8	12.71 Months Interval 10.5 to 14.8

SECONDARY outcome

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items.The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line of treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First-Line Drug	9.20 Months Interval 6.2 to 12.6	11.37 Months Interval 9.3 to 13.4

SECONDARY outcome

Population: The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items. The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line or second line treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.

Outcome measures

Outcome measures
Measure	Everolimus 1L/Sunitinib 2L n=238 Participants everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=233 Participants sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First and Second-Line Drugs Combined	11.56 Months Interval 7.9 to 14.1	13.34 Months Interval 10.8 to 15.9

Adverse Events

Everolimus 1L/Sunitinib 2L

Serious events: 139 serious events

Other events: 231 other events

Deaths: 0 deaths

Sunitinib 1L/Everolimus 2L

Serious events: 131 serious events

Other events: 228 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Everolimus 1L/Sunitinib 2L n=238 participants at risk everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=231 participants at risk sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Blood and lymphatic system disorders Anaemia	6.7% 16/238	3.9% 9/231
Blood and lymphatic system disorders Coagulopathy	0.42% 1/238	0.00% 0/231
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/238	0.43% 1/231
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/238	0.43% 1/231
Blood and lymphatic system disorders Lymph node pain	0.00% 0/238	0.43% 1/231
Blood and lymphatic system disorders Lymphopenia	0.00% 0/238	0.43% 1/231
Blood and lymphatic system disorders Thrombocytopenia	0.84% 2/238	3.9% 9/231
Cardiac disorders Acute myocardial infarction	0.42% 1/238	0.87% 2/231
Cardiac disorders Arrhythmia supraventricular	0.00% 0/238	0.43% 1/231
Cardiac disorders Atrial fibrillation	2.9% 7/238	0.00% 0/231
Cardiac disorders Atrial flutter	0.42% 1/238	0.00% 0/231
Cardiac disorders Atrioventricular block second degree	0.42% 1/238	0.00% 0/231
Cardiac disorders Bradycardia	0.00% 0/238	0.43% 1/231
Cardiac disorders Cardiac arrest	0.42% 1/238	0.00% 0/231
Cardiac disorders Cardiac failure	0.00% 0/238	0.87% 2/231
Cardiac disorders Cardiac failure congestive	1.3% 3/238	0.00% 0/231
Cardiac disorders Cardio-respiratory arrest	0.84% 2/238	0.00% 0/231
Cardiac disorders Cardiomyopathy	0.00% 0/238	0.43% 1/231
Cardiac disorders Cardiopulmonary failure	0.00% 0/238	0.87% 2/231
Cardiac disorders Myocardial infarction	1.3% 3/238	1.3% 3/231
Cardiac disorders Myocardial ischaemia	0.42% 1/238	0.43% 1/231
Cardiac disorders Pericardial effusion	0.84% 2/238	0.00% 0/231
Cardiac disorders Sinus bradycardia	0.00% 0/238	0.43% 1/231
Cardiac disorders Sinus tachycardia	0.00% 0/238	0.43% 1/231
Cardiac disorders Stress cardiomyopathy	0.42% 1/238	0.00% 0/231
Cardiac disorders Supraventricular tachycardia	0.42% 1/238	0.00% 0/231
Cardiac disorders Ventricular dysfunction	0.42% 1/238	0.00% 0/231
Ear and labyrinth disorders Vertigo	0.00% 0/238	0.43% 1/231
Endocrine disorders Hypothyroidism	0.00% 0/238	0.87% 2/231
Eye disorders Corneal disorder	0.00% 0/238	0.43% 1/231
Eye disorders Diplopia	0.00% 0/238	0.43% 1/231
Eye disorders Optic ischaemic neuropathy	0.42% 1/238	0.00% 0/231
Eye disorders Visual impairment	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Abdominal distension	0.84% 2/238	0.43% 1/231
Gastrointestinal disorders Abdominal pain	2.5% 6/238	3.5% 8/231
Gastrointestinal disorders Abdominal pain lower	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Abdominal pain upper	1.3% 3/238	0.43% 1/231
Gastrointestinal disorders Anal fissure	0.84% 2/238	0.00% 0/231
Gastrointestinal disorders Anal fistula	0.42% 1/238	0.43% 1/231
Gastrointestinal disorders Ascites	0.84% 2/238	0.87% 2/231
Gastrointestinal disorders Colitis	0.42% 1/238	1.3% 3/231
Gastrointestinal disorders Constipation	0.42% 1/238	1.3% 3/231
Gastrointestinal disorders Diarrhoea	2.5% 6/238	2.2% 5/231
Gastrointestinal disorders Diverticulum	0.42% 1/238	0.00% 0/231
Gastrointestinal disorders Duodenal obstruction	0.42% 1/238	0.00% 0/231
Gastrointestinal disorders Dyspepsia	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Dysphagia	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Enteritis	0.42% 1/238	0.00% 0/231
Gastrointestinal disorders Enterocolitis	0.42% 1/238	0.00% 0/231
Gastrointestinal disorders Gastritis	0.42% 1/238	0.00% 0/231
Gastrointestinal disorders Gastrointestinal erosion	0.42% 1/238	0.00% 0/231
Gastrointestinal disorders Gastrointestinal haemorrhage	1.3% 3/238	0.87% 2/231
Gastrointestinal disorders Gastrointestinal inflammation	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Gingival bleeding	0.42% 1/238	0.00% 0/231
Gastrointestinal disorders Haematemesis	0.42% 1/238	0.43% 1/231
Gastrointestinal disorders Haematochezia	1.3% 3/238	0.00% 0/231
Gastrointestinal disorders Haemorrhoids	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Ileus	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Intestinal obstruction	1.3% 3/238	0.00% 0/231
Gastrointestinal disorders Localised intraabdominal fluid collection	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Melaena	0.42% 1/238	0.43% 1/231
Gastrointestinal disorders Nausea	1.7% 4/238	2.2% 5/231
Gastrointestinal disorders Oesophageal ulcer	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Oral pain	0.42% 1/238	0.00% 0/231
Gastrointestinal disorders Pancreatitis	1.3% 3/238	0.00% 0/231
Gastrointestinal disorders Peritoneal adhesions	0.42% 1/238	0.00% 0/231
Gastrointestinal disorders Rectal haemorrhage	0.42% 1/238	0.43% 1/231
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/238	0.43% 1/231
Gastrointestinal disorders Stomatitis	2.5% 6/238	0.00% 0/231
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.42% 1/238	0.00% 0/231
Gastrointestinal disorders Vomiting	2.1% 5/238	3.5% 8/231
General disorders Asthenia	2.5% 6/238	2.6% 6/231
General disorders Fatigue	2.5% 6/238	2.2% 5/231
General disorders General physical health deterioration	1.3% 3/238	1.7% 4/231
General disorders Generalised oedema	0.42% 1/238	0.00% 0/231
General disorders Impaired healing	0.42% 1/238	0.43% 1/231
General disorders Influenza like illness	0.42% 1/238	0.43% 1/231
General disorders Localised oedema	0.00% 0/238	0.43% 1/231
General disorders Malaise	1.3% 3/238	0.43% 1/231
General disorders Mucous membrane disorder	0.42% 1/238	0.00% 0/231
General disorders Multi-organ failure	0.42% 1/238	0.43% 1/231
General disorders Non-cardiac chest pain	0.84% 2/238	1.3% 3/231
General disorders Oedema peripheral	0.84% 2/238	1.3% 3/231
General disorders Pelvic mass	0.00% 0/238	0.43% 1/231
General disorders Performance status decreased	0.42% 1/238	0.43% 1/231
General disorders Peripheral swelling	0.42% 1/238	0.87% 2/231
General disorders Pyrexia	4.2% 10/238	3.0% 7/231
General disorders Sudden death	0.00% 0/238	0.43% 1/231
Hepatobiliary disorders Cholangitis	0.00% 0/238	0.43% 1/231
Hepatobiliary disorders Cholecystitis	0.84% 2/238	1.7% 4/231
Hepatobiliary disorders Cholecystitis acute	0.84% 2/238	0.00% 0/231
Hepatobiliary disorders Cholelithiasis	0.42% 1/238	0.43% 1/231
Hepatobiliary disorders Haemobilia	0.00% 0/238	0.43% 1/231
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/238	0.43% 1/231
Hepatobiliary disorders Hepatic haemorrhage	0.00% 0/238	0.43% 1/231
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/238	0.43% 1/231
Hepatobiliary disorders Jaundice	0.00% 0/238	0.43% 1/231
Hepatobiliary disorders Jaundice cholestatic	0.42% 1/238	0.43% 1/231
Immune system disorders Drug hypersensitivity	0.42% 1/238	0.00% 0/231
Immune system disorders Hypersensitivity	0.42% 1/238	0.00% 0/231
Infections and infestations Abdominal abscess	0.00% 0/238	0.43% 1/231
Infections and infestations Abscess oral	0.00% 0/238	0.43% 1/231
Infections and infestations Anal abscess	0.00% 0/238	0.43% 1/231
Infections and infestations Aspergillus infection	0.00% 0/238	0.43% 1/231
Infections and infestations Bacteraemia	0.00% 0/238	0.43% 1/231
Infections and infestations Bacterial prostatitis	0.00% 0/238	0.43% 1/231
Infections and infestations Bacterial sepsis	0.42% 1/238	0.00% 0/231
Infections and infestations Bronchitis	0.42% 1/238	0.43% 1/231
Infections and infestations Bronchopneumonia	0.42% 1/238	0.00% 0/231
Infections and infestations Cellulitis	1.3% 3/238	1.3% 3/231
Infections and infestations Clostridium difficile infection	0.42% 1/238	0.00% 0/231
Infections and infestations Diverticulitis	0.42% 1/238	0.87% 2/231
Infections and infestations Empyema	0.42% 1/238	0.00% 0/231
Infections and infestations Endocarditis	0.42% 1/238	0.43% 1/231
Infections and infestations Escherichia sepsis	0.42% 1/238	0.00% 0/231
Infections and infestations Gastrointestinal viral infection	0.00% 0/238	0.43% 1/231
Infections and infestations Hepatitis A	0.42% 1/238	0.00% 0/231
Infections and infestations Herpes zoster	0.42% 1/238	0.00% 0/231
Infections and infestations Infected bites	0.00% 0/238	0.43% 1/231
Infections and infestations Kidney infection	0.00% 0/238	0.43% 1/231
Infections and infestations Localised infection	0.00% 0/238	0.43% 1/231
Infections and infestations Lower respiratory tract infection	0.84% 2/238	0.00% 0/231
Infections and infestations Lung infection	0.84% 2/238	0.43% 1/231
Infections and infestations Pneumonia	7.6% 18/238	6.5% 15/231
Infections and infestations Respiratory tract infection	0.84% 2/238	0.00% 0/231
Infections and infestations Salmonella sepsis	0.00% 0/238	0.43% 1/231
Infections and infestations Sepsis	1.3% 3/238	1.7% 4/231
Infections and infestations Septic shock	1.7% 4/238	0.87% 2/231
Infections and infestations Urinary tract infection	1.3% 3/238	2.2% 5/231
Infections and infestations Wound infection	0.42% 1/238	0.00% 0/231
Infections and infestations Wound sepsis	0.00% 0/238	0.43% 1/231
Injury, poisoning and procedural complications Femoral neck fracture	0.42% 1/238	0.00% 0/231
Injury, poisoning and procedural complications Femur fracture	0.42% 1/238	0.87% 2/231
Injury, poisoning and procedural complications Head injury	0.42% 1/238	0.00% 0/231
Injury, poisoning and procedural complications Heat stroke	0.42% 1/238	0.00% 0/231
Injury, poisoning and procedural complications Hip fracture	0.42% 1/238	0.00% 0/231
Injury, poisoning and procedural complications Humerus fracture	1.3% 3/238	0.00% 0/231
Injury, poisoning and procedural complications Pneumothorax traumatic	0.42% 1/238	0.00% 0/231
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/238	0.43% 1/231
Injury, poisoning and procedural complications Post-traumatic pain	0.00% 0/238	0.43% 1/231
Injury, poisoning and procedural complications Rib fracture	0.84% 2/238	0.00% 0/231
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/238	0.43% 1/231
Injury, poisoning and procedural complications Scar	0.42% 1/238	0.00% 0/231
Injury, poisoning and procedural complications Subdural haematoma	0.42% 1/238	0.43% 1/231
Injury, poisoning and procedural complications Subdural haemorrhage	0.42% 1/238	0.00% 0/231
Investigations Blood creatinine increased	1.3% 3/238	1.3% 3/231
Investigations Body temperature increased	0.42% 1/238	0.00% 0/231
Investigations C-reactive protein increased	0.42% 1/238	0.00% 0/231
Investigations Creatinine renal clearance decreased	0.00% 0/238	0.43% 1/231
Investigations Eastern cooperative oncology group performance status worsened	0.42% 1/238	0.00% 0/231
Investigations Electrocardiogram T wave abnormal	0.00% 0/238	0.43% 1/231
Investigations Gamma-glutamyltransferase increased	0.00% 0/238	0.43% 1/231
Investigations Haemoglobin decreased	0.42% 1/238	0.87% 2/231
Investigations Hepatic enzyme increased	0.00% 0/238	0.43% 1/231
Investigations Troponin	0.00% 0/238	0.43% 1/231
Investigations Troponin I increased	0.42% 1/238	0.00% 0/231
Investigations Troponin increased	0.42% 1/238	0.00% 0/231
Metabolism and nutrition disorders Decreased appetite	1.3% 3/238	0.00% 0/231
Metabolism and nutrition disorders Dehydration	5.5% 13/238	2.6% 6/231
Metabolism and nutrition disorders Diabetes mellitus	0.42% 1/238	0.43% 1/231
Metabolism and nutrition disorders Electrolyte imbalance	0.42% 1/238	0.00% 0/231
Metabolism and nutrition disorders Failure to thrive	0.42% 1/238	0.43% 1/231
Metabolism and nutrition disorders Feeding disorder	0.42% 1/238	0.00% 0/231
Metabolism and nutrition disorders Food intolerance	0.42% 1/238	0.00% 0/231
Metabolism and nutrition disorders Gout	0.42% 1/238	0.00% 0/231
Metabolism and nutrition disorders Hypercalcaemia	0.84% 2/238	2.2% 5/231
Metabolism and nutrition disorders Hyperglycaemia	1.7% 4/238	2.2% 5/231
Metabolism and nutrition disorders Hyperkalaemia	0.42% 1/238	0.43% 1/231
Metabolism and nutrition disorders Hypoalbuminaemia	0.42% 1/238	0.43% 1/231
Metabolism and nutrition disorders Hypocalcaemia	0.42% 1/238	0.00% 0/231
Metabolism and nutrition disorders Hypoglycaemia	0.84% 2/238	0.43% 1/231
Metabolism and nutrition disorders Hypokalaemia	0.42% 1/238	0.43% 1/231
Metabolism and nutrition disorders Hypomagnesaemia	0.42% 1/238	0.00% 0/231
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/238	0.43% 1/231
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/238	0.43% 1/231
Musculoskeletal and connective tissue disorders Arthralgia	0.42% 1/238	0.87% 2/231
Musculoskeletal and connective tissue disorders Back pain	2.1% 5/238	1.3% 3/231
Musculoskeletal and connective tissue disorders Bone pain	0.84% 2/238	0.43% 1/231
Musculoskeletal and connective tissue disorders Flank pain	1.3% 3/238	0.00% 0/231
Musculoskeletal and connective tissue disorders Fracture pain	0.00% 0/238	0.43% 1/231
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/238	0.43% 1/231
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.42% 1/238	0.00% 0/231
Musculoskeletal and connective tissue disorders Myalgia	0.42% 1/238	0.00% 0/231
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/238	0.43% 1/231
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/238	0.87% 2/231
Musculoskeletal and connective tissue disorders Pathological fracture	1.7% 4/238	1.3% 3/231
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.42% 1/238	0.00% 0/231
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/238	0.43% 1/231
Musculoskeletal and connective tissue disorders Vertebral lesion	0.00% 0/238	0.43% 1/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/238	0.43% 1/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial adenocarcinoma	0.00% 0/238	0.43% 1/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumour	0.42% 1/238	0.00% 0/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.42% 1/238	0.00% 0/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangiosis carcinomatosa	0.42% 1/238	0.00% 0/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.42% 1/238	0.00% 0/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.42% 1/238	0.00% 0/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.84% 2/238	0.00% 0/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.42% 1/238	0.43% 1/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/238	0.43% 1/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/238	0.43% 1/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	0.00% 0/238	0.43% 1/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/238	0.43% 1/231
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Waldenstrom's macroglobulinaemia	0.42% 1/238	0.00% 0/231
Nervous system disorders Balance disorder	0.00% 0/238	0.43% 1/231
Nervous system disorders Brain oedema	0.00% 0/238	0.43% 1/231
Nervous system disorders Cerebral haemorrhage	1.3% 3/238	0.43% 1/231
Nervous system disorders Cerebrovascular accident	0.84% 2/238	0.43% 1/231
Nervous system disorders Coma	0.00% 0/238	0.43% 1/231
Nervous system disorders Dizziness	0.42% 1/238	0.43% 1/231
Nervous system disorders Dysgeusia	0.42% 1/238	0.00% 0/231
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/238	0.43% 1/231
Nervous system disorders Haemorrhagic stroke	0.00% 0/238	0.43% 1/231
Nervous system disorders Headache	0.84% 2/238	0.00% 0/231
Nervous system disorders Hemiparesis	0.84% 2/238	0.00% 0/231
Nervous system disorders Hypoaesthesia	0.00% 0/238	0.43% 1/231
Nervous system disorders Intracranial pressure increased	0.00% 0/238	0.43% 1/231
Nervous system disorders Lethargy	0.42% 1/238	0.00% 0/231
Nervous system disorders Loss of consciousness	0.00% 0/238	0.87% 2/231
Nervous system disorders Meningorrhagia	0.00% 0/238	0.43% 1/231
Nervous system disorders Neuralgia	0.00% 0/238	0.43% 1/231
Nervous system disorders Seizure	0.00% 0/238	0.87% 2/231
Nervous system disorders Somnolence	0.00% 0/238	0.43% 1/231
Nervous system disorders Spinal cord compression	1.7% 4/238	1.3% 3/231
Nervous system disorders Status epilepticus	0.00% 0/238	0.43% 1/231
Nervous system disorders Syncope	0.42% 1/238	0.87% 2/231
Nervous system disorders Transient ischaemic attack	0.42% 1/238	0.43% 1/231
Nervous system disorders Visual field defect	0.42% 1/238	0.00% 0/231
Psychiatric disorders Anxiety	0.42% 1/238	0.00% 0/231
Psychiatric disorders Completed suicide	0.42% 1/238	0.00% 0/231
Psychiatric disorders Confusional state	0.42% 1/238	0.87% 2/231
Psychiatric disorders Disorientation	0.00% 0/238	0.43% 1/231
Psychiatric disorders Mental status changes	0.42% 1/238	0.00% 0/231
Psychiatric disorders Panic attack	0.42% 1/238	0.00% 0/231
Renal and urinary disorders Acute kidney injury	4.6% 11/238	4.3% 10/231
Renal and urinary disorders Anuria	0.00% 0/238	0.43% 1/231
Renal and urinary disorders Azotaemia	0.84% 2/238	1.3% 3/231
Renal and urinary disorders Calculus ureteric	0.00% 0/238	0.43% 1/231
Renal and urinary disorders Chronic kidney disease	0.00% 0/238	0.43% 1/231
Renal and urinary disorders Dysuria	0.42% 1/238	0.43% 1/231
Renal and urinary disorders Haematuria	1.7% 4/238	0.00% 0/231
Renal and urinary disorders Hydronephrosis	0.00% 0/238	0.43% 1/231
Renal and urinary disorders Nephrotic syndrome	0.42% 1/238	0.00% 0/231
Renal and urinary disorders Proteinuria	0.00% 0/238	0.43% 1/231
Renal and urinary disorders Renal failure	2.1% 5/238	1.3% 3/231
Renal and urinary disorders Renal vein thrombosis	0.00% 0/238	0.43% 1/231
Renal and urinary disorders Tubulointerstitial nephritis	0.42% 1/238	0.00% 0/231
Renal and urinary disorders Urinary retention	0.84% 2/238	0.00% 0/231
Renal and urinary disorders Urinary tract obstruction	0.42% 1/238	0.00% 0/231
Reproductive system and breast disorders Oedema genital	0.00% 0/238	0.43% 1/231
Reproductive system and breast disorders Pelvic pain	0.00% 0/238	0.43% 1/231
Reproductive system and breast disorders Uterine haemorrhage	0.00% 0/238	0.43% 1/231
Reproductive system and breast disorders Uterine polyp	0.00% 0/238	0.43% 1/231
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/238	0.43% 1/231
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/238	0.43% 1/231
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/238	0.43% 1/231
Respiratory, thoracic and mediastinal disorders Bronchial disorder	0.00% 0/238	0.43% 1/231
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.84% 2/238	0.43% 1/231
Respiratory, thoracic and mediastinal disorders Cough	0.84% 2/238	0.43% 1/231
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.0% 12/238	5.6% 13/231
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.84% 2/238	0.00% 0/231
Respiratory, thoracic and mediastinal disorders Epistaxis	0.84% 2/238	1.3% 3/231
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.7% 4/238	0.00% 0/231
Respiratory, thoracic and mediastinal disorders Hypoxia	0.84% 2/238	0.43% 1/231
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	1.3% 3/238	0.00% 0/231
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.42% 1/238	0.00% 0/231
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.2% 10/238	5.2% 12/231
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.42% 1/238	0.43% 1/231
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.7% 4/238	0.00% 0/231
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.42% 1/238	0.87% 2/231
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/238	1.3% 3/231
Respiratory, thoracic and mediastinal disorders Pulmonary granuloma	0.00% 0/238	0.43% 1/231
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/238	0.43% 1/231
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.42% 1/238	1.3% 3/231
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.5% 6/238	0.43% 1/231
Skin and subcutaneous tissue disorders Angioedema	0.84% 2/238	0.00% 0/231
Skin and subcutaneous tissue disorders Dermatitis	0.42% 1/238	0.00% 0/231
Skin and subcutaneous tissue disorders Generalised erythema	0.42% 1/238	0.00% 0/231
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/238	0.43% 1/231
Vascular disorders Aortic aneurysm	0.00% 0/238	0.43% 1/231
Vascular disorders Aortic dissection	0.00% 0/238	0.43% 1/231
Vascular disorders Hypertension	0.00% 0/238	1.7% 4/231
Vascular disorders Hypertensive crisis	0.00% 0/238	0.87% 2/231
Vascular disorders Hypotension	1.3% 3/238	0.43% 1/231

Other adverse events

Other adverse events
Measure	Everolimus 1L/Sunitinib 2L n=238 participants at risk everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)	Sunitinib 1L/Everolimus 2L n=231 participants at risk sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Blood and lymphatic system disorders Anaemia	31.5% 75/238	30.3% 70/231
Blood and lymphatic system disorders Leukopenia	4.6% 11/238	6.1% 14/231
Blood and lymphatic system disorders Neutropenia	8.8% 21/238	19.5% 45/231
Blood and lymphatic system disorders Thrombocytopenia	15.5% 37/238	25.1% 58/231
Endocrine disorders Hyperthyroidism	1.7% 4/238	6.1% 14/231
Endocrine disorders Hypothyroidism	12.6% 30/238	24.7% 57/231
Eye disorders Periorbital oedema	3.8% 9/238	5.2% 12/231
Gastrointestinal disorders Abdominal discomfort	5.5% 13/238	3.5% 8/231
Gastrointestinal disorders Abdominal distension	8.0% 19/238	6.9% 16/231
Gastrointestinal disorders Abdominal pain	20.6% 49/238	17.7% 41/231
Gastrointestinal disorders Abdominal pain upper	13.4% 32/238	16.5% 38/231
Gastrointestinal disorders Aphthous stomatitis	5.9% 14/238	0.87% 2/231
Gastrointestinal disorders Constipation	27.7% 66/238	29.4% 68/231
Gastrointestinal disorders Diarrhoea	55.0% 131/238	60.6% 140/231
Gastrointestinal disorders Dry mouth	6.7% 16/238	9.5% 22/231
Gastrointestinal disorders Dyspepsia	15.5% 37/238	25.5% 59/231
Gastrointestinal disorders Dysphagia	6.7% 16/238	5.2% 12/231
Gastrointestinal disorders Gastritis	3.4% 8/238	5.6% 13/231
Gastrointestinal disorders Gastrooesophageal reflux disease	5.9% 14/238	12.1% 28/231
Gastrointestinal disorders Mouth ulceration	7.6% 18/238	6.1% 14/231
Gastrointestinal disorders Nausea	47.9% 114/238	54.1% 125/231
Gastrointestinal disorders Oral pain	5.0% 12/238	5.2% 12/231
Gastrointestinal disorders Stomatitis	56.3% 134/238	63.2% 146/231
Gastrointestinal disorders Toothache	6.3% 15/238	3.5% 8/231
Gastrointestinal disorders Vomiting	30.7% 73/238	32.9% 76/231
General disorders Asthenia	18.5% 44/238	27.3% 63/231
General disorders Chills	12.2% 29/238	8.7% 20/231
General disorders Face oedema	6.7% 16/238	8.2% 19/231
General disorders Fatigue	52.1% 124/238	56.7% 131/231
General disorders Non-cardiac chest pain	13.9% 33/238	13.0% 30/231
General disorders Oedema peripheral	33.2% 79/238	25.1% 58/231
General disorders Pain	5.9% 14/238	4.8% 11/231
General disorders Peripheral swelling	6.3% 15/238	4.3% 10/231
General disorders Pyrexia	27.7% 66/238	20.8% 48/231
Infections and infestations Bronchitis	5.0% 12/238	2.6% 6/231
Infections and infestations Influenza	6.7% 16/238	3.5% 8/231
Infections and infestations Nasopharyngitis	10.9% 26/238	7.8% 18/231
Infections and infestations Pneumonia	6.7% 16/238	4.3% 10/231
Infections and infestations Upper respiratory tract infection	10.5% 25/238	16.5% 38/231
Infections and infestations Urinary tract infection	8.8% 21/238	10.0% 23/231
Investigations Alanine aminotransferase increased	6.7% 16/238	7.8% 18/231
Investigations Aspartate aminotransferase increased	5.9% 14/238	5.2% 12/231
Investigations Blood alkaline phosphatase increased	1.7% 4/238	5.2% 12/231
Investigations Blood creatinine increased	14.3% 34/238	16.9% 39/231
Investigations Gamma-glutamyltransferase increased	5.0% 12/238	6.9% 16/231
Investigations Haemoglobin decreased	8.8% 21/238	11.3% 26/231
Investigations Neutrophil count decreased	2.9% 7/238	6.5% 15/231
Investigations Platelet count decreased	2.5% 6/238	7.4% 17/231
Investigations Weight decreased	26.5% 63/238	21.2% 49/231
Metabolism and nutrition disorders Decreased appetite	39.1% 93/238	43.7% 101/231
Metabolism and nutrition disorders Dehydration	8.0% 19/238	10.0% 23/231
Metabolism and nutrition disorders Hypercholesterolaemia	8.0% 19/238	5.2% 12/231
Metabolism and nutrition disorders Hyperglycaemia	17.2% 41/238	13.0% 30/231
Metabolism and nutrition disorders Hyperkalaemia	5.0% 12/238	6.1% 14/231
Metabolism and nutrition disorders Hypertriglyceridaemia	8.8% 21/238	6.5% 15/231
Metabolism and nutrition disorders Hypoalbuminaemia	5.5% 13/238	4.3% 10/231
Metabolism and nutrition disorders Hypokalaemia	5.9% 14/238	5.6% 13/231
Musculoskeletal and connective tissue disorders Arthralgia	21.0% 50/238	19.9% 46/231
Musculoskeletal and connective tissue disorders Back pain	25.2% 60/238	28.6% 66/231
Musculoskeletal and connective tissue disorders Bone pain	3.4% 8/238	6.5% 15/231
Musculoskeletal and connective tissue disorders Flank pain	9.7% 23/238	7.4% 17/231
Musculoskeletal and connective tissue disorders Muscle spasms	7.1% 17/238	4.8% 11/231
Musculoskeletal and connective tissue disorders Muscular weakness	6.3% 15/238	5.6% 13/231
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.3% 15/238	4.8% 11/231
Musculoskeletal and connective tissue disorders Musculoskeletal pain	12.2% 29/238	8.7% 20/231
Musculoskeletal and connective tissue disorders Myalgia	8.0% 19/238	9.5% 22/231
Musculoskeletal and connective tissue disorders Neck pain	4.2% 10/238	6.5% 15/231
Musculoskeletal and connective tissue disorders Pain in extremity	19.7% 47/238	19.0% 44/231
Nervous system disorders Dizziness	16.8% 40/238	13.0% 30/231
Nervous system disorders Dysgeusia	30.7% 73/238	32.5% 75/231
Nervous system disorders Headache	24.4% 58/238	21.6% 50/231
Nervous system disorders Hypoaesthesia	6.7% 16/238	4.3% 10/231
Nervous system disorders Neuropathy peripheral	5.0% 12/238	6.1% 14/231
Nervous system disorders Paraesthesia	5.0% 12/238	5.2% 12/231
Psychiatric disorders Anxiety	8.8% 21/238	8.2% 19/231
Psychiatric disorders Depression	9.2% 22/238	5.6% 13/231
Psychiatric disorders Insomnia	17.2% 41/238	17.7% 41/231
Renal and urinary disorders Dysuria	8.0% 19/238	6.5% 15/231
Renal and urinary disorders Haematuria	5.0% 12/238	7.4% 17/231
Renal and urinary disorders Proteinuria	2.5% 6/238	5.6% 13/231
Respiratory, thoracic and mediastinal disorders Cough	40.3% 96/238	32.9% 76/231
Respiratory, thoracic and mediastinal disorders Dysphonia	5.5% 13/238	2.6% 6/231
Respiratory, thoracic and mediastinal disorders Dyspnoea	28.6% 68/238	24.7% 57/231
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	7.6% 18/238	6.1% 14/231
Respiratory, thoracic and mediastinal disorders Epistaxis	22.3% 53/238	23.4% 54/231
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.0% 12/238	2.2% 5/231
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.8% 28/238	9.5% 22/231
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.9% 14/238	4.8% 11/231
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.7% 16/238	3.0% 7/231
Respiratory, thoracic and mediastinal disorders Productive cough	10.1% 24/238	8.2% 19/231
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	10.9% 26/238	7.4% 17/231
Skin and subcutaneous tissue disorders Alopecia	6.3% 15/238	6.5% 15/231
Skin and subcutaneous tissue disorders Dermatitis	1.7% 4/238	5.2% 12/231
Skin and subcutaneous tissue disorders Dermatitis acneiform	8.4% 20/238	3.9% 9/231
Skin and subcutaneous tissue disorders Dry skin	14.3% 34/238	16.5% 38/231
Skin and subcutaneous tissue disorders Erythema	4.6% 11/238	7.8% 18/231
Skin and subcutaneous tissue disorders Hair colour changes	2.5% 6/238	6.9% 16/231
Skin and subcutaneous tissue disorders Nail disorder	5.5% 13/238	4.3% 10/231
Skin and subcutaneous tissue disorders Night sweats	3.8% 9/238	5.6% 13/231
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	19.3% 46/238	39.8% 92/231
Skin and subcutaneous tissue disorders Pruritus	18.1% 43/238	16.5% 38/231
Skin and subcutaneous tissue disorders Rash	39.9% 95/238	29.0% 67/231
Skin and subcutaneous tissue disorders Swelling face	5.0% 12/238	2.6% 6/231
Skin and subcutaneous tissue disorders Yellow skin	5.0% 12/238	12.1% 28/231
Vascular disorders Hypertension	25.6% 61/238	36.4% 84/231

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER