Study of Bevacizumab + mFOLFOX6 Versus Bevacizumab + FOLF... | NCT01374425

NCT01374425

ID	Type	Description	Link
2011-004755-39	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Bevacizumab + mFOLFOX6	Experimental	Participants will receive bevacizumab plus mFOLFOX6 by intravenous (IV) infusion on Day 1 of each 2-week cycle until disease progression or unacceptable toxicity. Participants may be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin, with bevacizumab continued in 3-week cycles.	Drug: 5-Fluorouracil Drug: Bevacizumab Drug: Leucovorin Drug: Oxaliplatin Drug: Capecitabine
Bevacizumab + FOLFIRI	Experimental	Participants will receive bevacizumab plus FOLFIRI by IV infusion on Day 1 of each 2-week cycle until disease progression or unacceptable toxicity. Participants may be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan, with bevacizumab continued in 3-week cycles.	Drug: 5-Fluorouracil Drug: Bevacizumab Drug: Irinotecan Drug: Leucovorin Drug: Capecitabine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
5-Fluorouracil	Drug	5-Fluorouracil 400 milligrams per meter-squared (mg/m^2) by IV bolus and subsequent 2400 mg/m^2 by IV infusion over 46 hours will be administered every 2 weeks until disease progression or unacceptable toxicity.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as greater than or equal to (≥) 20 percent (%) increase in sum of largest diameters (LD) of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 millimeters (mm). Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% confidence interval (CI) was computed using the method of Brookmeyer and Crowley.	From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels	Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.	From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels	Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Secondary Outcomes

Measure	Description	Time Frame
PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and High VEGF-A Levels	Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed colorectal cancer (CRC) with at least one measurable metastatic lesion by RECIST Version 1.1
Archival tumor tissue sample must be requested and available prior to study entry. If no archival tumor tissue sample is available, a fresh biopsy tissue sample must be obtained but should be discussed first with the medical monitor. A copy of the local pathology report must be submitted along with the specimens.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Participants with treated brain metastases are eligible for study participation. Participants may not receive ongoing treatment with steroids at Screening. Anticonvulsants (at stable dose) are allowed. Treatment for brain metastases may be whole-brain radiotherapy, radiosurgery, neurosurgery, or a combination as deemed appropriate by the treating physician. Radiotherapy and stereotactic radiosurgery must be completed at least 28 days prior to randomization.
Female participants should not be pregnant or breastfeeding. Female participants with childbearing potential should agree to use effective, non-hormonal means of contraception during the study and for a period of at least 6 months following the last administration of study drugs. Female participants with an intact uterus (unless amenorrheic for the last 24 months) must have a negative serum pregnancy test within 7 days prior to randomization into the study.
Male participants must agree to use effective contraception during the study and for a period of at least 6 months following the last administration of study drugs, even if they have been surgically sterilized.

Exclusion Criteria:

Any prior systemic treatment for mCRC
Adjuvant chemotherapy for CRC completed <12 months
Evidence of Gilbert's syndrome or of homozygosity for the UGT1A1*28 allele
Known positivity for human immunodeficiency virus (HIV)
Malignancies other than mCRC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
Radiotherapy to any site for any reason within 28 days prior to randomization, except for palliative radiotherapy to bone lesions within 14 days prior to randomization
Clinically detectable third-space fluid collections that cannot be controlled by drainage or other procedures prior to study entry
Treatment with any other investigational agent, or participation in another investigational drug trial within 28 days prior to randomization

Name	Affiliation	Role
Christiane Langer, M.D.	Genentech, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Birmingham	Alabama	35294	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Bevacizumab + mFOLFOX6	Participants with untreated metastatic colorectal cancer (mCRC) who were candidates for first-line therapy received bevacizumab plus leucovorin, 5-fluorouracil, and oxaliplatin (mFOLFOX6) until disease progression or unacceptable toxicity. Bevacizumab was given as 5 milligrams per kilogram (mg/kg), leucovorin as 400 milligrams per meter-squared (mg/m^2), oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via intravenous (IV) infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Bevacizumab + mFOLFOX6	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
BG001	Bevacizumab + FOLFIRI	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as greater than or equal to (≥) 20 percent (%) increase in sum of largest diameters (LD) of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 millimeters (mm). Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% confidence interval (CI) was computed using the method of Brookmeyer and Crowley.

Intent-to-treat (ITT) Population

Posted

Median

95% Confidence Interval

months

From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
OG001	Bevacizumab + FOLFIRI	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.

Units	Counts
Participants	OG000188 OG001188

Title

Denominators

Categories

Title	Measurements
	OG00010.09(8.80 to 11.56) OG00112.55(10.48 to 14.29)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis stratified by high/low excision repair cross-complementing (ERCC)-1 level and region of enrollment.	Log Rank		0.0555	P-value (relative to Bevacizumab + mFOLFOX6) based on two-sided stratified log rank test and not adjusted for multiple comparisons.	Hazard Ratio (HR)	0.79			2-Sided	95	0.61	1.01			Hazard ratio (HR) (relative to Bevacizumab + mFOLFOX6) was estimated by Cox regression.	No	Superiority or Other

Primary

PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels

Tumor assessments were performed according to RECIST Version 1.1. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to the smallest sum of LD on study, in addition to an absolute increase ≥5 mm. Disease progression was further defined as the last documented progression determined by the Investigator no later than 1 day before initiation of second-line therapy. Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. PFS was defined as the time from randomization to death or disease progression, whichever occurred first. The median duration of PFS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level greater than (>) 1.7 × 10^-3 ERCC-1/B-actin messenger ribonucleic acid (mRNA) at Baseline were included in separate analyses.

Primary

PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 Low)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level less than or equal to (≤) 1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Primary

PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Primary

PFS According to RECIST Version 1.1 in Participants With High Vascular Endothelial Growth Factor (VEGF)-A Levels Versus Participants With Low VEGF-A Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (VEGF-A High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with VEGF-A level >5 picograms per milliliter (pg/mL) at Baseline were included in separate analyses.

Secondary

PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and High VEGF-A Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 High, VEGF-A High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA and VEGF-A level >5 pg/mL at Baseline were included in separate analyses.

Secondary

PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and Low VEGF-A Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 High, VEGF-A Low)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA and VEGF-A level ≤5 pg/mL at Baseline were included in separate analyses.

Secondary

PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 and High VEGF-A Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 Low, VEGF-A High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level ≤1.7 × 10^-3 ERCC-1/B-actin mRNA and VEGF-A level >5 pg/mL at Baseline were included in separate analyses.

Secondary

PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 and Low VEGF-A Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 Low, VEGF-A Low)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level ≤1.7 × 10^-3 ERCC-1/B-actin mRNA and VEGF-A level ≤5 pg/mL at Baseline were included in separate analyses.

Secondary

Overall Survival (OS)

Death on study included death from any cause occurring no later than 3 months after the last component of study treatment. OS was defined as the time from randomization to death. The median duration of OS was estimated by Kaplan-Meier analysis and expressed in months. The 95% CI was computed using the method of Brookmeyer and Crowley.

ITT Population

Posted

Median

95% Confidence Interval

months

From Baseline until death (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
OG001	Bevacizumab + FOLFIRI	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.

Secondary

OS in Participants With High ERCC-1 Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.
OG001	Bevacizumab + FOLFIRI (ERCC-1 High)

Secondary

OS in Participants With Low ERCC-1 Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 Low)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level ≤1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.
OG001	Bevacizumab + FOLFIRI (ERCC-1 Low)

Secondary

OS in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Objective Response According to RECIST Version 1.1

Objective response was defined as complete response (CR) or partial response (PR) according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to less than (<) 10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.

ITT Population

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
OG001	Bevacizumab + FOLFIRI

Secondary

Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High ERCC-1 Levels

Objective response was defined as CR or PR according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. The percentage of participants with CR or PR was reported. The 95% CI was computed using normal approximation to the binomial distribution.

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 Low)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level ≤1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Disease Control According to RECIST Version 1.1

Disease control was defined as CR, PR, or stable disease (SD) according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.

ITT Population

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.

Secondary

Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High ERCC-1 Levels

Disease control was defined as CR, PR, or SD according to RECIST Version 1.1. CR was defined as disappearance of all target lesions and short-axis reduction to <10 mm of any pathological lymph nodes. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to sum of LD at Baseline. Confirmation of response at a consecutive assessment was not required. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for disease progression (≥20% increase in sum of LD of target lesions plus absolute increase ≥5 mm) in reference to the smallest sum of LD on study. The percentage of participants with CR, PR, or SD was reported. The 95% CI was computed using normal approximation to the binomial distribution.

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 Low)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level ≤1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Liver Metastasis Resection

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. R1 was defined as the presence of exposed tumor or histologically detected tumor cells at the line of transection, or <1 mm microscopic margins. In the case of use of radiofrequency ablation or cryotherapy, the resection was considered as R1. R2 was defined as macroscopic positive margins or incomplete resection at time of surgery. The percentage of participants with resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis.

Posted

Number

95% Confidence Interval

percentage of participants

At time of resective surgery during study (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.

Secondary

Percentage of Participants With Complete Liver Metastasis Resection

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis.

Posted

Number

95% Confidence Interval

percentage of participants

At time of resective surgery during study (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.
OG001	Bevacizumab + FOLFIRI

Secondary

Percentage of Participants With Liver Metastasis Resection in Participants With High ERCC-1 Levels

ITT Population; only those participants with liver or liver plus lymph node metastases were included in the analysis. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

At time of resective surgery during study (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Complete Liver Metastasis Resection in Participants With High ERCC-1 Levels

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Posted

Number

95% Confidence Interval

percentage of participants

At time of resective surgery during study (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Liver Metastasis Resection in Participants With Low ERCC-1 Levels

Posted

Number

95% Confidence Interval

percentage of participants

At time of resective surgery during study (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 Low)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level ≤1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Complete Liver Metastasis Resection in Participants With Low ERCC-1 Levels

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Posted

Number

95% Confidence Interval

percentage of participants

At time of resective surgery during study (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX6 (ERCC-1 Low)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level ≤1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Liver Metastasis Resection in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels

Posted

Number

95% Confidence Interval

percentage of participants

At time of resective surgery during study (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Complete Liver Metastasis Resection in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Posted

Number

95% Confidence Interval

percentage of participants

At time of resective surgery during study (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (ERCC-1 High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with ERCC-1 level >1.7 × 10^-3 ERCC-1/B-actin mRNA at Baseline were included in separate analyses.

Secondary

PFS According to RECIST Version 1.1 in Participants With Wild-Type V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Versus Participants With Mutant KRAS

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (KRAS Wild-Type)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with wild-type KRAS at Baseline were included in separate analyses.

Secondary

OS in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (VEGF-A High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with VEGF-A level >5 pg/mL at Baseline were included in separate analyses.
OG001

Secondary

OS in Participants With Wild-Type KRAS Versus Participants With Mutant KRAS

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Median

95% Confidence Interval

months

From Baseline until death (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (KRAS Wild-Type)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with wild-type KRAS at Baseline were included in separate analyses.
OG001

Secondary

Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (VEGF-A High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with VEGF-A level >5 pg/mL at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With Wild-Type KRAS Versus Participants With Mutant KRAS

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (KRAS Wild-Type)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with wild-type KRAS at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels

ITT Population. The "Number of Participants Analyzed" reflects the number of evaluable participants for the outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (VEGF-A High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with VEGF-A level >5 pg/mL at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Liver Metastasis Resection in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels

Posted

Number

95% Confidence Interval

percentage of participants

At time of resective surgery during study (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (VEGF-A High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with VEGF-A level >5 pg/mL at Baseline were included in separate analyses.

Secondary

Percentage of Participants With Complete Liver Metastasis Resection in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels

The timing of resective surgery was not defined in the protocol and was left at the discretion of the Investigator. Resection was classified as R0, R1, or R2 following surgery. R0 was defined as complete resection with clear margins ≥1 mm. The percentage of participants with R0 resection of liver or liver plus lymph node metastases was reported. The 95% CI was computed using normal approximation to the binomial distribution.

Posted

Number

95% Confidence Interval

percentage of participants

At time of resective surgery during study (maximum up to 45 months overall)

ID	Title	Description
OG000	Bevacizumab + mFOLFOX/FOLFIRI (VEGF-A High)	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 or bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Depending on the regimen to which the participant was randomized, bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin or irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles. Participants with VEGF-A level >5 pg/mL at Baseline were included in separate analyses.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Bevacizumab + mFOLFOX6	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus mFOLFOX6 until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, oxaliplatin as 85 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to oxaliplatin and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.			79	185	185	185
EG001	Bevacizumab + FOLFIRI	Participants with untreated mCRC who were candidates for first-line therapy received bevacizumab plus FOLFIRI until disease progression or unacceptable toxicity. Bevacizumab was given as 5 mg/kg, leucovorin as 400 mg/m^2, irinotecan as 180 mg/m^2, and 5-fluorouracil as 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous 46-hour infusion. All treatments were administered via IV infusion and started on Day 1 of each 2-week cycle. Participants could be transitioned to oral capecitabine in the event of unacceptable toxicity to irinotecan and given as 850 or 1000 mg/m^2 twice a day on Days 1 to 14, with bevacizumab continued in 3-week cycles.			87	183	181	183

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0006 affected185 at risk EG0012 affected183 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0005 affected185 at risk EG0016 affected183 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0004 affected185 at risk EG0010 affected183 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0003 affected185 at risk EG0017 affected183 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0003 affected185 at risk EG0013 affected183 at risk
Vomiting	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0003 affected185 at risk EG0014 affected183 at risk
Constipation	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0010 affected183 at risk
Dysphagia	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0010 affected183 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0011 affected183 at risk
Nausea	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0011 affected183 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0010 affected183 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0010 affected183 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Ascites	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Enteritis	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Ileal perforation	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Large intestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Neutropenic colitis	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Oesophageal motility disorder	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Pneumoperitoneum	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Small intestinal perforation	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0012 affected183 at risk
Anal fistula	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Colitis	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0012 affected183 at risk
Duodenitis	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Enterovesical fistula	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Ileus	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0012 affected183 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0012 affected183 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Reflux gastritis	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Sepsis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0004 affected185 at risk EG0013 affected183 at risk
Pneumonia	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0003 affected185 at risk EG0017 affected183 at risk
Cellulitis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0010 affected183 at risk
Septic shock	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0011 affected183 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0010 affected183 at risk
Abdominal abscess	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Abdominal infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Appendicitis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Bronchitis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Candida sepsis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Diverticulitis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Endocarditis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Lung infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Respiratory tract infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Subcutaneous abscess	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Urinary tract infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Urosepsis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Device related infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0012 affected183 at risk
Gastroenteritis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Kidney infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Neutropenic sepsis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Perineal abscess	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Pneumonia bacterial	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Pneumonia parainfluenzae viral	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0009 affected185 at risk EG0019 affected183 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0011 affected183 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0010 affected183 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Pulmonary thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Pulmonary artery thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0008 affected185 at risk EG0015 affected183 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0012 affected183 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Metabolic alkalosis	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Chest pain	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0003 affected185 at risk EG0014 affected183 at risk
Pyrexia	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0003 affected185 at risk EG0014 affected183 at risk
Device dislocation	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0011 affected183 at risk
Asthenia	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Chills	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Mucosal inflammation	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Multi-organ failure	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Peripheral swelling	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Device malfunction	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Fatigue	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0013 affected183 at risk
Gait disturbance	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Localised oedema	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Hypotension	Vascular disorders	MedDRA (18.1)	Non-systematic Assessment	EG0005 affected185 at risk EG0011 affected183 at risk
Hypertension	Vascular disorders	MedDRA (18.1)	Non-systematic Assessment	EG0003 affected185 at risk EG0016 affected183 at risk
Arterial thrombosis	Vascular disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0014 affected183 at risk
Embolism venous	Vascular disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Venous thrombosis	Vascular disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Jugular vein thrombosis	Vascular disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Thrombosis	Vascular disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0003 affected185 at risk EG0010 affected183 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0014 affected183 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Immune thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0012 affected183 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Atrial flutter	Cardiac disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Myocardial infarction	Cardiac disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0013 affected183 at risk
Atrial thrombosis	Cardiac disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Stoma site haemorrhage	Injury, poisoning and procedural complications	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Abdominal wound dehiscence	Injury, poisoning and procedural complications	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Intestinal anastomosis complication	Injury, poisoning and procedural complications	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Aphonia	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Ataxia	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Seizure	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Syncope	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0012 affected183 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Thrombotic stroke	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Ischaemic hepatitis	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Biloma	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Cholangitis	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Hepatitis	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Jaundice	Hepatobiliary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Platelet count decreased	Investigations	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG0010 affected183 at risk
Weight decreased	Investigations	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Blood bilirubin increased	Investigations	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0012 affected183 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Polyarthritis	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0010 affected183 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0012 affected183 at risk
Proteinuria	Renal and urinary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Renal failure	Renal and urinary disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Confusional state	Psychiatric disorders	MedDRA (18.1)	Non-systematic Assessment	EG0001 affected185 at risk EG0011 affected183 at risk
Mental status changes	Psychiatric disorders	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0012 affected183 at risk
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk
Colostomy	Surgical and medical procedures	MedDRA (18.1)	Non-systematic Assessment	EG0000 affected185 at risk EG0011 affected183 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00099 affected185 at risk EG001123 affected183 at risk
Nausea	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG000106 affected185 at risk EG001109 affected183 at risk
Constipation	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00063 affected185 at risk EG00165 affected183 at risk
Vomiting	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00058 affected185 at risk EG00157 affected183 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00039 affected185 at risk EG00154 affected183 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00035 affected185 at risk EG00138 affected183 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00017 affected185 at risk EG00118 affected183 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00019 affected185 at risk EG00114 affected183 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00011 affected185 at risk EG00118 affected183 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0008 affected185 at risk EG00115 affected183 at risk
Oral pain	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0008 affected185 at risk EG00114 affected183 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0006 affected185 at risk EG00116 affected183 at risk
Proctalgia	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0007 affected185 at risk EG00113 affected183 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0007 affected185 at risk EG00111 affected183 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0005 affected185 at risk EG00112 affected183 at risk
Dysphagia	Gastrointestinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00010 affected185 at risk EG0012 affected183 at risk
Fatigue	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG000105 affected185 at risk EG001104 affected183 at risk
Mucosal inflammation	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG00037 affected185 at risk EG00151 affected183 at risk
Pyrexia	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG00018 affected185 at risk EG00129 affected183 at risk
Asthenia	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG00021 affected185 at risk EG00118 affected183 at risk
Oedema peripheral	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG00018 affected185 at risk EG00118 affected183 at risk
Temperature intolerance	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG00034 affected185 at risk EG0011 affected183 at risk
Chest pain	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG00015 affected185 at risk EG00110 affected183 at risk
Chills	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG00010 affected185 at risk EG00110 affected183 at risk
Influenza like illness	General disorders	MedDRA (18.1)	Non-systematic Assessment	EG00010 affected185 at risk EG0016 affected183 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG00085 affected185 at risk EG00123 affected183 at risk
Headache	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG00031 affected185 at risk EG00138 affected183 at risk
Dysgeusia	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG00033 affected185 at risk EG00131 affected183 at risk
Paraesthesia	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG00035 affected185 at risk EG00115 affected183 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG00035 affected185 at risk EG00112 affected183 at risk
Dizziness	Nervous system disorders	MedDRA (18.1)	Non-systematic Assessment	EG00015 affected185 at risk EG00128 affected183 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00041 affected185 at risk EG00159 affected183 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00031 affected185 at risk EG00129 affected183 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00028 affected185 at risk EG00126 affected183 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00012 affected185 at risk EG00121 affected183 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00014 affected185 at risk EG00118 affected183 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG0008 affected185 at risk EG00114 affected183 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (18.1)	Non-systematic Assessment	EG00011 affected185 at risk EG0018 affected183 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG00056 affected185 at risk EG00155 affected183 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG00036 affected185 at risk EG00133 affected183 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG00028 affected185 at risk EG00127 affected183 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0009 affected185 at risk EG00123 affected183 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (18.1)	Non-systematic Assessment	EG0008 affected185 at risk EG00115 affected183 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG00026 affected185 at risk EG00161 affected183 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG00027 affected185 at risk EG00126 affected183 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG00019 affected185 at risk EG00126 affected183 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG00024 affected185 at risk EG00118 affected183 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG00018 affected185 at risk EG00113 affected183 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG00011 affected185 at risk EG0019 affected183 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG0002 affected185 at risk EG00110 affected183 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.1)	Non-systematic Assessment	EG00065 affected185 at risk EG00186 affected183 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (18.1)	Non-systematic Assessment	EG00025 affected185 at risk EG00134 affected183 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (18.1)	Non-systematic Assessment	EG00044 affected185 at risk EG00113 affected183 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG00022 affected185 at risk EG00125 affected183 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG00021 affected185 at risk EG00123 affected183 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG00022 affected185 at risk EG00119 affected183 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG00017 affected185 at risk EG00111 affected183 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (18.1)	Non-systematic Assessment	EG0007 affected185 at risk EG00111 affected183 at risk
Weight decreased	Investigations	MedDRA (18.1)	Non-systematic Assessment	EG00033 affected185 at risk EG00129 affected183 at risk
Neutrophil count decreased	Investigations	MedDRA (18.1)	Non-systematic Assessment	EG00033 affected185 at risk EG00123 affected183 at risk
Platelet count decreased	Investigations	MedDRA (18.1)	Non-systematic Assessment	EG00024 affected185 at risk EG0013 affected183 at risk
White blood cell count decreased	Investigations	MedDRA (18.1)	Non-systematic Assessment	EG00015 affected185 at risk EG0019 affected183 at risk
Insomnia	Psychiatric disorders	MedDRA (18.1)	Non-systematic Assessment	EG00029 affected185 at risk EG00135 affected183 at risk
Depression	Psychiatric disorders	MedDRA (18.1)	Non-systematic Assessment	EG00024 affected185 at risk EG00118 affected183 at risk
Anxiety	Psychiatric disorders	MedDRA (18.1)	Non-systematic Assessment	EG00019 affected185 at risk EG00120 affected183 at risk
Hypertension	Vascular disorders	MedDRA (18.1)	Non-systematic Assessment	EG00061 affected185 at risk EG00154 affected183 at risk
Urinary tract infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG00018 affected185 at risk EG00120 affected183 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG00015 affected185 at risk EG00118 affected183 at risk
Sinusitis	Infections and infestations	MedDRA (18.1)	Non-systematic Assessment	EG0009 affected185 at risk EG00113 affected183 at risk
Proteinuria	Renal and urinary disorders	MedDRA (18.1)	Non-systematic Assessment	EG00038 affected185 at risk EG00139 affected183 at risk
Vision blurred	Eye disorders	MedDRA (18.1)	Non-systematic Assessment	EG00013 affected185 at risk EG00112 affected183 at risk
Lacrimation increased	Eye disorders	MedDRA (18.1)	Non-systematic Assessment	EG0004 affected185 at risk EG00110 affected183 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (18.1)	Non-systematic Assessment	EG00015 affected185 at risk EG0018 affected183 at risk
Hypersensitivity	Immune system disorders	MedDRA (18.1)	Non-systematic Assessment	EG00010 affected185 at risk EG0010 affected183 at risk

Ancestor Terms

ID	Term
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D002166	Camptothecin
D000470	Alkaloids
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D003067	Coenzymes
D045762	Enzymes and Coenzymes
D056831	Coordination Complexes
D009930	Organic Chemicals
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Term
D005472	Fluorouracil
D000068258	Bevacizumab
D000077146	Irinotecan
D002955	Leucovorin
D000077150	Oxaliplatin
D000069287	Capecitabine