Trial Outcomes & Findings for A Study of Bevacizumab (Avastin) in Combination With Capecitabine (Xeloda) in Elderly Patients With Metastatic Colorectal Cancer (NCT NCT00484939)

Last Updated: 2015-01-08

Results Overview

Progression-free survival was defined as the time in months from the date of randomization to the date of disease progression or death from any cause, whichever occurred first. All measurable lesions (maximum of 5 per organ and 10 in total, those with the longest diameter and suitability for accurate repeated measurements) were identified as target lesions (TL). A sum of the longest diameter for all TLs was calculated and reported as the baseline sum longest diameter (SLD). All other lesions were identified as non-TLs and recorded at baseline. PD was defined as ≥ 20% increase in the sum of the longest diameter of TLs, taking as reference the smallest SLD recorded since treatment started, the unequivocal progression of existing non-TLs, or the appearance of 1 or more new lesions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

280 participants

Primary outcome timeframe

Baseline to the end of the study (up to 5 years 8 months)

Results posted on

2015-01-08

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Overall Study STARTED	140	140
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	140	140

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Overall Study Death	9	13
Overall Study Adverse Event	22	12
Overall Study Patient Withdrew Consent	19	10
Overall Study Protocol Violation	3	3
Overall Study Lost to Follow-up	0	3
Overall Study Discretion of Investigator or Sponsor	7	3
Overall Study Disease progression	67	88
Overall Study Screen Failure	2	2
Overall Study Reason Not Specified	11	6

Baseline Characteristics

A Study of Bevacizumab (Avastin) in Combination With Capecitabine (Xeloda) in Elderly Patients With Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab + Capecitabine n=140 Participants Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=140 Participants Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Total n=280 Participants Total of all reporting groups
Age, Continuous	76.1 years STANDARD_DEVIATION 4.18 • n=5 Participants	76.5 years STANDARD_DEVIATION 3.91 • n=7 Participants	76.3 years STANDARD_DEVIATION 4.04 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	56 Participants n=7 Participants	112 Participants n=5 Participants
Sex: Female, Male Male	84 Participants n=5 Participants	84 Participants n=7 Participants	168 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to the end of the study (up to 5 years 8 months)

Population: Intent-to-treat population: All participants randomized into the study.

Outcome measures

Outcome measures
Measure	Bevacizumab + Capecitabine n=140 Participants Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=140 Participants Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Progression-free Survival	9.1 Months Interval 7.3 to 11.3	5.1 Months Interval 4.3 to 6.3

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 5 years 8 months)

Population: Intent-to-treat population: All participants randomized into the study. Only participants with a response were included in the analysis.

BOR was defined as the best response (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\], not evaluable \[NE\], or not assessed \[NA\]) recorded from the start of study treatment until disease progression (PD) or death. CR was defined as the disappearance of all target (TL) and non-target lesions (non-TL). PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD, or the persistence of 1 or more non-TLs. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since treatment started. For non-TLs, SD was defined as the persistence of 1 or more lesions. PD was defined as ≥ 20% increase in the sum of the longest diameter of TLs, taking as reference the smallest SLD recorded since treatment started, the unequivocal progression of existing non-TLs, or the appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Bevacizumab + Capecitabine n=140 Participants Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=140 Participants Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Best Overall Response (BOR) Complete Response	2.9 Percentage of participants Interval 0.8 to 7.2	1.4 Percentage of participants Interval 0.2 to 5.1
Best Overall Response (BOR) Partial Response	17.1 Percentage of participants Interval 11.3 to 24.4	8.6 Percentage of participants Interval 4.5 to 14.5
Best Overall Response (BOR) Stable Disease	54.3 Percentage of participants Interval 45.7 to 62.7	48.6 Percentage of participants Interval 40.0 to 57.2
Best Overall Response (BOR) Progressive Disease	10.0 Percentage of participants Interval 5.6 to 16.2	21.4 Percentage of participants Interval 14.9 to 29.2
Best Overall Response (BOR) Not assessed	15.7 Percentage of participants Interval 10.1 to 22.8	20.0 Percentage of participants Interval 13.7 to 27.6

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 5 years 8 months)

Population: Intent-to-treat population: All participants randomized into the study. Only participants with a complete response or partial response were included in the analysis.

Duration of response was defined as the time in months from the first confirmed complete response (CR) or partial response (PR) until disease progression or death from any cause, whichever occurred first. CR was defined as the disappearance of all target (TL) and non-target lesions (non-TL). PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD, or the persistence of 1 or more non-TLs.

Outcome measures

Outcome measures
Measure	Bevacizumab + Capecitabine n=28 Participants Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=14 Participants Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Duration of Response	9.7 Months Interval 8.3 to 10.9	9.4 Months Interval 6.2 to 12.6

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 5 years 8 months)

Population: Intent-to-treat population: All participants randomized into the study.

Time to response was defined as the time in months from the date of first study treatment to the date of the first documentation of complete response (CR) or partial response (PR), whichever occurred first. CR was defined as the disappearance of all target (TL) and non-target lesions (non-TL). PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD, or the persistence of 1 or more non-TLs. Participants who did not have a confirmed response were censored at the date of the last evaluable tumor assessment, or if that was unavailable, at the date of the first dose of study medication.

Outcome measures

Outcome measures
Measure	Bevacizumab + Capecitabine n=140 Participants Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=140 Participants Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Time to Response	NA Months The median and the lower and upper limits of the 95% confidence interval could not be calculated due to insufficient data.	NA Months Interval 30.4 to The median and the upper limit of the 95% confidence interval could not be calculated due to insufficient data.

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 5 years 8 months)

Population: Intent-to-treat population: All participants randomized into the study.

Overall survival was defined as the time in months from randomization to death from any cause.

Outcome measures

Outcome measures
Measure	Bevacizumab + Capecitabine n=140 Participants Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=140 Participants Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Overall Survival	20.7 Months Interval 16.6 to 26.0	17.0 Months Interval 12.9 to 22.0

SECONDARY outcome

Timeframe: Baseline to the Safety Follow-up which occurred 28 days after the last dose of treatment (up to 5 years 8 months).

Population: Intent-to-treat population: All participants randomized into the study.

The ECOG performance status is a scale used to quantify cancer patients' general well-being and activities of daily life. The scale ranges from 0 to 5, with 0 denoting perfect health and 5 indicating death. The 6 categories are 0=Asymptomatic (Fully active, able to carry on all predisease activities without restriction), 1=Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 2=Symptomatic, \< 50% in bed during the day (Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours), 3=Symptomatic, \> 50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours), 4=Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair), 5=Death. Reported is the percentage of participants in each of the 6 ECOG performance status categories.

Outcome measures

Outcome measures
Measure	Bevacizumab + Capecitabine n=140 Participants Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=140 Participants Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 7 ECOG = 0 (n=117,110)	50.4 Percentage of participants	34.5 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 7 ECOG = 1	47.0 Percentage of participants	58.2 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 7 ECOG = 2	1.7 Percentage of participants	5.5 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 7 ECOG = 3	0.9 Percentage of participants	1.8 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 7 ECOG = 4	0.0 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 7 ECOG = 5	0.0 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 16 ECOG = 0 (n=88,77)	50.0 Percentage of participants	36.4 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 16 ECOG = 1	45.5 Percentage of participants	51.9 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 16 ECOG = 2	3.4 Percentage of participants	11.7 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 16 ECOG = 3	1.1 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 16 ECOG = 4	0.0 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 16 ECOG = 5	0.0 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 25 ECOG = 0 (n=66,42)	43.9 Percentage of participants	45.2 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 25 ECOG = 1	48.5 Percentage of participants	45.2 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 34 ECOG = 2	0.0 Percentage of participants	8.3 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 25 ECOG = 2	6.1 Percentage of participants	9.5 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 25 ECOG = 3	1.5 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 25 ECOG = 4	0.0 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 25 ECOG = 5	0.0 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 34 ECOG = 0 (n=48,24)	39.6 Percentage of participants	33.3 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 34 ECOG = 1	58.3 Percentage of participants	58.3 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 34 ECOG = 3	2.1 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 34 ECOG = 4	0.0 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Week 34 ECOG = 5	0.0 Percentage of participants	0.0 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Safety Follow-up ECOG = 0 (n=89,82)	33.7 Percentage of participants	32.9 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Safety Follow-up ECOG = 1	47.2 Percentage of participants	45.1 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Safety Follow-up ECOG = 2	12.4 Percentage of participants	14.6 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Safety Follow-up ECOG = 3	6.7 Percentage of participants	4.9 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Safety Follow-up ECOG = 4	0.0 Percentage of participants	1.2 Percentage of participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Safety Follow-up ECOG = 5	0.0 Percentage of participants	1.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 5 years 8 months)

Population: Intent-to-treat population: All participants randomized into the study.

Reported is the percentage of participants requiring additional treatment for malignancy in the survival follow-up period.

Outcome measures

Outcome measures
Measure	Bevacizumab + Capecitabine n=140 Participants Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=140 Participants Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Percentage of Participants Requiring Additional Treatment for Malignancy	50.7 Percentage of participants	49.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to the end of the study (up to 5 years 8 months)

Population: Intent-to-treat population: All participants randomized into the study.

Duration of follow-up is defined as the time in days from randomization until disease progression or death, or time to censoring for overall survival.

Outcome measures

Outcome measures
Measure	Bevacizumab + Capecitabine n=140 Participants Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=140 Participants Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Duration of Follow-up	540.5 Days Standard Deviation 423.52	479.2 Days Standard Deviation 401.01

SECONDARY outcome

Timeframe: Throughout study

Outcome measures

Outcome data not reported

Adverse Events

Bevacizumab + Capecitabine

Serious events: 40 serious events

Other events: 129 other events

Deaths: 0 deaths

Capecitabine

Serious events: 42 serious events

Other events: 130 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

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

Measure	Bevacizumab + Capecitabine n=134 participants at risk Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=136 participants at risk Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Gastrointestinal disorders Abdominal pain	2.2% 3/134 Safety population: All participants who had at least 1 dose of study medication.	2.9% 4/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Intestinal obstruction	2.2% 3/134 Safety population: All participants who had at least 1 dose of study medication.	2.9% 4/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	1.5% 2/134 Safety population: All participants who had at least 1 dose of study medication.	1.5% 2/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Abdominal discomfort	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Haematochezia	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Inguinal hernia	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Nausea	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Small intestinal obstruction	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	2.9% 4/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Ascites	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	2.2% 3/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Colonic obstruction	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Mechanical ileus	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	6.0% 8/134 Safety population: All participants who had at least 1 dose of study medication.	1.5% 2/136 Safety population: All participants who had at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Pyrexia	2.2% 3/134 Safety population: All participants who had at least 1 dose of study medication.	1.5% 2/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders General physical health deterioration	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	1.5% 2/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Pain	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Death	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Oedema	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Asthenia	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Fatigue	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Infections and infestations Pneumonia	2.2% 3/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Infections and infestations Bronchitis	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Infections and infestations Escherichia urinary tract infection	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Infections and infestations Lower respiratory tract infection	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Infections and infestations Pneumonia bacterial	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Infections and infestations Pulmonary sepsis	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Infections and infestations Urosepsis	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Infections and infestations Cellulitis gangrenous	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Infections and infestations Gastroenteritis	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Infections and infestations Sepsis	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Nervous system disorders Transient ischaemic attack	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Nervous system disorders Amnesia	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Nervous system disorders Cerebral ischaemia	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Nervous system disorders Lethargy	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Nervous system disorders Somnolence	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Vascular disorders Hypertension	1.5% 2/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Vascular disorders Thrombosis	1.5% 2/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Vascular disorders Deep vein thrombosis	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	2.2% 3/136 Safety population: All participants who had at least 1 dose of study medication.
Vascular disorders Circulatory collapse	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Vascular disorders Peripheral artery thrombosis	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Vascular disorders Vena cava thrombosis	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Cardiac disorders Cardiac arrest	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	1.5% 2/136 Safety population: All participants who had at least 1 dose of study medication.
Cardiac disorders Angina pectoris	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Cardiac disorders Myocardial infarction	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Cardiac disorders Myocardial ischaemia	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Cardiac disorders Cardiac failure	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Injury, poisoning and procedural complications Excoriation	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Injury, poisoning and procedural complications Impacted fracture	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Injury, poisoning and procedural complications Patella fracture	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Injury, poisoning and procedural complications Spinal compression fracture	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Metabolism and nutrition disorders Dehydration	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	1.5% 2/136 Safety population: All participants who had at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Renal and urinary disorders Calculus ureteric	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Renal and urinary disorders Renal failure	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Groin pain	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Eye disorders Amaurosis fugax	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Reproductive system and breast disorders Female genital tract fistula	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Rash macular	0.75% 1/134 Safety population: All participants who had at least 1 dose of study medication.	0.00% 0/136 Safety population: All participants who had at least 1 dose of study medication.
Hepatobiliary disorders Jaundice	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	1.5% 2/136 Safety population: All participants who had at least 1 dose of study medication.
Hepatobiliary disorders Hepatic failure	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Hepatobiliary disorders Hepatitis acute	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Blood and lymphatic system disorders Anaemia	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Blood and lymphatic system disorders Neutropenia	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Surgical and medical procedures Bone operation	0.00% 0/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.

