Trial Outcomes & Findings for Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma. (NCT NCT01035229)

NCT ID: NCT01035229

Last Updated: 2016-09-22

Results Overview

OS was defined as the time from the date of randomization to the date of death from any cause. The comparison of OS between the 2 arms was done using a stratified log-rank test at one-sided 2.5% level of significance.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 546 participants
• Primary outcome timeframe: When 454 OS events were observed
• Results posted on: 2016-09-22

Participant Flow

763 patients screened, 546 randomized. At 14Jun2013 data cut-off (final analysis), 3 pts in everolimus arm, 6 in placebo arm were still on treatment. Of 9 pts, 3 receiving placebo discontinued due to disease progression. Remaining 6 completed study due to sponsor's decision to end study after final results. The LPLV was 15Oct2013.

Participant milestones

Measure	Everolimus + Best Supportive Care (BSC) Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Overall Study STARTED	362	184
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	362	184

Reasons for withdrawal

Measure	Everolimus + Best Supportive Care (BSC) Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Overall Study Adverse Event	61	14
Overall Study Withdrawal by Subject	20	7
Overall Study Lost to Follow-up	1	0
Overall Study Administrative problems	1	1
Overall Study Death	13	5
Overall Study New cancer therapy	2	0
Overall Study Protocol Violation	0	2
Overall Study Sponsor's decision to end study	3	3
Overall Study Disease Progression	261	152

Baseline Characteristics

Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma.

Baseline characteristics by cohort

Measure	Everolimus + Best Supportive Care (BSC) n=362 Participants Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care n=184 Participants Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.	Total n=546 Participants Total of all reporting groups
Age, Continuous	65.1 Years STANDARD_DEVIATION 11.70 • n=5 Participants	64.2 Years STANDARD_DEVIATION 10.41 • n=7 Participants	64.8 Years STANDARD_DEVIATION 11.28 • n=5 Participants
Age, Customized < 35 years	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Age, Customized >=35 - <55 years	48 Participants n=5 Participants	31 Participants n=7 Participants	79 Participants n=5 Participants
Age, Customized >=55 - <65 years	100 Participants n=5 Participants	61 Participants n=7 Participants	161 Participants n=5 Participants
Age, Customized >= 65 years	207 Participants n=5 Participants	91 Participants n=7 Participants	298 Participants n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	24 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	303 Participants n=5 Participants	160 Participants n=7 Participants	463 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	192 Participants n=5 Participants	110 Participants n=7 Participants	302 Participants n=5 Participants
Race/Ethnicity, Customized Black	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Asian	137 Participants n=5 Participants	58 Participants n=7 Participants	195 Participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	27 Participants n=5 Participants	12 Participants n=7 Participants	39 Participants n=5 Participants
Weight	69.6 kg STANDARD_DEVIATION 15.62 • n=5 Participants	71.3 kg STANDARD_DEVIATION 17.71 • n=7 Participants	70.2 kg STANDARD_DEVIATION 16.35 • n=5 Participants
Height	167.9 cm STANDARD_DEVIATION 8.66 • n=5 Participants	169.2 cm STANDARD_DEVIATION 8.84 • n=7 Participants	168.3 cm STANDARD_DEVIATION 8.73 • n=5 Participants
BMI	24.5 kg/m^2 STANDARD_DEVIATION 4.64 • n=5 Participants	24.8 kg/m^2 STANDARD_DEVIATION 4.99 • n=7 Participants	24.6 kg/m^2 STANDARD_DEVIATION 4.76 • n=5 Participants

PRIMARY outcome

Timeframe: When 454 OS events were observed

Population: The Full Analysis Set (FAS) comprised all randomized patients.

OS was defined as the time from the date of randomization to the date of death from any cause. The comparison of OS between the 2 arms was done using a stratified log-rank test at one-sided 2.5% level of significance.

Outcome measures

Measure	Everolimus + Best Supportive Care (BSC) n=362 Participants Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care n=184 Participants Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Overall Survival (OS)	7.56 Months Interval 6.7 to 8.74	7.33 Months Interval 6.28 to 8.74

SECONDARY outcome

Timeframe: Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient

Population: The Full Analysis Set (FAS) comprised all randomized patients.

TTP was defined as the time from the date of randomization to the date of the first documented radiologic confirmation of disease progression. Since the study did not meet the primary objective, TTP was not formally tested.

Outcome measures

Measure	Everolimus + Best Supportive Care (BSC) n=362 Participants Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care n=184 Participants Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Time to Tumor Progression (TTP)	2.96 Months Interval 2.79 to 4.01	2.60 Months Interval 1.48 to 2.83

SECONDARY outcome

Timeframe: Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient

Population: The Full Analysis Set (FAS) comprised all randomized patients.

DCR is defined as the proportion of participants with a best objective response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST. The BOR was the best response recorded from the start of the treatment until disease progression. CR is disappearance of all target lesions; PR is at least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD is at least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.

Outcome measures

Measure	Everolimus + Best Supportive Care (BSC) n=362 Participants Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care n=184 Participants Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Percentage of Participants With Disease Control Rate (DCR)	56.1 Percentage of Participants	45.1 Percentage of Participants

SECONDARY outcome

Timeframe: Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient.

Population: The Full Analysis Set (FAS) comprised all randomized patients.

Change in Eastern Cooperative Oncology Group (ECOG) were assessed by time to definitive performance status deterioration by at least one category on the ECOG scale. Deterioration was considered definitive if no improvement in the ECOG PS was observed at a subsequent measurement. ECOG PS: 0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2=Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; 5=Dead

Outcome measures

Measure	Everolimus + Best Supportive Care (BSC) n=362 Participants Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care n=184 Participants Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Time to Definitive Deterioration of ECOG Performance Score (PS) Score	4.27 Months Interval 3.32 to 4.86	4.47 Months Interval 3.02 to 6.08

SECONDARY outcome

Timeframe: Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient.

Population: The Full Analysis Set (FAS) comprised all randomized patients.

The primary quality of life endpoint was the time to definitive 5% deterioration from baseline in the global health status/quality of life scale of the EORTC QLQ-C30 questionnaire. Definitive deterioration by at least 5% is defined as a decrease in score by at least 5% compared to baseline, with no later observed increase above this threshold. The EORTC quality of life questionnaire (QLQ) is an integrated system for assessing the healthrelated quality of life (QoL) of cancer patients participating in international clinical trials. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Outcome measures

Measure	Everolimus + Best Supportive Care (BSC) n=362 Participants Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care n=184 Participants Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Time to Definitive Deterioration of EORTC QLQ-C30 Scores	2.86 Months Interval 2.66 to 4.11	3.45 Months Interval 2.79 to 4.17

SECONDARY outcome

Timeframe: Until all patients have disease progression or leave study due to intolerable adverse events - Estimate of 1 year for each patient.

Population: Safety Set consisted of all patients who received at least one dose of study treatment with a valid postbaseline assessment. All PK analyses were based on the Safety Set.

Cmin is the pre-dose blood concentration at steady-state (ng/mL). Pre-dose (Cmin) blood samples were collected from all patients in both arms at Visit 3. Steady-state for the Cmin sample was defined as continuous administration of the same dose in the last 4 days prior to the collection of the Cmin sample. Steady-state for the 5 mg every other day regimen was defined as the state when the 5 mg dose was taken 2 days and 4 days before sampling. PK samples were only drawn at visit 3, and only analyzed for patients receiving everolimus at steady state (if patients had received the dose the previous 4 days). In addition summary statistics were only done for each everolimus dose when 3 samples were available. Only valid pre-dose (Cmin) everolimus samples were included in the analysis.

Outcome measures

Measure	Everolimus + Best Supportive Care (BSC) n=206 Participants Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care n=10 Participants Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Pharmacokinetics Assessments - Cmin	16.141 ng/mL Standard Deviation 9.2297	9.318 ng/mL Standard Deviation 4.9705

SECONDARY outcome

Timeframe: Until all patients have disease progression or leave study due to intolerable adverse events- Estimate of 1 year for each patient.

Population: Safety Set consists of all patients who received at least one dose of study treatment with a valid postbaseline assessment. All PK analyses were based on the Safety Set.

Cmax is the maximum (peak) blood drug concentration after dose administration (ng/mL) calculated as the maximum of C1h and C2h. C1h was 1 hour post-dose blood concentration (ng/mL) and C2h was 2 hour post-dose blood concentration (ng/mL). C1h and C2h post-dose samples were collected from all patients in both arms at Visit 3. Steady-state for the C1h and C2h samples was defined as continuous administration of the same dose in the previous 4 days and the day on which the C1h and C2h samples were collected. Steady-state for the 5 mg every other day regimen was defined as the state when the 5 mg dose was taken 2 days and 4 days before sampling. PK samples were only drawn at visit 3, and only analyzed for patients receiving everolimus at steady state (if patients had received the dose the previous 4 days). In addition summary statistics were only done for each everolimus dose when 3 samples were available. Only valid C1h and C2h everolimus samples were included in the analysis.

Outcome measures

Measure	Everolimus + Best Supportive Care (BSC) n=229 Participants Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care n=13 Participants Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Pharmacokinetics Assessments - Cmax	47.881 ng/mL Standard Deviation 21.0999	31.592 ng/mL Standard Deviation 21.1622

Adverse Events

Everolimus + Best Supportive Care (BSC)

Serious events: 171 serious events

Other events: 343 other events

Deaths: 0 deaths

Placebo + Best Supportive Care

Serious events: 64 serious events

Other events: 147 other events

Deaths: 0 deaths

Serious adverse events

Measure	Everolimus + Best Supportive Care (BSC) n=361 participants at risk Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care n=182 participants at risk Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Blood and lymphatic system disorders Anaemia	3.9% 14/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.6% 3/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Blood and lymphatic system disorders Leukopenia	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Blood and lymphatic system disorders Neutropenia	0.83% 3/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Blood and lymphatic system disorders Thrombocytopenia	1.1% 4/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Angina pectoris	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Angina unstable	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Atrial fibrillation	1.1% 4/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Cardiac arrest	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Cardiac failure	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Cardiac failure congestive	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Cardio-respiratory arrest	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Ischaemic cardiomyopathy	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Mitral valve incompetence	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Myocardial ischaemia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Cardiac disorders Pericardial effusion	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Congenital, familial and genetic disorders Pyloric stenosis	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Eye disorders Cataract	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Eye disorders Ocular icterus	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Eye disorders Retinal detachment	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Abdominal distension	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Abdominal pain	2.5% 9/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	4.4% 8/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Abdominal pain upper	1.1% 4/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Ascites	3.6% 13/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	6.0% 11/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Colitis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Colitis ischaemic	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Colonic obstruction	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Constipation	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Dysphagia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Enteritis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Faeces discoloured	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Gastric antral vascular ectasia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Gastric haemorrhage	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Gastric ulcer	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.4% 5/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Haematemesis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Ileal ulcer	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Intestinal obstruction	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Intra-abdominal haemorrhage	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Large intestine perforation	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Melaena	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Mouth ulceration	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Oesophageal haemorrhage	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.6% 3/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Peritoneal haemorrhage	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Small intestinal haemorrhage	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Stomatitis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Subileus	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.83% 3/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Varices oesophageal	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Vomiting	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.6% 3/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Asthenia	2.5% 9/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.6% 3/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Chills	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Death	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Face oedema	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Fatigue	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders General physical health deterioration	1.4% 5/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	2.2% 4/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Hyperpyrexia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Malaise	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Multi-organ failure	0.83% 3/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Non-cardiac chest pain	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Oedema peripheral	1.1% 4/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Performance status decreased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Pyrexia	3.9% 14/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Sudden death	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Bile duct stenosis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Cholangitis	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Cholecystitis	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Cirrhosis alcoholic	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Hepatic cirrhosis	2.2% 8/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.6% 3/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Hepatic failure	1.4% 5/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	2.2% 4/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Hepatic pain	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Hepatorenal syndrome	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Hyperbilirubinaemia	1.4% 5/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	2.7% 5/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Jaundice	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Hepatobiliary disorders Jaundice cholestatic	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Immune system disorders Allergic oedema	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Atypical pneumonia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Bacteraemia	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Bacterial toxaemia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Bronchitis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Bronchopneumonia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Candidiasis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Cellulitis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Cholangitis suppurative	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Citrobacter infection	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Dengue fever	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Erysipelas	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Escherichia sepsis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Gastroenteritis	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Gastroenteritis bacterial	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Infection	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Listeriosis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Lung infection	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Morganella infection	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Peritonitis	1.1% 4/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Pneumocystis jiroveci pneumonia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Pneumonia	5.0% 18/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Sepsis	1.7% 6/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Septic shock	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Urinary tract infection	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Injury, poisoning and procedural complications Facial bones fracture	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Injury, poisoning and procedural complications Fall	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Injury, poisoning and procedural complications Hand fracture	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Injury, poisoning and procedural complications Overdose	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Injury, poisoning and procedural complications Radius fracture	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Aspartate aminotransferase increased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Blood bilirubin increased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Blood creatinine increased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Blood uric acid increased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations C-reactive protein abnormal	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Cardiac enzymes increased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations General physical condition abnormal	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Haemoglobin decreased	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations International normalised ratio increased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Platelet count decreased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Troponin increased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Weight decreased	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations White blood cell count decreased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations White blood cell count increased	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Cachexia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Decreased appetite	2.2% 8/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Dehydration	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Diabetes mellitus	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Failure to thrive	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Hyperammonaemia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Hypercalcaemia	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Hypercholesterolaemia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Hyperkalaemia	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.6% 3/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Hypoglycaemia	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Hypokalaemia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Hyponatraemia	1.7% 6/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Malnutrition	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Musculoskeletal and connective tissue disorders Bone pain	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Musculoskeletal and connective tissue disorders Mobility decreased	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Musculoskeletal and connective tissue disorders Myalgia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Musculoskeletal and connective tissue disorders Neck pain	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to peritoneum	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Altered state of consciousness	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Amnesia	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Cerebellar haemorrhage	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Cerebral haemorrhage	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Cerebral infarction	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Cerebrovascular accident	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Cognitive disorder	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Dementia	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Depressed level of consciousness	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Diabetic hyperosmolar coma	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Dysarthria	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Encephalopathy	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Haemorrhage intracranial	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Haemorrhagic stroke	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Hemiplegia	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Hepatic encephalopathy	1.4% 5/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Metabolic encephalopathy	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Nervous system disorder	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Sciatica	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Syncope	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Psychiatric disorders Anxiety	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Psychiatric disorders Confusional state	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.6% 3/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Psychiatric disorders Disorientation	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Psychiatric disorders Mental status changes	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Renal and urinary disorders Anuria	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Renal and urinary disorders Haematuria	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Renal and urinary disorders Renal disorder	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Renal and urinary disorders Renal failure	3.0% 11/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Renal and urinary disorders Renal failure acute	2.2% 8/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Renal and urinary disorders Renal failure chronic	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Reproductive system and breast disorders Testicular swelling	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Asthma	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Bronchial haemorrhage	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Bronchostenosis	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.5% 9/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	2.2% 4/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.5% 9/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	1.4% 5/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.83% 3/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.4% 5/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.55% 2/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.83% 3/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Skin and subcutaneous tissue disorders Angioedema	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Skin and subcutaneous tissue disorders Pruritus	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Skin and subcutaneous tissue disorders Rash	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Skin and subcutaneous tissue disorders Skin ulcer	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Social circumstances Immobilisation prolonged	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Vascular disorders Deep vein thrombosis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Vascular disorders Haematoma	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Vascular disorders Post thrombotic syndrome	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Vascular disorders Shock haemorrhagic	0.00% 0/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Vascular disorders Vascular compression	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Vascular disorders Vena cava thrombosis	0.28% 1/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.

Other adverse events

Measure	Everolimus + Best Supportive Care (BSC) n=361 participants at risk Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.	Placebo + Best Supportive Care n=182 participants at risk Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.
Blood and lymphatic system disorders Anaemia	15.5% 56/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	7.1% 13/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Blood and lymphatic system disorders Thrombocytopenia	11.1% 40/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.1% 2/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Abdominal pain	15.0% 54/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	14.8% 27/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Abdominal pain upper	7.8% 28/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	9.3% 17/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Ascites	14.1% 51/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	12.6% 23/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Constipation	8.6% 31/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	12.6% 23/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Diarrhoea	26.0% 94/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	13.7% 25/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Dry mouth	6.4% 23/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	2.7% 5/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Nausea	16.6% 60/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	13.7% 25/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Stomatitis	39.3% 142/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	4.9% 9/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Gastrointestinal disorders Vomiting	15.2% 55/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	9.3% 17/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Asthenia	16.3% 59/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	17.0% 31/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Fatigue	24.9% 90/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	16.5% 30/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Oedema peripheral	27.7% 100/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	13.7% 25/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
General disorders Pyrexia	23.8% 86/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	7.1% 13/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Infections and infestations Hepatitis B	6.9% 25/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	4.4% 8/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Alanine aminotransferase increased	3.0% 11/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	6.0% 11/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Aspartate aminotransferase increased	6.4% 23/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	10.4% 19/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Gamma-glutamyltransferase increased	5.0% 18/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	6.6% 12/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Platelet count decreased	5.8% 21/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.00% 0/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Investigations Weight decreased	9.4% 34/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	4.4% 8/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Decreased appetite	31.6% 114/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	14.8% 27/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Hyperglycaemia	5.5% 20/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.6% 3/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Metabolism and nutrition disorders Hypokalaemia	5.3% 19/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	0.55% 1/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Musculoskeletal and connective tissue disorders Back pain	6.6% 24/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	7.1% 13/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	5.3% 19/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	4.9% 9/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Dysgeusia	8.6% 31/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	2.2% 4/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Nervous system disorders Headache	7.2% 26/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	4.9% 9/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Psychiatric disorders Insomnia	10.2% 37/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	8.2% 15/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Cough	21.9% 79/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	12.6% 23/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 45/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	11.5% 21/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	21.6% 78/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	2.7% 5/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.3% 19/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	1.6% 3/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Skin and subcutaneous tissue disorders Dry skin	6.6% 24/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	3.3% 6/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Skin and subcutaneous tissue disorders Pruritus	17.7% 64/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	15.9% 29/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.
Skin and subcutaneous tissue disorders Rash	21.1% 76/361 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.	8.8% 16/182 Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: trialandresults.registries@novartis.com

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 the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER