Combination Chemotherapy With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for High Risk Stage II or Stage III Colon Cancer

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ClinicalTrials.gov Identifier: NCT00112918

Recruitment Status : Completed

First Posted : June 3, 2005

Results First Posted : September 6, 2012

Last Update Posted : August 27, 2013

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Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Hoffmann-La Roche

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Colorectal Cancer
Interventions	Biological: Bevacizumab Drug: Capecitabine Drug: 5-Fluorouracil (5-FU) Drug: Leucovorin calcium Drug: Oxaliplatin
Enrollment	3451

Participant Flow

Recruitment Details
Pre-assignment Details	Randomization was stratified according to geographic region and disease stage (high-risk stage II or stage III N1 or stage III N2). The primary analysis population consisted of patients with Stage III disease.


Arm/Group Title	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
Arm/Group Description	Weeks 1-24: Oxaliplatin was adminis...	Weeks 1-24: Bevacizumab 5 mg/kg was...	Weeks 1-24: Bevacizumab 7.5 mg/kg w...
Arm/Group Description	Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-fluorouracil (5-FU), given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only.	Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).	Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).
Period Title: Overall Study
Started	1151	1155	1145
Received Treatment	1126	1145 ^[1]	1135
Stage III Disease Population	955	960	952
Completed	854 ^[2]	810 ^[2]	846 ^[2]
Not Completed	297	345	299
[1] Includes two patients from FOLFOX4 who received Bv and were assigned to FOLFOX4+Bv safety analysis [2] Represents patients alive in follow-up at the time of final data cut-off (30 June 2012)

Baseline Characteristics

Arm/Group Title		FOLFOX4	FOLFOX4 + Bv	XELOX+Bv	Total
Arm/Group Description		Weeks 1-24: Oxaliplatin was adminis...	Weeks 1-24: Bevacizumab 5 mg/kg was...	Weeks 1-24: Bevacizumab 7.5 mg/kg w...	Total of all reporting groups
Arm/Group Description		Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-fluorouracil (5-FU), given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only.	Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).	Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).	Total of all reporting groups
Overall Number of Baseline Participants		955	960	952	2867
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Baseline Measures are based on the Intent-to-Treat - Stage III Disease Patient Population.
Age, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	955 participants	960 participants	952 participants	2867 participants
<40		77	74	68	219
40-65		603	625	588	1816
>=65		275	261	296	832
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	955 participants	960 participants	952 participants	2867 participants
	Female	425 44.5%	473 49.3%	432 45.4%	1330 46.4%
	Male	530 55.5%	487 50.7%	520 54.6%	1537 53.6%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	955 participants	960 participants	952 participants	2867 participants
American Indian or Alaska Native		1	1	0	2
Asian		139	115	123	377
Black or African American		6	13	14	33
White		791	813	795	2399
Other		18	18	20	56

Outcome Measures

1.Primary Outcome


Title	Disease-free Survival in Stage III Cancer Patients - Time to Event
Description	Disease-free survival (DFS) was defined as the time from the date of r...
Description	Disease-free survival (DFS) was defined as the time from the date of randomization to the time of a recurrence, a new occurrence of colorectal cancer or death due to any cause, whichever occurred first. Patients without an event were censored at the last date the patient was known to be disease-free. Recurrence and new occurrence of colorectal cancer were based on tumor assessments made by the investigator. Patients with no tumor assessments after baseline but still alive at the time of the clinical cut-off were censored at day 1.
Time Frame	From first patient randomized until the data cut-off date of 30 June 2010 (36 months after the last patient randomized).

Outcome Measure Data

Analysis Population Description

The primary population for efficacy analyses was the intent to treat population (ITT; all randomized patients) with stage III disease.


Arm/Group Title	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
Arm/Group Description:	Weeks 1-24: Oxaliplatin was adminis...	Weeks 1-24: Bevacizumab 5 mg/kg was...	Weeks 1-24: Bevacizumab 7.5 mg/kg w...
Arm/Group Description:	Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only.	Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).	Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).
Overall Number of Participants Analyzed	955	960	952
Median (95% Confidence Interval) Unit of Measure: months
	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)

[1]

Median time to event and 95% confidence intervals could not be estimated due to the low number of events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FOLFOX4, FOLFOX4 + Bv, XELOX+Bv
	Comments	Adjustments for multiplicity was done using a closed test procedure which tests for differences between all three treatment groups at the 5% alpha level first. Only in case of a significant result, the pair-wise comparison between the control arm and each of the bevacizumab arm will be tested, again at the 5% alpha level.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2024
	Comments	[Not Specified]
	Method	Closed test procedure
	Comments	[Not Specified]

2.Primary Outcome


Title	Disease-free Survival in Stage III Cancer Patients - Number of Events
Description	A disease-free survival (DFS) event was composed of a recurrence, a ne...
Description	A disease-free survival (DFS) event was composed of a recurrence, a new occurrence of colorectal cancer or death due to any cause. Recurrence and new occurrence of colorectal cancer were based on tumor assessments made by the investigator. Triggering events for DFS are reported; a patient can have both recurrence and a new occurrence of colon cancer.
Time Frame	From first patient randomized until the data cut-off date of 30 June 2010 (36 months after the last patient randomized).

Outcome Measure Data

Analysis Population Description

The primary population for efficacy analyses was the intent to treat population (ITT; all randomized patients) with stage III disease.


Arm/Group Title	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
Arm/Group Description:	Weeks 1-24: Oxaliplatin was adminis...	Weeks 1-24: Bevacizumab 5 mg/kg was...	Weeks 1-24: Bevacizumab 7.5 mg/kg w...
Arm/Group Description:	Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only.	Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).	Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).
Overall Number of Participants Analyzed	955	960	952
Measure Type: Number Unit of Measure: participants
Patients with a DFS event	237	280	253
Recurrence	219	253	223
New Occurrence	3	8	6
Death	17	21	25
Patients without events	718	680	699

3.Secondary Outcome


Title	Overall Survival in Stage III Cancer Patients - Time to Event
Description	Overall survival was defined as the time between date of randomization...
Description	Overall survival was defined as the time between date of randomization and date of death due to any cause. Patients not reported as having died at the time of the analysis were censored at the date they were last known to be alive.
Time Frame	From first patient randomized until the clinical data cut-off date of 30 June 2010 (36 months after the last patient randomized).

Outcome Measure Data

Analysis Population Description

ITT patients with Stage III disease.


Arm/Group Title	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
Arm/Group Description:	Weeks 1-24: Oxaliplatin was adminis...	Weeks 1-24: Bevacizumab 5 mg/kg was...	Weeks 1-24: Bevacizumab 7.5 mg/kg w...
Arm/Group Description:	Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only.	Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).	Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).
Overall Number of Participants Analyzed	955	960	952
Median (95% Confidence Interval) Unit of Measure: months
	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)

[1]

Median time to event and 95% confidence intervals could not be estimated due to the low number of events.

4.Secondary Outcome


Title	Overall Survival in Stage III Cancer Patients - Number of Events
Description	An overall survival event was death due to any cause.
Description	An overall survival event was death due to any cause.
Time Frame	From first patient randomized until the clinical data cut-off date of 30 June 2010 (36 months after the last patient randomized).

Outcome Measure Data

Analysis Population Description

ITT patients with Stage III disease.


Arm/Group Title	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
Arm/Group Description:	Weeks 1-24: Oxaliplatin was adminis...	Weeks 1-24: Bevacizumab 5 mg/kg was...	Weeks 1-24: Bevacizumab 7.5 mg/kg w...
Arm/Group Description:	Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only.	Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).	Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).
Overall Number of Participants Analyzed	955	960	952
Measure Type: Number Unit of Measure: participants
Patients with events	115	151	145
Patients without events	840	809	807

5.Secondary Outcome


Title	Overall Survival in Stage III Cancer Patients - Time to Event: Final Analysis
Description	Overall survival was defined as the time between date of randomization...
Description	Overall survival was defined as the time between date of randomization and date of death due to any cause. Patients not reported as having died at the time of the clinical cut-off date (30 June 2012) were censored at the date they were last known to be alive.
Time Frame	From first patient randomized until the final data cut-off date of 30 June 2012 (5 years after the last patient randomized).

Outcome Measure Data

Analysis Population Description

ITT patients with Stage III disease.


Arm/Group Title	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
Arm/Group Description:	Weeks 1-24: Oxaliplatin was adminis...	Weeks 1-24: Bevacizumab 5 mg/kg was...	Weeks 1-24: Bevacizumab 7.5 mg/kg w...
Arm/Group Description:	Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only.	Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).	Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).
Overall Number of Participants Analyzed	955	960	952
Median (95% Confidence Interval) Unit of Measure: months
	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)

[1]

Median time to event and 95% confidence intervals could not be estimated due to the low number of events.

6.Secondary Outcome


Title	Overall Survival in Stage III Cancer Patients - Number of Events: Final Analysis
Description	An overall survival event was death due to any cause.
Description	An overall survival event was death due to any cause.
Time Frame	From first patient randomized until the final data cut-off date of 30 June 2012 (5 years after the last patient randomized).

Outcome Measure Data

Analysis Population Description

ITT patients with Stage III disease.


Arm/Group Title	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
Arm/Group Description:	Weeks 1-24: Oxaliplatin was adminis...	Weeks 1-24: Bevacizumab 5 mg/kg was...	Weeks 1-24: Bevacizumab 7.5 mg/kg w...
Arm/Group Description:	Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only.	Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).	Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).
Overall Number of Participants Analyzed	955	960	952
Measure Type: Number Unit of Measure: participants
Patients with events	161	202	182
Patients without events	794	758	770

Adverse Events

Time Frame	All adverse events occurring between the date of first drug intake and 28 days after last drug intake, regardless of which treatment group the patient was randomized to.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
Arm/Group Description	Weeks 1-24: Oxaliplatin was adminis...	Weeks 1-24: Bevacizumab 5 mg/kg was...	Weeks 1-24: Bevacizumab 7.5 mg/kg w...
Arm/Group Description	Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with Leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Observation only.	Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).	Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks). Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).
All-Cause Mortality
	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	226/1126 (20.07%)	297/1145 (25.94%)	284/1135 (25.02%)
Blood and lymphatic system disorders
Neutropenia ^† 1	18/1126 (1.60%)	18/1145 (1.57%)	0/1135 (0.00%)
Febrile neutropenia ^† 1	14/1126 (1.24%)	9/1145 (0.79%)	2/1135 (0.18%)
Anaemia ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Idiopathic thrombocytopenia purpura ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Leukopenia ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Thrombocytopenia ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Cardiac disorders
Myocardial infarction ^† 1	1/1126 (0.09%)	5/1145 (0.44%)	1/1135 (0.09%)
Angina pectoris ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	4/1135 (0.35%)
Coronary artery disease ^† 1	1/1126 (0.09%)	2/1145 (0.17%)	1/1135 (0.09%)
Myocardial ischaemia ^† 1	2/1126 (0.18%)	1/1145 (0.09%)	1/1135 (0.09%)
Acute myocardial infarction ^† 1	1/1126 (0.09%)	2/1145 (0.17%)	0/1135 (0.00%)
Cardiac arrest ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	2/1135 (0.18%)
Angina unstable ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Arteriospasm coronary ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	1/1135 (0.09%)
Atrial fibrillation ^† 1	2/1126 (0.18%)	0/1145 (0.00%)	0/1135 (0.00%)
Acute coronary syndrome ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Cardiac asthma ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Cardiac failure ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Cardiac failure congestive ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Left ventricular dysfunction ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Mitral valve incompetence ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Palpitations ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Paroxysmal arrhythmia ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Pericardial haemorrhage ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Sinus arrest ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Ear and labyrinth disorders
Vertigo ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Endocrine disorders
Hypothyroidism ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Eye disorders
Retinal detachment ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Retinal vein thrombosis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Uveitis ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Gastrointestinal disorders
Diarrhoea ^† 1	28/1126 (2.49%)	28/1145 (2.45%)	62/1135 (5.46%)
Abdominal pain ^† 1	11/1126 (0.98%)	14/1145 (1.22%)	18/1135 (1.59%)
Vomiting ^† 1	7/1126 (0.62%)	11/1145 (0.96%)	16/1135 (1.41%)
Intestinal obstruction ^† 1	6/1126 (0.53%)	9/1145 (0.79%)	7/1135 (0.62%)
Nausea ^† 1	0/1126 (0.00%)	4/1145 (0.35%)	7/1135 (0.62%)
Rectal haemorrhage ^† 1	1/1126 (0.09%)	7/1145 (0.61%)	3/1135 (0.26%)
Enteritis ^† 1	3/1126 (0.27%)	0/1145 (0.00%)	5/1135 (0.44%)
Small intestinal obstruction ^† 1	2/1126 (0.18%)	2/1145 (0.17%)	4/1135 (0.35%)
Constipation ^† 1	1/1126 (0.09%)	4/1145 (0.35%)	2/1135 (0.18%)
Subileus ^† 1	1/1126 (0.09%)	4/1145 (0.35%)	2/1135 (0.18%)
Colitis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	5/1135 (0.44%)
Abdominal adhesions ^† 1	2/1126 (0.18%)	0/1145 (0.00%)	2/1135 (0.18%)
Gastritis ^† 1	3/1126 (0.27%)	1/1145 (0.09%)	0/1135 (0.00%)
Gastrointestinal haemorrhage ^† 1	0/1126 (0.00%)	2/1145 (0.17%)	2/1135 (0.18%)
Gastrointestinal obstruction ^† 1	0/1126 (0.00%)	3/1145 (0.26%)	1/1135 (0.09%)
Haemorrhoids ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	2/1135 (0.18%)
Oesophagitis ^† 1	0/1126 (0.00%)	2/1145 (0.17%)	2/1135 (0.18%)
Small intestinal perforation ^† 1	0/1126 (0.00%)	4/1145 (0.35%)	0/1135 (0.00%)
Enterocolitis ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	1/1135 (0.09%)
Ileus paralytic ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	2/1135 (0.18%)
Intestinal perforation ^† 1	1/1126 (0.09%)	2/1145 (0.17%)	0/1135 (0.00%)
Pancreatitis ^† 1	2/1126 (0.18%)	1/1145 (0.09%)	0/1135 (0.00%)
Pancreatitis acute ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	1/1135 (0.09%)
Peritonitis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	2/1135 (0.18%)
Stomatitis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	2/1135 (0.18%)
Abdominal distension ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	1/1135 (0.09%)
Abdominal hernia ^† 1	2/1126 (0.18%)	0/1145 (0.00%)	0/1135 (0.00%)
Anal fissure ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Anal fistula ^† 1	0/1126 (0.00%)	2/1145 (0.17%)	0/1135 (0.00%)
Gastrointestinal necrosis ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Haematemesis ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Haematochezia ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	2/1135 (0.18%)
Ileus ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Mechanical ileus ^† 1	2/1126 (0.18%)	0/1145 (0.00%)	0/1135 (0.00%)
Abdominal discomfort ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Abdominal pain lower ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Abdominal pain upper ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Abdominal rigidity ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Acute abdomen ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Caecitis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Colitis ulcerative ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Crohn's disease ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Duodenitis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Dyspepsia ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Enterocolitis haemorrhagic ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Erosive oesophagitis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Faecaloma ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Food poisoning ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Gastric ulcer ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Gastric volvulus ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Gastrointestinal perforation ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Gastrooesophageal reflux disease ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Hiatus hernia, obstructive ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Ileal perforation ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Intestinal angina ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Intestinal dilatation ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Intestinal fistula ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Intestinal ischaemia ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Intestinal prolapse ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Intestinal strangulation ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Large intestine perforation ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Lower gastrointestinal haemorrhage ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Mallory-Weiss syndrome ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Melaena ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Mesenteric vein thrombosis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Neutropenic colitis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Rectal perforation ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Umbilical hernia ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Upper gastrointestinal haemorrhage ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Volvulus of small bowel ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
General disorders
Pyrexia ^† 1	20/1126 (1.78%)	10/1145 (0.87%)	16/1135 (1.41%)
Non-cardiac chest pain ^† 1	1/1126 (0.09%)	2/1145 (0.17%)	5/1135 (0.44%)
Sudden death ^† 1	0/1126 (0.00%)	2/1145 (0.17%)	3/1135 (0.26%)
Asthenia ^† 1	0/1126 (0.00%)	3/1145 (0.26%)	1/1135 (0.09%)
Chest pain ^† 1	1/1126 (0.09%)	2/1145 (0.17%)	1/1135 (0.09%)
Extravasation ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	2/1135 (0.18%)
Medical device complication ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Multi-organ failure ^† 1	2/1126 (0.18%)	0/1145 (0.00%)	0/1135 (0.00%)
Thrombosis in device ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	1/1135 (0.09%)
Adhesion ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Catheter site pain ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Chills ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Device leakage ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Device malfunction ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
General physical health deterioration ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Hernia obstructive ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Hyperpyrexia ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Infusion site thrombosis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Malaise ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Pain ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Performance status decreased ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Sudden cardiac death ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Visceral pain ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Hepatobiliary disorders
Cholecystitis ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	2/1135 (0.18%)
Portal vein thrombosis ^† 1	1/1126 (0.09%)	2/1145 (0.17%)	1/1135 (0.09%)
Cholangitis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Cholecystitis acute ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Cholelithiasis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Cytolytic hepatitis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Hepatic function abnormal ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Hepatitis toxic ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Hepatotoxicity ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Hyperbilirubinaemia ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Immune system disorders
Drug hypersensitivity ^† 1	5/1126 (0.44%)	3/1145 (0.26%)	1/1135 (0.09%)
Hypersensitivity ^† 1	3/1126 (0.27%)	1/1145 (0.09%)	1/1135 (0.09%)
Anaphylactic reaction ^† 1	0/1126 (0.00%)	3/1145 (0.26%)	0/1135 (0.00%)
Anaphylactic shock ^† 1	2/1126 (0.18%)	0/1145 (0.00%)	1/1135 (0.09%)
Anaphylactiod reaction ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Infections and infestations
Device related infection ^† 1	8/1126 (0.71%)	12/1145 (1.05%)	4/1135 (0.35%)
Pneumonia ^† 1	3/1126 (0.27%)	4/1145 (0.35%)	5/1135 (0.44%)
Urinary tract infection ^† 1	2/1126 (0.18%)	5/1145 (0.44%)	4/1135 (0.35%)
Sepsis ^† 1	4/1126 (0.36%)	3/1145 (0.26%)	3/1135 (0.26%)
Gastroenteritis ^† 1	1/1126 (0.09%)	5/1145 (0.44%)	3/1135 (0.26%)
Infection ^† 1	5/1126 (0.44%)	3/1145 (0.26%)	1/1135 (0.09%)
Abdominal abscess ^† 1	2/1126 (0.18%)	4/1145 (0.35%)	2/1135 (0.18%)
Catheter site infection ^† 1	4/1126 (0.36%)	4/1145 (0.35%)	0/1135 (0.00%)
Neutropenic sepsis ^† 1	4/1126 (0.36%)	1/1145 (0.09%)	1/1135 (0.09%)
Lower respiratory tract infection ^† 1	3/1126 (0.27%)	2/1145 (0.17%)	0/1135 (0.00%)
Anal abscess ^† 1	0/1126 (0.00%)	3/1145 (0.26%)	1/1135 (0.09%)
Cellulitis ^† 1	3/1126 (0.27%)	0/1145 (0.00%)	1/1135 (0.09%)
Abdominal wall abscess ^† 1	0/1126 (0.00%)	2/1145 (0.17%)	1/1135 (0.09%)
Device related sepsis ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	1/1135 (0.09%)
Staphylococcal sepsis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	2/1135 (0.18%)
Abscess ^† 1	0/1126 (0.00%)	2/1145 (0.17%)	0/1135 (0.00%)
Erysipelas ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Herpes zoster ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	1/1135 (0.09%)
Neutropenic infection ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Pelvic abscess ^† 1	0/1126 (0.00%)	2/1145 (0.17%)	0/1135 (0.00%)
Septic shock ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Upper respiratory tract infection ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Viral infection ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Abdominal infection ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Appendicitis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Appendicitis perforated ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Aspergillosis ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Bacteraemia ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Bronchopneumonia ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Bronchopulmonary aspergillosis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Campylobacter infection ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Candida sepsis ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Catheter site cellulitis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Cholecystitis infective ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Clostridial infection ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Clostridium difficile colitis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Diverticulitis ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Enteritis infection ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Gastroenteritis norovirus ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Gastroenteritis viral ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Hepatitis viral ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Herpes zoster ophthalmic ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Incision site cellulitis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Intervertebral discitis ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Intestinal fistual infection ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Klebsiella bacteraemia ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Klebsiella infection ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Lower respiratory tract infection viral ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Oral candidiasis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Orchitis ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Overgrowth bacterial ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Perineal abscess ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Pharyngitis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Post procedural infection ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Postoperative abscess ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Psoas abscess ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Puncture site infection ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Respiratory tract infection ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Skin infection ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Staphylococcal bacteraemia ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Subcutaneous abscess ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Tooth abscess ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Tuberculosis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Wound abscess ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Wound infection ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Injury, poisoning and procedural complications
Incisional hernia ^† 1	1/1126 (0.09%)	2/1145 (0.17%)	2/1135 (0.18%)
Procedural site reaction ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	2/1135 (0.18%)
Accident at work ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Anastomotic stenosis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Brachial plexus injury ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Cervical vertebral fracture ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Drug toxicity ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Fall ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Foot fracture ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Femur fracture ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Head injury ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Joint dislocation ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Multiple fractures ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Post procedural fistula ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Post procedural haemorrhage ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Road traffic accident ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Subdural haematoma ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Thoracic vertebral fracture ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Tibia fracture ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Investigations
Blood lactate dehydrogenase increased ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	1/1135 (0.09%)
Blood creatinine increased ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Blood glucose fluctuation ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Weight increased ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Metabolism and nutrition disorders
Dehydration ^† 1	7/1126 (0.62%)	10/1145 (0.87%)	17/1135 (1.50%)
Hyperglycaemia ^† 1	3/1126 (0.27%)	4/1145 (0.35%)	2/1135 (0.18%)
Hypokalaemia ^† 1	2/1126 (0.18%)	3/1145 (0.26%)	2/1135 (0.18%)
Decreased appetite ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	2/1135 (0.18%)
Hypertriglyceridaemia ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Hypocalcaemia ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Hyponatraemia ^† 1	0/1126 (0.00%)	2/1145 (0.17%)	0/1135 (0.00%)
Diabetes mellitus ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Diabetic ketoacidosis ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Gout ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Hypercholesterolaemia ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Hypomagnesaemia ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	1/1135 (0.09%)
Intervertebral disc protusion ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Muscle spasms ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Muscular weakness ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Musculoskeletal chest pain ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Musculoskeletal disorder ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Myalgia ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Pain in extremity ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	1/1135 (0.09%)
Benign lung neoplasm ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Nervous system disorders
Syncope ^† 1	2/1126 (0.18%)	5/1145 (0.44%)	1/1135 (0.09%)
Transient ischaemic attack ^† 1	1/1126 (0.09%)	3/1145 (0.26%)	2/1135 (0.18%)
Cerebrovascular accident ^† 1	0/1126 (0.00%)	2/1145 (0.17%)	1/1135 (0.09%)
Neuropathy peripheral ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	1/1135 (0.09%)
Convulsion ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Dizziness ^† 1	2/1126 (0.18%)	0/1145 (0.00%)	0/1135 (0.00%)
Epilepsy ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	2/1135 (0.18%)
Headache ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Ischaemic stroke ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	2/1135 (0.18%)
Peripheral sensory neuropathy ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Cerebral ischaemia ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Dysaesthesia ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Encephalopathy ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Leukoaraiosis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Loss of consciousness ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Migraine ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Monoparesis ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Neurotoxicity ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Orthostatic intolerance ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Paraesthesia ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Post herpetic neuralgia ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Reversible ischaemic neurological deficit ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Reversible posterior leukoencephalopathy syndrome ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Sensory disturbance ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Somnolence ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Speech disorder ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Psychiatric disorders
Depression ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Alcoholism ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Anxiety ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Renal and urinary disorders
Hydronephrosis ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	1/1135 (0.09%)
Renal failure acute ^† 1	2/1126 (0.18%)	1/1145 (0.09%)	0/1135 (0.00%)
Renal failure ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Renal impairment ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	1/1135 (0.09%)
Ureteric stenosis ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Acute prerenal failure ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Calculus ureteric ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Calculus urinary ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Nephrogenic diabetes insipidus ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Nephrotic syndrome ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Reproductive system and breast disorders
Female genital tract fistula ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Prostatitis ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Vaginal haemorrhage ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism ^† 1	11/1126 (0.98%)	15/1145 (1.31%)	10/1135 (0.88%)
Dyspnoea ^† 1	2/1126 (0.18%)	3/1145 (0.26%)	2/1135 (0.18%)
Epistaxis ^† 1	0/1126 (0.00%)	3/1145 (0.26%)	1/1135 (0.09%)
Bronchospasm ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	2/1135 (0.18%)
Dysaesthesia pharynx ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	3/1135 (0.26%)
Laryngospasm ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	3/1135 (0.26%)
Pneumothorax ^† 1	1/1126 (0.09%)	2/1145 (0.17%)	0/1135 (0.00%)
Respiratory failure ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	2/1135 (0.18%)
Acute respiratory distress syndrome ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Interstitial lung disease ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Organising pneumonia ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Pneumonia aspiration ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Pulmonary artery thrombosis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Pulmonary oedema ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Skin and subcutaneous tissue disorders
Angioedema ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Drug eruption ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Palmar-Plantar ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Swelling face ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Urticaria ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Social circumstances
Pregnancy of partner ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Surgical and medical procedures
Central venous catheter removal ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Vascular disorders
Deep vein thrombosis ^† 1	9/1126 (0.80%)	16/1145 (1.40%)	12/1135 (1.06%)
Hypertension ^† 1	1/1126 (0.09%)	2/1145 (0.17%)	13/1135 (1.15%)
Venous thrombosis ^† 1	3/1126 (0.27%)	5/1145 (0.44%)	1/1135 (0.09%)
Jugular vein thrombosis ^† 1	2/1126 (0.18%)	3/1145 (0.26%)	0/1135 (0.00%)
Subclavian vein thrombosis ^† 1	1/1126 (0.09%)	2/1145 (0.17%)	2/1135 (0.18%)
Venous thrombosis limb ^† 1	0/1126 (0.00%)	3/1145 (0.26%)	2/1135 (0.18%)
Hypertensive crisis ^† 1	0/1126 (0.00%)	3/1145 (0.26%)	1/1135 (0.09%)
Hypotension ^† 1	0/1126 (0.00%)	2/1145 (0.17%)	1/1135 (0.09%)
Thrombophlebitis ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Thrombosis ^† 1	1/1126 (0.09%)	1/1145 (0.09%)	0/1135 (0.00%)
Arterial stenosis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Arterial thrombosis ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Arterial thrombosis limb ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Axillary vein thrombosis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Pelvic venous thrombosis ^† 1	0/1126 (0.00%)	0/1145 (0.00%)	1/1135 (0.09%)
Peripheral ischaemia ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
Phlebitis ^† 1	0/1126 (0.00%)	1/1145 (0.09%)	0/1135 (0.00%)
Thrombophlebitis superficial ^† 1	1/1126 (0.09%)	0/1145 (0.00%)	0/1135 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (13.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	FOLFOX4	FOLFOX4 + Bv	XELOX+Bv
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1112/1126 (98.76%)	1127/1145 (98.43%)	1117/1135 (98.41%)
Blood and lymphatic system disorders
Neutropenia ^† 1	660/1126 (58.61%)	567/1145 (49.52%)	273/1135 (24.05%)
Thrombocytopenia ^† 1	331/1126 (29.40%)	115/1145 (10.04%)	99/1135 (8.72%)
Anaemia ^† 1	116/1126 (10.30%)	89/1145 (7.77%)	74/1135 (6.52%)
Leukopenia ^† 1	79/1126 (7.02%)	55/1145 (4.80%)	34/1135 (3.00%)
Eye disorders
Lacrimation increased ^† 1	70/1126 (6.22%)	69/1145 (6.03%)	35/1135 (3.08%)
Gastrointestinal disorders
Nausea ^† 1	725/1126 (64.39%)	761/1145 (66.46%)	720/1135 (63.44%)
Diarrhoea ^† 1	620/1126 (55.06%)	699/1145 (61.05%)	699/1135 (61.59%)
Vomiting ^† 1	385/1126 (34.19%)	394/1145 (34.41%)	460/1135 (40.53%)
Stomatitis ^† 1	310/1126 (27.53%)	360/1145 (31.44%)	246/1135 (21.67%)
Constipation ^† 1	308/1126 (27.35%)	324/1145 (28.30%)	219/1135 (19.30%)
Abdominal pain ^† 1	220/1126 (19.54%)	227/1145 (19.83%)	214/1135 (18.85%)
Dyspepsia ^† 1	126/1126 (11.19%)	162/1145 (14.15%)	84/1135 (7.40%)
Abdominal pain upper ^† 1	86/1126 (7.64%)	118/1145 (10.31%)	113/1135 (9.96%)
Haemorrhoids ^† 1	29/1126 (2.58%)	68/1145 (5.94%)	41/1135 (3.61%)
General disorders
Fatigue ^† 1	404/1126 (35.88%)	425/1145 (37.12%)	355/1135 (31.28%)
Asthenia ^† 1	241/1126 (21.40%)	251/1145 (21.92%)	250/1135 (22.03%)
Pyrexia ^† 1	186/1126 (16.52%)	185/1145 (16.16%)	106/1135 (9.34%)
Mucosal inflammation ^† 1	85/1126 (7.55%)	85/1145 (7.42%)	57/1135 (5.02%)
Temperature intolerance ^† 1	61/1126 (5.42%)	61/1145 (5.33%)	50/1135 (4.41%)
Oedema peripheral ^† 1	54/1126 (4.80%)	62/1145 (5.41%)	45/1135 (3.96%)
Immune system disorders
Drug hypersensitivity ^† 1	66/1126 (5.86%)	72/1145 (6.29%)	32/1135 (2.82%)
Infections and infestations
Nasopharyngitis ^† 1	76/1126 (6.75%)	92/1145 (8.03%)	70/1135 (6.17%)
Upper respiratory tract infection ^† 1	52/1126 (4.62%)	87/1145 (7.60%)	55/1135 (4.85%)
Investigations
Weight increased ^† 1	58/1126 (5.15%)	81/1145 (7.07%)	68/1135 (5.99%)
Weight decreased ^† 1	26/1126 (2.31%)	56/1145 (4.89%)	61/1135 (5.37%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	268/1126 (23.80%)	324/1145 (28.30%)	295/1135 (25.99%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	63/1126 (5.60%)	140/1145 (12.23%)	122/1135 (10.75%)
Pain in extremity ^† 1	63/1126 (5.60%)	78/1145 (6.81%)	116/1135 (10.22%)
Back pain ^† 1	79/1126 (7.02%)	87/1145 (7.60%)	66/1135 (5.81%)
Musculoskeletal pain ^† 1	35/1126 (3.11%)	86/1145 (7.51%)	46/1135 (4.05%)
Myalgia ^† 1	39/1126 (3.46%)	70/1145 (6.11%)	56/1135 (4.93%)
Nervous system disorders
Peripheral sensory neuropathy ^† 1	430/1126 (38.19%)	430/1145 (37.55%)	436/1135 (38.41%)
Paraesthesia ^† 1	310/1126 (27.53%)	328/1145 (28.65%)	314/1135 (27.67%)
Neuropathy peripheral ^† 1	252/1126 (22.38%)	234/1145 (20.44%)	204/1135 (17.97%)
Headache ^† 1	169/1126 (15.01%)	284/1145 (24.80%)	219/1135 (19.30%)
Dysgeusia ^† 1	237/1126 (21.05%)	222/1145 (19.39%)	152/1135 (13.39%)
Dysaesthesia ^† 1	128/1126 (11.37%)	106/1145 (9.26%)	128/1135 (11.28%)
Dizziness ^† 1	102/1126 (9.06%)	117/1145 (10.22%)	79/1135 (6.96%)
Neurotoxicity ^† 1	60/1126 (5.33%)	69/1145 (6.03%)	50/1135 (4.41%)
Lethargy ^† 1	44/1126 (3.91%)	50/1145 (4.37%)	59/1135 (5.20%)
Psychiatric disorders
Insomnia ^† 1	135/1126 (11.99%)	132/1145 (11.53%)	91/1135 (8.02%)
Anxiety ^† 1	45/1126 (4.00%)	60/1145 (5.24%)	61/1135 (5.37%)
Renal and urinary disorders
Proteinuria ^† 1	19/1126 (1.69%)	73/1145 (6.38%)	69/1135 (6.08%)
Respiratory, thoracic and mediastinal disorders
Epistaxis ^† 1	228/1126 (20.25%)	424/1145 (37.03%)	216/1135 (19.03%)
Cough ^† 1	86/1126 (7.64%)	120/1145 (10.48%)	41/1135 (3.61%)
Dyspnoea ^† 1	57/1126 (5.06%)	74/1145 (6.46%)	73/1135 (6.43%)
Dysphonia ^† 1	17/1126 (1.51%)	91/1145 (7.95%)	74/1135 (6.52%)
Dysaesthesia pharynx ^† 1	37/1126 (3.29%)	28/1145 (2.45%)	79/1135 (6.96%)
Oropharyngeal pain ^† 1	52/1126 (4.62%)	59/1145 (5.15%)	33/1135 (2.91%)
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome ^† 1	98/1126 (8.70%)	119/1145 (10.39%)	435/1135 (38.33%)
Alopecia ^† 1	231/1126 (20.52%)	241/1145 (21.05%)	73/1135 (6.43%)
Rash ^† 1	114/1126 (10.12%)	112/1145 (9.78%)	110/1135 (9.69%)
Dry skin ^† 1	52/1126 (4.62%)	66/1145 (5.76%)	50/1135 (4.41%)
Pruritus ^† 1	36/1126 (3.20%)	65/1145 (5.68%)	28/1135 (2.47%)
Vascular disorders
Hypertension ^† 1	196/1126 (17.41%)	472/1145 (41.22%)	468/1135 (41.23%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (13.0)

Limitations and Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Medical Communications
Organization:	Hoffman-LaRoche
Phone:	800-821-8590

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gallois C, Shi Q, Meyers JP, Iveson T, Alberts SR, de Gramont A, Sobrero AF, Haller DG, Oki E, Shields AF, Goldberg RM, Kerr R, Lonardi S, Yothers G, Kelly C, Boukovinas I, Labianca R, Sinicrope FA, Souglakos I, Yoshino T, Meyerhardt JA, Andre T, Papamichael D, Taieb J. Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials. J Clin Oncol. 2023 Feb 1;41(4):803-815. doi: 10.1200/JCO.21.02726. Epub 2022 Oct 28.

Cohen R, Taieb J, Fiskum J, Yothers G, Goldberg R, Yoshino T, Alberts S, Allegra C, de Gramont A, Seitz JF, O'Connell M, Haller D, Wolmark N, Erlichman C, Zaniboni A, Lonardi S, Kerr R, Grothey A, Sinicrope FA, Andre T, Shi Q. Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials. J Clin Oncol. 2021 Feb 20;39(6):642-651. doi: 10.1200/JCO.20.01600. Epub 2020 Dec 23.

Chibaudel B, Henriques J, Rakez M, Brenner B, Kim TW, Martinez-Villacampa M, Gallego-Plazas J, Cervantes A, Shim K, Jonker D, Guerin-Meyer V, Mineur L, Banzi C, Dewdney A, Dejthevaporn T, Bloemendal HJ, Roth A, Moehler M, Aranda E, Van Cutsem E, Tabernero J, Schmoll HJ, Hoff PM, Andre T, de Gramont A. Association of Bevacizumab Plus Oxaliplatin-Based Chemotherapy With Disease-Free Survival and Overall Survival in Patients With Stage II Colon Cancer: A Secondary Analysis of the AVANT Trial. JAMA Netw Open. 2020 Oct 1;3(10):e2020425. doi: 10.1001/jamanetworkopen.2020.20425. Erratum In: JAMA Netw Open. 2021 Feb 1;4(2):e210700.

Salem ME, Yin J, Goldberg RM, Pederson LD, Wolmark N, Alberts SR, Taieb J, Marshall JL, Lonardi S, Yoshino T, Kerr RS, Yothers G, Grothey A, Andre T, De Gramont A, Shi Q. Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the ACCENT database. Ann Oncol. 2020 Apr;31(4):480-486. doi: 10.1016/j.annonc.2019.12.007. Epub 2020 Jan 16.

Andre T, Vernerey D, Im SA, Bodoky G, Buzzoni R, Reingold S, Rivera F, McKendrick J, Scheithauer W, Ravit G, Fountzilas G, Yong WP, Isaacs R, Osterlund P, Liang JT, Creemers GJ, Rakez M, Van Cutsem E, Cunningham D, Tabernero J, de Gramont A. Bevacizumab as adjuvant treatment of colon cancer: updated results from the S-AVANT phase III study by the GERCOR Group. Ann Oncol. 2020 Feb;31(2):246-256. doi: 10.1016/j.annonc.2019.12.006. Epub 2019 Dec 18.

Taieb J, Shi Q, Pederson L, Alberts S, Wolmark N, Van Cutsem E, de Gramont A, Kerr R, Grothey A, Lonardi S, Yoshino T, Yothers G, Sinicrope FA, Zaanan A, Andre T. Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an ACCENT pooled analysis of seven studies. Ann Oncol. 2019 Sep 1;30(9):1466-1471. doi: 10.1093/annonc/mdz208.

de Gramont A, Van Cutsem E, Schmoll HJ, Tabernero J, Clarke S, Moore MJ, Cunningham D, Cartwright TH, Hecht JR, Rivera F, Im SA, Bodoky G, Salazar R, Maindrault-Goebel F, Shacham-Shmueli E, Bajetta E, Makrutzki M, Shang A, Andre T, Hoff PM. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol. 2012 Dec;13(12):1225-33. doi: 10.1016/S1470-2045(12)70509-0. Epub 2012 Nov 16.

Layout table for additonal information

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT00112918
Other Study ID Numbers:	CDR0000427299 P30CA016042 ( U.S. NIH Grant/Contract ) UCLA-0412086-01 ROCHE-BO17920A
First Submitted:	June 2, 2005
First Posted:	June 3, 2005
Results First Submitted:	June 1, 2012
Results First Posted:	September 6, 2012
Last Update Posted:	August 27, 2013

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