Measure	Bevacizumab + Capecitabine n=134 participants at risk Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.	Capecitabine n=136 participants at risk Participants received capecitabine 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Gastrointestinal disorders Diarrhoea	40.3% 54/134 Safety population: All participants who had at least 1 dose of study medication.	35.3% 48/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Nausea	23.9% 32/134 Safety population: All participants who had at least 1 dose of study medication.	27.2% 37/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain	23.1% 31/134 Safety population: All participants who had at least 1 dose of study medication.	15.4% 21/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	20.9% 28/134 Safety population: All participants who had at least 1 dose of study medication.	11.8% 16/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Constipation	18.7% 25/134 Safety population: All participants who had at least 1 dose of study medication.	14.0% 19/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Stomatitis	10.4% 14/134 Safety population: All participants who had at least 1 dose of study medication.	10.3% 14/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain upper	8.2% 11/134 Safety population: All participants who had at least 1 dose of study medication.	3.7% 5/136 Safety population: All participants who had at least 1 dose of study medication.
Gastrointestinal disorders Dyspepsia	6.7% 9/134 Safety population: All participants who had at least 1 dose of study medication.	2.9% 4/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Fatigue	23.9% 32/134 Safety population: All participants who had at least 1 dose of study medication.	27.2% 37/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Asthenia	22.4% 30/134 Safety population: All participants who had at least 1 dose of study medication.	16.2% 22/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Pyrexia	17.9% 24/134 Safety population: All participants who had at least 1 dose of study medication.	11.8% 16/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Mucosal inflammation	14.9% 20/134 Safety population: All participants who had at least 1 dose of study medication.	8.1% 11/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Oedema peripheral	8.2% 11/134 Safety population: All participants who had at least 1 dose of study medication.	12.5% 17/136 Safety population: All participants who had at least 1 dose of study medication.
General disorders Pain	8.2% 11/134 Safety population: All participants who had at least 1 dose of study medication.	4.4% 6/136 Safety population: All participants who had at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Palmar-Plantar erythrodysaesthesia syndrome	49.3% 66/134 Safety population: All participants who had at least 1 dose of study medication.	39.7% 54/136 Safety population: All participants who had at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	8.2% 11/134 Safety population: All participants who had at least 1 dose of study medication.	1.5% 2/136 Safety population: All participants who had at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Dry skin	6.0% 8/134 Safety population: All participants who had at least 1 dose of study medication.	2.9% 4/136 Safety population: All participants who had at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Rash	4.5% 6/134 Safety population: All participants who had at least 1 dose of study medication.	8.8% 12/136 Safety population: All participants who had at least 1 dose of study medication.
Nervous system disorders Lethargy	9.0% 12/134 Safety population: All participants who had at least 1 dose of study medication.	11.0% 15/136 Safety population: All participants who had at least 1 dose of study medication.
Nervous system disorders Headache	7.5% 10/134 Safety population: All participants who had at least 1 dose of study medication.	3.7% 5/136 Safety population: All participants who had at least 1 dose of study medication.
Nervous system disorders Dizziness	6.7% 9/134 Safety population: All participants who had at least 1 dose of study medication.	12.5% 17/136 Safety population: All participants who had at least 1 dose of study medication.
Nervous system disorders Dysgeusia	6.0% 8/134 Safety population: All participants who had at least 1 dose of study medication.	4.4% 6/136 Safety population: All participants who had at least 1 dose of study medication.
Nervous system disorders Paraesthesia	6.0% 8/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Epistaxis	17.2% 23/134 Safety population: All participants who had at least 1 dose of study medication.	3.7% 5/136 Safety population: All participants who had at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	11.2% 15/134 Safety population: All participants who had at least 1 dose of study medication.	8.8% 12/136 Safety population: All participants who had at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.0% 12/134 Safety population: All participants who had at least 1 dose of study medication.	9.6% 13/136 Safety population: All participants who had at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	6.7% 9/134 Safety population: All participants who had at least 1 dose of study medication.	1.5% 2/136 Safety population: All participants who had at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.0% 8/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Metabolism and nutrition disorders Decreased Appetite	28.4% 38/134 Safety population: All participants who had at least 1 dose of study medication.	22.8% 31/136 Safety population: All participants who had at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	9.7% 13/134 Safety population: All participants who had at least 1 dose of study medication.	8.1% 11/136 Safety population: All participants who had at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	9.0% 12/134 Safety population: All participants who had at least 1 dose of study medication.	2.9% 4/136 Safety population: All participants who had at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	8.2% 11/134 Safety population: All participants who had at least 1 dose of study medication.	3.7% 5/136 Safety population: All participants who had at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.5% 10/134 Safety population: All participants who had at least 1 dose of study medication.	2.9% 4/136 Safety population: All participants who had at least 1 dose of study medication.
Vascular disorders Hypertension	16.4% 22/134 Safety population: All participants who had at least 1 dose of study medication.	4.4% 6/136 Safety population: All participants who had at least 1 dose of study medication.
Psychiatric disorders Insomnia	5.2% 7/134 Safety population: All participants who had at least 1 dose of study medication.	5.1% 7/136 Safety population: All participants who had at least 1 dose of study medication.
Renal and urinary disorders Proteinuria	7.5% 10/134 Safety population: All participants who had at least 1 dose of study medication.	0.74% 1/136 Safety population: All participants who had at least 1 dose of study medication.
Blood and lymphatic system disorders Neutropenia	5.2% 7/134 Safety population: All participants who had at least 1 dose of study medication.	1.5% 2/136 Safety population: All participants who had at least 1 dose of study medication.