Trial Outcomes & Findings for A Trial to Compare Oxaliplatin, Folinic Acid (FA) and 5-Fluorouracil (5FU) Combination Chemotherapy (FOLFOX-4) With or Without Cetuximab in the 1st Line Treatment of Metastatic Colorectal Cancer (mCRC) in Chinese Rat Sarcoma Viral Oncogene Homolog (RAS) Wild-type Patients (NCT NCT01228734)

NCT ID: NCT01228734

Last Updated: 2020-01-28

Results Overview

PFS was defined as the duration (in months) from randomization until the first progressive disease (PD) observation as assessed by the Independent Review Committee (IRC) according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.0, or death due to any cause when death occurred within 90 days of randomization or the last tumor assessment, whichever was later. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of the target lesions, taking as references the smallest sum LD since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 553 participants
• Primary outcome timeframe: Baseline up to 333 weeks
• Results posted on: 2020-01-28

Participant Flow

The study was planned to enroll subjects with Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type (wt) tumors.Following modification of approved EU indication of cetuximab,a decision made to amend study population from subjects with KRAS wt tumors to those with RAS wt tumors. All efficacy/safety analysis based on subjects with RAS wt tumor.

First subject first visit/last subject last visit: 30 September 2010/31 Jan 2018. A total of 553 subjects were enrolled in the trial. 504 subjects were randomized in the study, of which 397 were with RAS wt tumors. Participant Flow is presented for the subjects with RAS wt tumors.

Participant milestones

Measure	Cetuximab + FOLFOX4 Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-fluorouracil (5-FU)/folinic acid (FA). Cetuximab was always administered every 7 days with an initial dose of 400 milligram per square meter (mg/m\^2) at 5 milligram per minute (mg/min) and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	FOLFOX4 Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
Overall Study STARTED	193	204
Overall Study Modified Intent-to-treat Population	193	200
Overall Study Modified Safety Population	194	199
Overall Study COMPLETED	193	200
Overall Study NOT COMPLETED	0	4

Reasons for withdrawal

Measure	Cetuximab + FOLFOX4 Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-fluorouracil (5-FU)/folinic acid (FA). Cetuximab was always administered every 7 days with an initial dose of 400 milligram per square meter (mg/m\^2) at 5 milligram per minute (mg/min) and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	FOLFOX4 Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
Overall Study Randomized, but not treated	0	4

Baseline Characteristics

A Trial to Compare Oxaliplatin, Folinic Acid (FA) and 5-Fluorouracil (5FU) Combination Chemotherapy (FOLFOX-4) With or Without Cetuximab in the 1st Line Treatment of Metastatic Colorectal Cancer (mCRC) in Chinese Rat Sarcoma Viral Oncogene Homolog (RAS) Wild-type Patients

Baseline characteristics by cohort

Measure	Cetuximab + FOLFOX-4 n=193 Participants Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m\^2 at 5 mg/min and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	FOLFOX-4 n=200 Participants Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	Total n=393 Participants Total of all reporting groups
Age, Continuous	54.8 years STANDARD_DEVIATION 11.8 • n=5 Participants	55.1 years STANDARD_DEVIATION 11.2 • n=7 Participants	54.9 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	61 Participants n=7 Participants	127 Participants n=5 Participants
Sex: Female, Male Male	127 Participants n=5 Participants	139 Participants n=7 Participants	266 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 333 weeks

Population: MITT population included all subjects with RAS wild-type tumor status who were randomized to study treatment and who received at least 1 dose of study treatment. Subjects were analyzed as randomized.

PFS was defined as the duration (in months) from randomization until the first progressive disease (PD) observation as assessed by the Independent Review Committee (IRC) according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.0, or death due to any cause when death occurred within 90 days of randomization or the last tumor assessment, whichever was later. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of the target lesions, taking as references the smallest sum LD since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.

Outcome measures

Measure	Cetuximab + FOLFOX-4 n=193 Participants Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m\^2 at 5 mg/min and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	FOLFOX-4 n=200 Participants Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
Progression Free Survival (PFS) Time	9.2 months Interval 8.8 to 10.9	7.4 months Interval 5.8 to 7.5

SECONDARY outcome

Timeframe: Baseline up to 333 weeks

Population: MITT population included all subjects with RAS wild-type tumor status who were randomized to study treatment and who received at least 1 dose of study treatment. Subjects were analyzed as randomized.

OS was defined as the time (in months) from randomization to death. For subjects who were still alive at the analysis data cut-off date or who lost to follow-up, survival was censored at the last recorded date that the subject was known to be alive.

Outcome measures

Measure	Cetuximab + FOLFOX-4 n=193 Participants Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m\^2 at 5 mg/min and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	FOLFOX-4 n=200 Participants Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
Overall Survival (OS) Time	20.8 months Interval 16.3 to 23.5	16.5 months Interval 14.8 to 19.5

SECONDARY outcome

Timeframe: Baseline up to 333 weeks

Population: MITT population included all subjects with RAS wild-type tumor status who were randomized to study treatment and who received at least 1 dose of study treatment. Subjects were analyzed as randomized.

The Best ORR was defined as the percentage of subjects having achieved complete response (CR) or partial response (PR) according to RECIST version 1.0 as determined by the IRC. CR: defined as disappearance of all target and all non-target lesions and no new lesions. PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters, no progression of non-target lesions and no new lesions.

Outcome measures

Measure	Cetuximab + FOLFOX-4 n=193 Participants Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m\^2 at 5 mg/min and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	FOLFOX-4 n=200 Participants Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
Best Overall Response Rate (ORR)	66.3 percentage of subjects Interval 59.2 to 72.9	40.5 percentage of subjects Interval 33.6 to 47.7

SECONDARY outcome

Timeframe: Baseline up to 333 weeks

Population: MITT population included all subjects with RAS wild-type tumor status who were randomized to study treatment and who received at least 1 dose of study treatment. Subjects were analyzed as randomized.

TTF was defined as time from randomization to date of the first occurrence of radiologically confirmed PD as determined by IRC, Clinical PD according to the Investigator's assessment (if radiological confirmation of PD by IRC was unavailable), discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death within 90 days of last tumor assessment or randomization. Subjects without event were censored on the date of last tumor assessment.

Outcome measures

Measure	Cetuximab + FOLFOX-4 n=193 Participants Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m\^2 at 5 mg/min and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	FOLFOX-4 n=200 Participants Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
Time to Treatment Failure (TTF)	9.2 months Interval 7.4 to 9.3	5.6 months Interval 5.6 to 6.5

SECONDARY outcome

Timeframe: Baseline up to 333 weeks

Population: MITT population included all subjects with RAS wild-type tumor status who were randomized to study treatment and who received at least 1 dose of study treatment. Subjects were analyzed as randomized. Here "Number Analyzed" signifies those subjects who were evaluable for the specified categories.

The number of subjects who underwent liver metastatic surgery after start of treatment and the outcome of surgery with respect to residual tumor after surgery (R0, R1, R2, not evaluable) were summarized. In case of resection of more than one metastasis, the worst outcome of surgery defined the overall status of a subject. R0 = No residual tumor after resection (all lesions resected completely); R1 = Metastases not resected completely with microscopic residual lesions; and R2 = Metastases not resected completely with macroscopic residual lesions.

Outcome measures

Measure	Cetuximab + FOLFOX-4 n=193 Participants Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m\^2 at 5 mg/min and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	FOLFOX-4 n=200 Participants Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
Number of Subjects With Curative Surgery of Liver Metastases Subjects with liver surgery	9 subjects	6 subjects
Number of Subjects With Curative Surgery of Liver Metastases Subjects with liver surgery outcome: R0	7 subjects	2 subjects
Number of Subjects With Curative Surgery of Liver Metastases Subjects with liver surgery outcome: R1	1 subjects	2 subjects
Number of Subjects With Curative Surgery of Liver Metastases Subjects with liver surgery outcome: R2	0 subjects	0 subjects
Number of Subjects With Curative Surgery of Liver Metastases Subjects not evaluable	0 subjects	0 subjects

Adverse Events

Cetuximab + FOLFOX-4

Serious events: 42 serious events

Other events: 194 other events

Deaths: 157 deaths

FOLFOX-4

Serious events: 27 serious events

Other events: 194 other events

Deaths: 173 deaths

Serious adverse events

Measure	Cetuximab + FOLFOX-4 n=194 participants at risk Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m\^2 at 5 mg/min and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	FOLFOX-4 n=199 participants at risk Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
Blood and lymphatic system disorders BONE MARROW FAILURE	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Blood and lymphatic system disorders LEUKOPENIA	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Blood and lymphatic system disorders NEUTROPENIA	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Blood and lymphatic system disorders THROMBOCYTOPENIA	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	1.0% 2/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Blood and lymphatic system disorders THROMBOCYTOPENIC PURPURA	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Cardiac disorders ATRIAL FLUTTER	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Cardiac disorders VENTRICULAR TACHYCARDIA	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Eye disorders RETINAL DETACHMENT	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders ABDOMINAL PAIN	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders ANAL FISTULA	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders DIARRHOEA	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders ENTERITIS	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders INCARCERATED INGUINAL HERNIA	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders INTESTINAL OBSTRUCTION	3.6% 7/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	2.0% 4/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders INTESTINAL PERFORATION	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders LARGE INTESTINAL OBSTRUCTION	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
General disorders MULTI-ORGAN FAILURE	1.5% 3/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	1.5% 3/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
General disorders PYREXIA	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
General disorders SUDDEN DEATH	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Hepatobiliary disorders CHOLECYSTITIS	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Hepatobiliary disorders HEPATIC FAILURE	1.0% 2/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Hepatobiliary disorders HYPERBILIRUBINAEMIA	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Hepatobiliary disorders JAUNDICE CHOLESTATIC	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Immune system disorders DRUG HYPERSENSITIVITY	1.0% 2/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations ANAL ABSCESS	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations EPIDIDYMITIS	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations INFECTION	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations LOWER RESPIRATORY TRACT INFECTION	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations PNEUMONIA	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations SEPTIC SHOCK	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations SKIN INFECTION	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations STAPHYLOCOCCAL BACTERAEMIA	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations STAPHYLOCOCCAL INFECTION	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations HAEMOGLOBIN DECREASED	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Metabolism and nutrition disorders TYPE 2 DIABETES MELLITUS	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Nervous system disorders CEREBRAL INFARCTION	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	1.0% 2/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Nervous system disorders HEADACHE	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Nervous system disorders HEPATIC ENCEPHALOPATHY	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Nervous system disorders SYNCOPE	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Psychiatric disorders SUICIDE ATTEMPT	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Renal and urinary disorders RENAL FAILURE	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Renal and urinary disorders URETERIC OBSTRUCTION	1.0% 2/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Respiratory, thoracic and mediastinal disorders DYSPNOEA AT REST	1.0% 2/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Vascular disorders AXILLARY VEIN THROMBOSIS	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Vascular disorders DEEP VEIN THROMBOSIS	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Vascular disorders JUGULAR VEIN THROMBOSIS	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Vascular disorders PHLEBITIS	0.00% 0/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	1.0% 2/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Vascular disorders SUBCLAVIAN VEIN THROMBOSIS	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Vascular disorders VENOUS THROMBOSIS LIMB	1.0% 2/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders LARGE INTESTINE POLYP	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations INFUSION SITE INFECTION	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations RESPIRATORY TRACT INFECTION	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations ALANINE AMINOTRANSFERASE INCREASED	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) COLON CANCER METASTATIC	0.52% 1/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.

Other adverse events

Measure	Cetuximab + FOLFOX-4 n=194 participants at risk Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m\^2 at 5 mg/min and 250 mg/m\^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m\^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m\^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.	FOLFOX-4 n=199 participants at risk Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m\^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m\^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m\^2/day intravenously over 2-4 minutes followed by 600 mg/m\^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.
Blood and lymphatic system disorders ANAEMIA	14.4% 28/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	12.1% 24/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Blood and lymphatic system disorders BONE MARROW FAILURE	9.3% 18/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	7.0% 14/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Blood and lymphatic system disorders LEUKOPENIA	77.8% 151/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	73.4% 146/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Blood and lymphatic system disorders NEUTROPENIA	80.4% 156/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	74.9% 149/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Blood and lymphatic system disorders THROMBOCYTOPENIA	47.4% 92/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	51.3% 102/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders ABDOMINAL DISTENSION	10.8% 21/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	6.5% 13/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders ABDOMINAL PAIN	19.1% 37/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	9.5% 19/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders CONSTIPATION	22.2% 43/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	14.6% 29/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders DIARRHOEA	35.6% 69/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	17.6% 35/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	6.2% 12/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	2.5% 5/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders HAEMATOCHEZIA	5.2% 10/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	2.5% 5/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders MOUTH ULCERATION	11.3% 22/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	4.5% 9/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders NAUSEA	36.1% 70/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	46.2% 92/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders STOMATITIS	16.5% 32/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	7.0% 14/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Gastrointestinal disorders VOMITING	22.2% 43/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	26.1% 52/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
General disorders FATIGUE	39.7% 77/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	28.1% 56/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
General disorders PYREXIA	30.4% 59/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	24.1% 48/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Hepatobiliary disorders HYPERBILIRUBINAEMIA	9.8% 19/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	10.6% 21/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Hepatobiliary disorders LIVER INJURY	6.2% 12/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	3.0% 6/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Immune system disorders DRUG HYPERSENSITIVITY	9.3% 18/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	7.5% 15/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations NASOPHARYNGITIS	5.2% 10/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	2.0% 4/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations PARONYCHIA	14.4% 28/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	9.3% 18/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	7.0% 14/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Injury, poisoning and procedural complications INFUSION RELATED REACTION	10.3% 20/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	6.0% 12/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations ALANINE AMINOTRANSFERASE INCREASED	33.5% 65/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	27.1% 54/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	29.9% 58/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	29.1% 58/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations BLOOD ALBUMIN DECREASED	6.2% 12/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	2.0% 4/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	8.2% 16/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	4.0% 8/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations BLOOD BILIRUBIN INCREASED	7.7% 15/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	3.5% 7/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations BLOOD LACTATE DEHYDROGENASE INCREASED	5.7% 11/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	5.5% 11/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations GAMMA-GLUTAMYLTRANSFERASE INCREASED	6.2% 12/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	5.5% 11/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations HAEMOGLOBIN DECREASED	14.4% 28/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	21.1% 42/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations NEUTROPHIL COUNT DECREASED	5.7% 11/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	6.5% 13/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations PLATELET COUNT DECREASED	9.8% 19/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	9.0% 18/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations WEIGHT DECREASED	26.3% 51/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	13.1% 26/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations WEIGHT INCREASED	11.9% 23/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	7.0% 14/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Investigations WHITE BLOOD CELL COUNT DECREASED	7.2% 14/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	4.5% 9/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Metabolism and nutrition disorders DECREASED APPETITE	38.7% 75/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	30.2% 60/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Metabolism and nutrition disorders HYPERGLYCAEMIA	5.2% 10/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	2.5% 5/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Metabolism and nutrition disorders HYPOALBUMINAEMIA	6.7% 13/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	6.5% 13/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Metabolism and nutrition disorders HYPOCALCAEMIA	11.9% 23/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	7.0% 14/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Metabolism and nutrition disorders HYPONATRAEMIA	8.2% 16/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	9.0% 18/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Metabolism and nutrition disorders HYPOPHOSPHATAEMIA	6.2% 12/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	2.0% 4/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Musculoskeletal and connective tissue disorders BACK PAIN	5.7% 11/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	5.5% 11/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Nervous system disorders HYPOAESTHESIA	12.9% 25/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	13.6% 27/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Nervous system disorders NEUROTOXICITY	7.7% 15/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	9.0% 18/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Psychiatric disorders INSOMNIA	5.2% 10/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	5.0% 10/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Respiratory, thoracic and mediastinal disorders COUGH	9.3% 18/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	8.0% 16/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Skin and subcutaneous tissue disorders DERMATITIS ACNEIFORM	16.0% 31/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.50% 1/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Skin and subcutaneous tissue disorders PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	8.8% 17/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	3.5% 7/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Skin and subcutaneous tissue disorders PRURITUS	5.2% 10/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	1.5% 3/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Skin and subcutaneous tissue disorders RASH	61.9% 120/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	3.5% 7/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Skin and subcutaneous tissue disorders SKIN FISSURES	8.8% 17/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Metabolism and nutrition disorders HYPOKALAEMIA	33.5% 65/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	19.1% 38/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Metabolism and nutrition disorders HYPOMAGNESAEMIA	20.1% 39/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	3.0% 6/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
General disorders ASTHENIA	5.7% 11/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	6.5% 13/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Metabolism and nutrition disorders HYPOPROTEINAEMIA	3.6% 7/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	5.5% 11/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.
Skin and subcutaneous tissue disorders DRY SKIN	5.7% 11/194 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.	0.00% 0/199 • Baseline up to Safety Follow up (assessed up to 333 weeks) Modified safety population included all subjects with RAS wild type tumor status who received any study treatment (cetuximab, oxaliplatin or 5-FU/FA). Subjects were analyzed as treated.

Additional Information

Communication Center

Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: service@emdgroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER