A Study of Avastin (Bevacizumab) in Combination With Stan... | NCT00643565

ID	Type	Description	Link
2007-005017-19	EudraCT Number

Label	Type	Description	Intervention Names
Bevacizumab + Chemotherapy	Experimental	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.	Drug: Standard chemotherapy Drug: bevacizumab [Avastin]
Chemotherapy	Active Comparator	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.	Drug: Standard chemotherapy

Name	Type	Description	Arm Group Labels	Other Names
Standard chemotherapy	Drug	As prescribed	Bevacizumab + Chemotherapy Chemotherapy

Measure	Description	Time Frame
Percentage of Participants Who Experienced Event-Free Survival (EFS) Events as Per Independent Review Committee (IRC) Assessment	EFS events included tumor progression (IRC assessed), no evidence of response after 3 cycles of induction (derived from IRC assessment), second primary cancer, or death due to any cause. Data for participants who had not experienced an event by the time of clinical cut-off were censored at the date of the last disease assessment prior to the clinical cut-off date. Data for participants who did not have any post-baseline disease assessments were censored at the time of randomization. Tumor progression was defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) as at least a 20% increase in the disease measurement, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions, or evidence of clinical progression and unequivocal progression of existing non-target lesions.	Screening up to approximately 6.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years)
EFS Duration as Per IRC Assessment	EFS was defined as the time between randomization and occurrence of EFS event. EFS events are described in Outcome Measure 1. Median EFS was estimated using Kaplan-Meier estimates and 95% confidence intervals (CI) for median was computed using the method of Brookmeyer and Crowley.	Screening up to approximately 6.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years)

Measure	Description	Time Frame
Percentage of Participants With Objective Response Prior to First Local Therapy Assessed by RECIST v1.0 Criteria	Objective response prior to first local therapy (surgery and/or radiotherapy) was defined as complete response (CR) or partial response (PR) determined on two consecutive occasions >/=4 weeks apart. Tumor response was assessed as per IRC using RECIST v1.0. CR was defined as disappearance of all target and non-target lesions. If immunocytology was available, no disease was to be detected by that methodology. PR was defined as at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study entry.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Hôpital Enfants Reine Fabiola		Brussels		1020	Belgium
Cliniques Universitaires St-Luc

PubMed Identifier	Type	Citation	Retractions
35709412	Derived	Schoot RA, Chisholm JC, Casanova M, Minard-Colin V, Geoerger B, Cameron AL, Coppadoro B, Zanetti I, Orbach D, Kelsey A, Rogers T, Guizani C, Elze M, Ben-Arush M, McHugh K, van Rijn RR, Ferman S, Gallego S, Ferrari A, Jenney M, Bisogno G, Merks JHM. Metastatic Rhabdomyosarcoma: Results of the European Paediatric Soft Tissue Sarcoma Study Group MTS 2008 Study and Pooled Analysis With the Concurrent BERNIE Study. J Clin Oncol. 2022 Nov 10;40(32):3730-3740. doi: 10.1200/JCO.21.02981. Epub 2022 Jun 16.
32179448

ID	Title	Description
FG000	Chemotherapy	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Who Experienced Event-Free Survival (EFS) Events as Per Independent Review Committee (IRC) Assessment

EFS events included tumor progression (IRC assessed), no evidence of response after 3 cycles of induction (derived from IRC assessment), second primary cancer, or death due to any cause. Data for participants who had not experienced an event by the time of clinical cut-off were censored at the date of the last disease assessment prior to the clinical cut-off date. Data for participants who did not have any post-baseline disease assessments were censored at the time of randomization. Tumor progression was defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) as at least a 20% increase in the disease measurement, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions, or evidence of clinical progression and unequivocal progression of existing non-target lesions.

ITT population.

Posted

Number

percentage of participants

Screening up to approximately 6.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years)

ID	Title	Description
OG000	Chemotherapy	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.
OG001	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.

Units	Counts
Participants	OG00080 OG00174

Title

Denominators

Categories

Title	Measurements
	OG00052.5 OG00168.9

Secondary

Percentage of Participants With Objective Response Prior to First Local Therapy Assessed by RECIST v1.0 Criteria

Objective response prior to first local therapy (surgery and/or radiotherapy) was defined as complete response (CR) or partial response (PR) determined on two consecutive occasions >/=4 weeks apart. Tumor response was assessed as per IRC using RECIST v1.0. CR was defined as disappearance of all target and non-target lesions. If immunocytology was available, no disease was to be detected by that methodology. PR was defined as at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study entry.

ITT population.

Posted

Number

95% Confidence Interval

percentage of participants

Screening up to approximately 6.75 years

ID	Title	Description
OG000	Chemotherapy	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.
OG001	Bevacizumab + Chemotherapy

Secondary

Percentage of Participants Who Experienced EFS Events Among Participants Who Had Objective Response

EFS events was described in Outcome Measure 1 and Outcome Measure 3.

ITT population. Here number of participants analyzed = participants available for the analysis of this outcome measure.

Posted

Number

percentage of participants

Screening up to approximately 6.75 years

ID	Title	Description
OG000	Chemotherapy	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.
OG001	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.

Secondary

Duration of Response

Duration of Response was defined as time between first objective response and the occurrence of an EFS event (described in Outcome Measure 1). Objective response was defined in Outcome Measure 3. Median duration of response was estimated using Kaplan-Meier estimates and 95% CI for median was computed using the method of Brookmeyer and Crowley.

ITT population. Here, number of participants analyzed = participants who were evaluable for this outcome measure.

Posted

Median

95% Confidence Interval

months

Screening up to approximately 6.75 years

ID	Title	Description
OG000	Chemotherapy	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.
OG001	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.

Secondary

Percentage of Participants Who Died

ITT population.

Posted

Number

percentage of participants

Screening up to approximately 10.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years.

ID	Title	Description
OG000	Chemotherapy	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.
OG001	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.

Primary

EFS Duration as Per IRC Assessment

EFS was defined as the time between randomization and occurrence of EFS event. EFS events are described in Outcome Measure 1. Median EFS was estimated using Kaplan-Meier estimates and 95% confidence intervals (CI) for median was computed using the method of Brookmeyer and Crowley.

ITT population.

Posted

Median

95% Confidence Interval

months

ID	Title	Description
OG000	Chemotherapy	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.
OG001	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.

Secondary

Overall Survival Duration

Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Median overall survival was estimated using Kaplan-Meier estimates and 95% CI for median was computed using the method of Brookmeyer and Crowley.

ITT population. Here number of participants analyzed = participants available for the analysis of this outcome measure.

Posted

Median

95% Confidence Interval

months

ID	Title	Description
OG000	Chemotherapy	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.
OG001	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.

Secondary

Area Under the Curve at Steady State (AUCss) of Bevacizumab

AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUCss is expressed in milligrams times days per milliliter (mg*day/mL).

Pharmacokinetic (PK)-evaluable population included all randomized participants for whom at least one blood sample was taken for PK assessment following bevacizumab administration. Here, number of participants analyzed = participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

mg*day/mL

Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase

ID	Title	Description
OG000	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.

Secondary

Volume of Distribution of Bevacizumab

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

PK-evaluable population. Only participants who received bevacizumab were to be analyzed for PK assessment.

Posted

Mean

Standard Deviation

Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase (1 cycle = 3 weeks)

ID	Title	Description
OG000	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.

Secondary

Half-Life of Bevacizumab

Half-life is the time measured for the plasma concentration to decrease by one half.

PK-evaluable population. Only participants who received bevacizumab were to be analyzed for PK assessment.

Posted

Mean

Standard Deviation

days

Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase (1 cycle = 3 weeks)

ID	Title	Description
OG000	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.

Units	Counts
Participants

Secondary

Clearance of Bevacizumab

CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL is expressed in milliliters per day (mL/day).

PK-evaluable population. Only participants who received bevacizumab were to be analyzed for PK assessment.

Posted

Mean

Standard Deviation

mL/day

Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase (1 cycle = 3 weeks)

ID	Title	Description
OG000	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0008 events3 affected79 at risk EG0017 events4 affected71 at risk
Febrile bone marrow aplasia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG00024 events9 affected79 at risk EG00149 events19 affected71 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG000135 events47 affected79 at risk EG001120 events46 affected71 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 events3 affected79 at risk EG0014 events2 affected71 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Atrial thrombosis	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Bradycardia	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Cardiac failure	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Cardiotoxicity	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Fanconi syndrome	Congenital, familial and genetic disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Eyelid oedema	Eye disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0012 events2 affected71 at risk
Anal fissure	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Anal inflammation	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Colitis	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Constipation	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0012 events2 affected71 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0003 events3 affected79 at risk EG0014 events4 affected71 at risk
Gastrointestinal inflammation	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected71 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Ileus	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Ileus paralytic	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0003 events3 affected79 at risk EG0011 events1 affected71 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0011 events1 affected71 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0005 events4 affected79 at risk EG0015 events3 affected71 at risk
Vomiting	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0008 events7 affected79 at risk EG00110 events8 affected71 at risk
Device related thrombosis	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Face oedema	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
General physical health deterioration	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0011 events1 affected71 at risk
Impaired healing	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Mucosal inflammation	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG00014 events7 affected79 at risk EG00118 events10 affected71 at risk
Performance status decreased	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Pyrexia	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG00026 events15 affected79 at risk EG00114 events14 affected71 at risk
Abdominal abscess	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Bacteriaemia	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0013 events2 affected71 at risk
Bacterial sepsis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Bronchitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0012 events2 affected71 at risk
Candida sepsis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Cellulitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Cystitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Device related infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected71 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Gastroenteritis bacterial	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Herpes zoster	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0013 events3 affected71 at risk
Infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0008 events5 affected79 at risk EG0016 events3 affected71 at risk
Localised infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Neutropenic infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0004 events3 affected79 at risk EG0017 events4 affected71 at risk
Oral candidiasis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Pneumonia	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Pseudomonas infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Pyelonephritis acute	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Salmonellosis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Sepsis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0004 events3 affected79 at risk EG0010 events0 affected71 at risk
Skin infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Soft tissue infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Staphylococcal infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Streptococcal bacteraemia	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0012 events2 affected71 at risk
Varicella	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0012 events2 affected71 at risk
Vulvitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Vascular procedure complication	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Procedural pneumothorax	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0011 events1 affected71 at risk
Recall phenomenon	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Torus fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Tracheostomy malfunction	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Vascular access complication	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Candida test positive	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Haemoglobin decreased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0003 events1 affected79 at risk EG0010 events0 affected71 at risk
Neutrophil toxic granulation present	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Weight decreased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0003 events3 affected79 at risk EG0015 events5 affected71 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0014 events4 affected71 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected71 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected71 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected71 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0012 events2 affected71 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0012 events2 affected71 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Tumour necrosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Encephalopathy	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0003 events2 affected79 at risk EG0010 events0 affected71 at risk
Facial nerve disorder	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Neuralgia	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0012 events2 affected71 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Neurotoxicity	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Peripheral sensorimotor neuropathy	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Presyncope	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Seizure	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0014 events4 affected71 at risk
Spinal cord compression	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Toxic encephalopathy	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected71 at risk
Vocal cord paresis	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected71 at risk
Bladder necrosis	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Dysuria	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Haematuria	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0005 events4 affected79 at risk EG0010 events0 affected71 at risk
Proteinuria	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Renal impairment	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Urinary retention	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected71 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0005 events1 affected79 at risk EG0011 events1 affected71 at risk
Hypoventilation	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0011 events1 affected71 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0012 events2 affected71 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Central venous catheter removal	Surgical and medical procedures	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Hypotension	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 events2 affected79 at risk EG0010 events0 affected71 at risk
Jugular vein thrombosis	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Microangiopathy	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk
Venoocclusive disease	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Vascular device infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Device Malfunction	Product Issues	MedDRA (22.0)	Non-systematic Assessment	EG0001 events1 affected79 at risk EG0010 events0 affected71 at risk
Device Dislocation	Product Issues	MedDRA (22.0)	Non-systematic Assessment	EG0000 events0 affected79 at risk EG0011 events1 affected71 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG00050 affected79 at risk EG00155 affected71 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG00014 affected79 at risk EG00112 affected71 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG00011 affected79 at risk EG00113 affected71 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG00053 affected79 at risk EG00156 affected71 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (22.0)	Non-systematic Assessment	EG00037 affected79 at risk EG00131 affected71 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0015 affected71 at risk
Tachycardia	Cardiac disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0011 affected71 at risk
Ear pain	Ear and labyrinth disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0015 affected71 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG00027 affected79 at risk EG00131 affected71 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0008 affected79 at risk EG0018 affected71 at risk
Anal fissure	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0005 affected79 at risk EG00113 affected71 at risk
Anal inflammation	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0016 affected71 at risk
Constipation	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG00040 affected79 at risk EG00148 affected71 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG00027 affected79 at risk EG00130 affected71 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0005 affected79 at risk EG0014 affected71 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0013 affected71 at risk
Nausea	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG00042 affected79 at risk EG00144 affected71 at risk
Oral pain	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0012 affected71 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG00023 affected79 at risk EG00115 affected71 at risk
Vomiting	Gastrointestinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG00061 affected79 at risk EG00164 affected71 at risk
Asthenia	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG00010 affected79 at risk EG00117 affected71 at risk
Chest pain	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG0006 affected79 at risk EG0014 affected71 at risk
Fatigue	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG00016 affected79 at risk EG00118 affected71 at risk
Mucosal inflammation	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG00038 affected79 at risk EG00142 affected71 at risk
Pain	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG00010 affected79 at risk EG0015 affected71 at risk
Pyrexia	General disorders	MedDRA (22.0)	Non-systematic Assessment	EG00033 affected79 at risk EG00127 affected71 at risk
Hepatocellular injury	Hepatobiliary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected79 at risk EG0014 affected71 at risk
Hypersensitivity	Immune system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected79 at risk EG0014 affected71 at risk
Candida infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0005 affected79 at risk EG0010 affected71 at risk
Conjunctivitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0005 affected79 at risk EG0017 affected71 at risk
Ear infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0003 affected79 at risk EG0016 affected71 at risk
Herpes zoster	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0013 affected71 at risk
Infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0003 affected79 at risk EG0015 affected71 at risk
Nasopharyngitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0005 affected79 at risk EG00110 affected71 at risk
Oral candidiasis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0007 affected79 at risk EG0015 affected71 at risk
Paronychia	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected79 at risk EG0015 affected71 at risk
Pharyngitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0000 affected79 at risk EG0014 affected71 at risk
Rhinitis	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0006 affected79 at risk EG00112 affected71 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0007 affected79 at risk EG0019 affected71 at risk
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected79 at risk EG0018 affected71 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected79 at risk EG0017 affected71 at risk
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG00012 affected79 at risk EG0018 affected71 at risk
Alanine aminotransferase increased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected79 at risk EG0016 affected71 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0003 affected79 at risk EG0014 affected71 at risk
Haemoglobin decreased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG00013 affected79 at risk EG0017 affected71 at risk
Neutrophil count decreased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0013 affected71 at risk
Platelet count decreased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0005 affected79 at risk EG0014 affected71 at risk
Weight decreased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG00027 affected79 at risk EG00122 affected71 at risk
White blood cell count decreased	Investigations	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected79 at risk EG0014 affected71 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG00018 affected79 at risk EG00121 affected71 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG00018 affected79 at risk EG0018 affected71 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0005 affected79 at risk EG0012 affected71 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected79 at risk EG0014 affected71 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0015 affected71 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0008 affected79 at risk EG00110 affected71 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0006 affected79 at risk EG00115 affected71 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected79 at risk EG0014 affected71 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0016 affected71 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG00016 affected79 at risk EG00120 affected71 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG00012 affected79 at risk EG0015 affected71 at risk
Dizziness	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0006 affected79 at risk EG0017 affected71 at risk
Headache	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG00016 affected79 at risk EG00132 affected71 at risk
Neuralgia	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0005 affected79 at risk EG0012 affected71 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected79 at risk EG0019 affected71 at risk
Paraesthesia	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0003 affected79 at risk EG0016 affected71 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected79 at risk EG0015 affected71 at risk
Polyneuropathy	Nervous system disorders	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected79 at risk EG0014 affected71 at risk
Anxiety	Psychiatric disorders	MedDRA (22.0)	Non-systematic Assessment	EG0007 affected79 at risk EG0019 affected71 at risk
Insomnia	Psychiatric disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected79 at risk EG0015 affected71 at risk
Dysuria	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0003 affected79 at risk EG0017 affected71 at risk
Haematuria	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected79 at risk EG0018 affected71 at risk
Proteinuria	Renal and urinary disorders	MedDRA (22.0)	Non-systematic Assessment	EG0004 affected79 at risk EG0014 affected71 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG00013 affected79 at risk EG00119 affected71 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0008 affected79 at risk EG00123 affected71 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0007 affected79 at risk EG0019 affected71 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Non-systematic Assessment	EG0006 affected79 at risk EG0014 affected71 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG00022 affected79 at risk EG00117 affected71 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0002 affected79 at risk EG0015 affected71 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0006 affected79 at risk EG00112 affected71 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG0006 affected79 at risk EG00110 affected71 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Non-systematic Assessment	EG00010 affected79 at risk EG0015 affected71 at risk
Hypotension	Vascular disorders	MedDRA (22.0)	Non-systematic Assessment	EG0003 affected79 at risk EG0014 affected71 at risk
Radiation Injury	Injury, poisoning and procedural complications	MedDRA (22.0)	Non-systematic Assessment	EG0001 affected79 at risk EG0014 affected71 at risk

ID	Term
D018204	Neoplasms, Connective and Soft Tissue
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	Chemotherapy	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.
BG001	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Chemotherapy	Participants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.	40	79	68	79	78	79
EG001	Bevacizumab + Chemotherapy	Participants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.	37	71	66	71	71	71