Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) in Combination With Standard Chemotherapy in Children and Adolescents With Sarcoma. (NCT NCT00643565)

NCT ID: NCT00643565

Last Updated: 2019-10-22

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 154 participants
• Primary outcome timeframe: 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)
• Results posted on: 2019-10-22

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	80	74
Overall Study COMPLETED	7	7
Overall Study NOT COMPLETED	73	67

Reasons for withdrawal

Measure	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.	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.
Overall Study Death	12	11
Overall Study Withdrawal by Subject	4	1
Overall Study Lost to Follow-up	0	6
Overall Study Other	7	8
Overall Study Refused Treatment / Did Not Cooperate	0	1
Overall Study Recurrence of Disease	2	1
Overall Study Progression of Disease	18	14
Overall Study Protocol Violation	3	0
Overall Study Did Not Cooperate	0	1
Overall Study Administrative	22	16
Overall Study Adverse Event	5	8

Baseline Characteristics

A Study of Avastin (Bevacizumab) in Combination With Standard Chemotherapy in Children and Adolescents With Sarcoma.

Baseline characteristics by cohort

Measure	Chemotherapy n=80 Participants 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.	Bevacizumab + Chemotherapy n=74 Participants 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.	Total n=154 Participants Total of all reporting groups
Age, Continuous	10.5 years STANDARD_DEVIATION 4.8 • n=5 Participants	10.3 years STANDARD_DEVIATION 4.9 • n=7 Participants	10.4 years STANDARD_DEVIATION 4.9 • n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	29 Participants n=7 Participants	69 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	45 Participants n=7 Participants	85 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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)

Population: ITT population.

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.

Outcome measures

Measure	Chemotherapy n=80 Participants 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.	Bevacizumab + Chemotherapy n=74 Participants 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.
Percentage of Participants Who Experienced Event-Free Survival (EFS) Events as Per Independent Review Committee (IRC) Assessment	52.5 percentage of participants	68.9 percentage of participants

PRIMARY outcome

Timeframe: 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)

Population: ITT population.

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.

Outcome measures

Measure	Chemotherapy n=80 Participants 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.	Bevacizumab + Chemotherapy n=74 Participants 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.
EFS Duration as Per IRC Assessment	14.85 months Interval 10.84 to 35.88	20.63 months Interval 15.15 to 24.87

SECONDARY outcome

Timeframe: Screening up to approximately 6.75 years

Population: ITT population.

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.

Outcome measures

Measure	Chemotherapy n=80 Participants 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.	Bevacizumab + Chemotherapy n=74 Participants 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.
Percentage of Participants With Objective Response Prior to First Local Therapy Assessed by RECIST v1.0 Criteria	36.0 percentage of participants Interval 25.23 to 47.91	54.0 percentage of participants Interval 40.94 to 66.61

SECONDARY outcome

Timeframe: Screening up to approximately 6.75 years

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

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

Outcome measures

Measure	Chemotherapy n=27 Participants 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.	Bevacizumab + Chemotherapy n=34 Participants 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.
Percentage of Participants Who Experienced EFS Events Among Participants Who Had Objective Response	40.7 percentage of participants	76.5 percentage of participants

SECONDARY outcome

Timeframe: Screening up to approximately 6.75 years

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

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.

Outcome measures

Measure	Chemotherapy n=27 Participants 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.	Bevacizumab + Chemotherapy n=34 Participants 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.
Duration of Response	NA months Interval 10.18 to Data was not estimable because of higher number (more than 50%) of censored participants in this arm group.	17.48 months Interval 12.29 to 25.23

SECONDARY outcome

Timeframe: 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.

Population: ITT population.

Outcome measures

Measure	Chemotherapy n=80 Participants 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.	Bevacizumab + Chemotherapy n=74 Participants 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.
Percentage of Participants Who Died	50 percentage of participants	51.4 percentage of participants

SECONDARY outcome

Timeframe: 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)

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

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.

Outcome measures

Measure	Chemotherapy n=80 Participants 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.	Bevacizumab + Chemotherapy n=74 Participants 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.
Overall Survival Duration	24.02 months Interval 17.97 to Upper limit of 95% CI was not estimable because of the high number (approximately 50%) of censored participants in this arm group	32.79 months Interval 25.33 to Upper limit of 95% CI was not estimable because of the high number (approximately 50%) of censored participants in this arm group

SECONDARY outcome

Timeframe: 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

Population: 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.

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).

Outcome measures

Measure	Chemotherapy n=70 Participants 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.	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.
Area Under the Curve at Steady State (AUCss) of Bevacizumab	1010 mg*day/mL Standard Deviation 256	—

SECONDARY outcome

Timeframe: 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)

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

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.

Outcome measures

Measure	Chemotherapy n=70 Participants 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.	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.
Volume of Distribution of Bevacizumab	2070 mL Standard Deviation 891	—

SECONDARY outcome

Timeframe: 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)

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

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

Outcome measures

Measure	Chemotherapy n=70 Participants 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.	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.
Half-Life of Bevacizumab	20.8 days Standard Deviation 8.58	—

SECONDARY outcome

Timeframe: 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)

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

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).

Outcome measures

Measure	Chemotherapy n=70 Participants 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.	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.
Clearance of Bevacizumab	167 mL/day Standard Deviation 76.4	—

Adverse Events

Chemotherapy

Serious events: 68 serious events

Other events: 78 other events

Deaths: 40 deaths

Bevacizumab + Chemotherapy

Serious events: 66 serious events

Other events: 71 other events

Deaths: 37 deaths

Serious adverse events

Measure	Chemotherapy n=79 participants at risk 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.	Bevacizumab + Chemotherapy n=71 participants at risk 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.
Metabolism and nutrition disorders Metabolic acidosis	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour necrosis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Cerebral haemorrhage	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Encephalopathy	2.5% 2/79 • Number of events 3 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Facial nerve disorder	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Neuralgia	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Neuropathy peripheral	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Neurotoxicity	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Peripheral sensorimotor neuropathy	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Presyncope	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Seizure	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Number of events 4 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Spinal cord compression	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Toxic encephalopathy	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Vocal cord paresis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Renal and urinary disorders Acute kidney injury	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Renal and urinary disorders Bladder necrosis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Renal and urinary disorders Dysuria	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Renal and urinary disorders Haematuria	5.1% 4/79 • Number of events 5 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Renal and urinary disorders Proteinuria	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Renal and urinary disorders Renal impairment	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Renal and urinary disorders Urinary retention	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.3% 1/79 • Number of events 5 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Hypoventilation	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Skin and subcutaneous tissue disorders Rash papular	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Skin and subcutaneous tissue disorders Skin disorder	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Surgical and medical procedures Central venous catheter removal	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Vascular disorders Hypotension	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Vascular disorders Jugular vein thrombosis	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Vascular disorders Microangiopathy	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Vascular disorders Venoocclusive disease	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Vascular device infection	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Product Issues Device Malfunction	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Product Issues Device Dislocation	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Blood and lymphatic system disorders Anaemia	3.8% 3/79 • Number of events 8 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Number of events 7 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Blood and lymphatic system disorders Febrile bone marrow aplasia	11.4% 9/79 • Number of events 24 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	26.8% 19/71 • Number of events 49 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Blood and lymphatic system disorders Febrile neutropenia	59.5% 47/79 • Number of events 135 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	64.8% 46/71 • Number of events 120 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Blood and lymphatic system disorders Neutropenia	3.8% 3/79 • Number of events 4 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 4 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Blood and lymphatic system disorders Thrombocytopenia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Cardiac disorders Atrial thrombosis	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Cardiac disorders Bradycardia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Cardiac disorders Cardiac failure	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Cardiac disorders Cardiotoxicity	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Cardiac disorders Left ventricular dysfunction	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Cardiac disorders Ventricular arrhythmia	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Congenital, familial and genetic disorders Fanconi syndrome	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Eye disorders Eyelid oedema	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Abdominal pain	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Anal fissure	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Anal inflammation	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Colitis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Constipation	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Diarrhoea	3.8% 3/79 • Number of events 3 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Number of events 4 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Gastrointestinal inflammation	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Gastrointestinal obstruction	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Ileus	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Ileus paralytic	3.8% 3/79 • Number of events 3 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Pancreatitis	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Pancreatitis acute	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Stomatitis	5.1% 4/79 • Number of events 5 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	4.2% 3/71 • Number of events 5 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Vomiting	8.9% 7/79 • Number of events 8 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	11.3% 8/71 • Number of events 10 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Device related thrombosis	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Face oedema	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders General physical health deterioration	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Impaired healing	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Mucosal inflammation	8.9% 7/79 • Number of events 14 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	14.1% 10/71 • Number of events 18 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Performance status decreased	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Pyrexia	19.0% 15/79 • Number of events 26 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	19.7% 14/71 • Number of events 14 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Abdominal abscess	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Bacteriaemia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 3 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Bacterial sepsis	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Bronchitis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Candida sepsis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Cellulitis	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Clostridium difficile colitis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Cystitis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Device related infection	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Escherichia bacteraemia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Gastroenteritis bacterial	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Herpes zoster	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	4.2% 3/71 • Number of events 3 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Infection	6.3% 5/79 • Number of events 8 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	4.2% 3/71 • Number of events 6 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Localised infection	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Neutropenic infection	3.8% 3/79 • Number of events 4 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Number of events 7 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Oral candidiasis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Pneumonia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Pseudomonas infection	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Pyelonephritis acute	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Salmonellosis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Sepsis	3.8% 3/79 • Number of events 4 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Skin infection	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Soft tissue infection	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Staphylococcal bacteraemia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Staphylococcal infection	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Streptococcal bacteraemia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Urinary tract infection	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Varicella	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Vulvitis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Lower limb fracture	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Vascular procedure complication	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Procedural pneumothorax	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Recall phenomenon	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Torus fracture	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Tracheostomy malfunction	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Vascular access complication	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations Candida test positive	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations Haemoglobin decreased	1.3% 1/79 • Number of events 3 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations Neutrophil toxic granulation present	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations Weight decreased	3.8% 3/79 • Number of events 3 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Number of events 5 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Decreased appetite	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Number of events 4 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Electrolyte imbalance	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Hypercalcaemia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Hypokalaemia	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Hyponatraemia	2.5% 2/79 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Hypophagia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Hypophosphataemia	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Malnutrition	1.3% 1/79 • Number of events 1 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Number of events 2 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.

Other adverse events

Measure	Chemotherapy n=79 participants at risk 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.	Bevacizumab + Chemotherapy n=71 participants at risk 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.
Blood and lymphatic system disorders Anaemia	63.3% 50/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	77.5% 55/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Blood and lymphatic system disorders Febrile neutropenia	17.7% 14/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	16.9% 12/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Blood and lymphatic system disorders Leukopenia	13.9% 11/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	18.3% 13/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Blood and lymphatic system disorders Neutropenia	67.1% 53/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	78.9% 56/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Blood and lymphatic system disorders Thrombocytopenia	46.8% 37/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	43.7% 31/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Cardiac disorders Left ventricular dysfunction	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Cardiac disorders Tachycardia	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	1.4% 1/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Ear and labyrinth disorders Ear pain	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Abdominal pain	34.2% 27/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	43.7% 31/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Abdominal pain upper	10.1% 8/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	11.3% 8/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Anal fissure	6.3% 5/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	18.3% 13/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Anal inflammation	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	8.5% 6/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Constipation	50.6% 40/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	67.6% 48/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Diarrhoea	34.2% 27/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	42.3% 30/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Dyspepsia	6.3% 5/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Mouth ulceration	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	4.2% 3/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Nausea	53.2% 42/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	62.0% 44/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Oral pain	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Stomatitis	29.1% 23/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	21.1% 15/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Gastrointestinal disorders Vomiting	77.2% 61/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	90.1% 64/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Asthenia	12.7% 10/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	23.9% 17/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Chest pain	7.6% 6/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Fatigue	20.3% 16/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	25.4% 18/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Mucosal inflammation	48.1% 38/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	59.2% 42/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Pain	12.7% 10/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
General disorders Pyrexia	41.8% 33/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	38.0% 27/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Hepatobiliary disorders Hepatocellular injury	1.3% 1/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Immune system disorders Hypersensitivity	1.3% 1/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Candida infection	6.3% 5/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	0.00% 0/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Conjunctivitis	6.3% 5/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	9.9% 7/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Ear infection	3.8% 3/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	8.5% 6/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Herpes zoster	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	4.2% 3/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Infection	3.8% 3/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Nasopharyngitis	6.3% 5/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	14.1% 10/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Oral candidiasis	8.9% 7/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Paronychia	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Pharyngitis	0.00% 0/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Rhinitis	7.6% 6/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	16.9% 12/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Upper respiratory tract infection	8.9% 7/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	12.7% 9/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Infections and infestations Urinary tract infection	2.5% 2/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	11.3% 8/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Procedural pain	1.3% 1/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	9.9% 7/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Radiation skin injury	15.2% 12/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	11.3% 8/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations Alanine aminotransferase increased	2.5% 2/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	8.5% 6/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations Gamma-glutamyltransferase increased	3.8% 3/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations Haemoglobin decreased	16.5% 13/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	9.9% 7/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations Neutrophil count decreased	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	4.2% 3/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations Platelet count decreased	6.3% 5/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations Weight decreased	34.2% 27/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	31.0% 22/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Investigations White blood cell count decreased	2.5% 2/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Decreased appetite	22.8% 18/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	29.6% 21/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Hypokalaemia	22.8% 18/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	11.3% 8/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Hypomagnesaemia	6.3% 5/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Hyponatraemia	2.5% 2/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Metabolism and nutrition disorders Hypophosphataemia	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	10.1% 8/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	14.1% 10/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	7.6% 6/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	21.1% 15/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Musculoskeletal and connective tissue disorders Bone pain	2.5% 2/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Musculoskeletal and connective tissue disorders Myalgia	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	8.5% 6/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	20.3% 16/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	28.2% 20/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in jaw	15.2% 12/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Dizziness	7.6% 6/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	9.9% 7/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Headache	20.3% 16/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	45.1% 32/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Neuralgia	6.3% 5/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	2.8% 2/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Neuropathy peripheral	2.5% 2/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	12.7% 9/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Paraesthesia	3.8% 3/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	8.5% 6/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Peripheral sensory neuropathy	2.5% 2/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Nervous system disorders Polyneuropathy	1.3% 1/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Psychiatric disorders Anxiety	8.9% 7/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	12.7% 9/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Psychiatric disorders Insomnia	2.5% 2/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Renal and urinary disorders Dysuria	3.8% 3/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	9.9% 7/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Renal and urinary disorders Haematuria	2.5% 2/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	11.3% 8/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Renal and urinary disorders Proteinuria	5.1% 4/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	16.5% 13/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	26.8% 19/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.1% 8/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	32.4% 23/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.9% 7/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	12.7% 9/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	7.6% 6/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Skin and subcutaneous tissue disorders Alopecia	27.8% 22/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	23.9% 17/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Skin and subcutaneous tissue disorders Dry skin	2.5% 2/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Skin and subcutaneous tissue disorders Erythema	7.6% 6/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	16.9% 12/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	7.6% 6/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	14.1% 10/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Skin and subcutaneous tissue disorders Rash	12.7% 10/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	7.0% 5/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Vascular disorders Hypotension	3.8% 3/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.
Injury, poisoning and procedural complications Radiation Injury	1.3% 1/79 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.	5.6% 4/71 • Screening up to approximately 10.75 years. The safety-evaluable population included all randomized patients who received any dose of study treatment.

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER