Comparison of Treatment Effect of Chemotherapy With Panitumumab to Chemotherapy Alone

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00339183
• Collaborator: (none)
• Enrollment: 1,186
• Arms: 2
• Actual Duration (Months): 52.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the treatment effect of panitumumab plus FOLFIRI compared to FOLFIRI alone as second line therapy for metastatic colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: Panitumumab; Drug: FOLFIRI	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1186 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter Phase 3 Study to Compare the Efficacy of Panitumumab in Combination With Chemotherapy to the Efficacy of Chemotherapy Alone in Patients With Previously Treated Metastatic Colorectal Cancer
• Actual Study Start Date: Jun 30, 2006
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panitumumab Plus FOLFIRI Participants received panitumumab as an intravenous (IV) infusion at a dose of 6 mg/kg plus a standard chemotherapy regimen (FOLFIRI) consisting of 5-fluorouracil (5-FU), leucovorin and irinotecan. Treatment was administered in cycles every two weeks.	Drug: Panitumumab; Panitumumab was administered by IV infusion on Day 1 of each 14-day cycle, just before administration of FOLFIRI chemotherapy.; Other Names: Vectibix® ; Drug: FOLFIRI; FOLFIRI chemotherapy was initiated on Day 1 of each treatment cycle at the following starting doses: irinotecan 180 mg/m^2, leucovorin 400 mg/m^2 racemate (or 200 mg/m^2 I-leucovorin), 5-FU bolus 400 mg/m^2, 5-FU infusion 2400 mg/m^2.
Active Comparator: FOLFIRI Alone Participants received standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment is administered in cycles every two weeks.	Drug: FOLFIRI; FOLFIRI chemotherapy was initiated on Day 1 of each treatment cycle at the following starting doses: irinotecan 180 mg/m^2, leucovorin 400 mg/m^2 racemate (or 200 mg/m^2 I-leucovorin), 5-FU bolus 400 mg/m^2, 5-FU infusion 2400 mg/m^2.

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [From randomization until the data cut-off date of 8 April 2008. Maximum follow-up time was 17 months.]

   Progression-free survival was defined as the time from randomization to first disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria or death, based on independent central radiological assessment. Participants who were alive but did not meet criteria for progression by the data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.

2. Overall Survival [From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months]

   Overall survival was defined as the time from randomization to the date of death. Participants who had not died by the analysis data cutoff date had their time of death censored at their last contact date.

Secondary Outcome Measures

1. Percentage of Participants With an Objective Response [Every 8 weeks until disease progression up to the data cut-off date of 30 April 2009. Maximum time on follow-up was 33 months.]

   Participants were evaluated for tumor response per the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 8 weeks until disease progression. Objective response was defined as the incidence of either a confirmed complete or partial response (CR or PR) while on study, as determined by blinded independent central review and confirmed no less than 4-weeks after the criteria for response are first met. CR: Disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions and no progression of non-target or no new lesions, or, disappearance of all target lesions and the persistence of ≥ 1 non-target lesion not qualifying for either CR or progressive disease. Participants without a post-baseline assessment were considered non-responders.

2. Time to Disease Progression [From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months]

   Time to progression was defined as the time from the randomization date to the date of first observed disease progression per the modified RECIST criteria. Participants not meeting these criteria by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.

3. Duration of Response [From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months]

   Calculated only for those participants with an objective response as the time from the first objective response (subsequently confirmed within no less than 4 weeks) to first observed disease progression per modified-RECIST criteria. Participants not meeting these criteria by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.

4. Number of Participants With Adverse Events (AEs) [From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months.]

   A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the subject at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The relationship of the adverse event to the study treatment was assessed by the Investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the study treatment?"

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Man or woman at least 18 years old

• Diagnosis of metastatic colorectal cancer (mCRC)

• One and only one chemotherapy regimen for mCRC consisting of first-line 5-FU -based chemotherapy

• Radiologically documented disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria during treatment or within 6 months of last dose of first-line chemotherapy

• At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST

• Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2

• Paraffin-embedded tumor tissue from the primary tumor or metastasis available for central analyses

• Adequate hematologic, renal, and hepatic functions

• Negative pregnancy test within 72 hours of enrollment

• Other protocol-specified criteria may apply

Exclusion Criteria:

• History of or known presence of central nervous system (CNS) metastases

• History of another primary cancer within 5 years of randomization

• Prior irinotecan therapy

• Prior anti-epidermal growth factor receptor (EGFr) antibody therapy or treatment with small molecule EGFr inhibitors

• Any investigational agent or therapy within 30 days before randomization

• Known allergy or hypersensitivity to irinotecan, 5-FU or leucovorin

• History of interstitial lung disease or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan

• Active inflammatory bowel disease or other bowel disease causing chronic diarrhea

• Known positive tests for human immunodefiency virus (HIV), hepatitis C viris (HCV), acute or chronic active hepatitis B virus (HBV)

• Major surgery within 28 days of randomization or minor surgical procedure within 14 days of randomization

• Pregnant or breast-feeding

• Man or woman of child-bearing potential not consenting to use adequate contraceptive methods or abstinence during the course of the study and for 6 months after last study drug administration (women) or 1 month after last study drug administration (men)

• Other protocol-specified criteria may apply

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• Author and team decided to wait for CALGB RAS data presented Sept 29 at ESMO.
• Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tian Y, Sidhu R. Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jan;25(1):107-16. doi: 10.1093/annonc/mdt523. Erratum in: Ann Oncol. 2014 Mar;25(3):757. Ann Oncol. 2014 Mar;25(3):757.
• Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. doi: 10.1200/JCO.2009.27.6055. Epub 2010 Oct 4.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00339183
• Other Study ID Numbers: 20050181
• First Posted: Jun 20, 2006
• Last Update Posted: Aug 31, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by Amgen: Oncology; Cancer; Metastatic Colorectal Cancer; EGFr; Panitumumab; Clinical Trial; Amgen
• Additional relevant MeSH terms: Colorectal Neoplasms; Panitumumab

Study Results

Participant Flow

Recruitment Details	First patient enrolled 30 June 2006; Last patient enrolled 13 March 2008.

Arm/Group Title	Panitumumab Plus FOLFIRI	FOLFIRI Alone
Arm/Group Description	Participants were randomized to 6 mg/kg panitumumab intravenous infusion plus a standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment was administered in cycles every two weeks.	Participants were randomized to receive a standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment was administered in cycles every two weeks.
Period Title: Overall Study
STARTED	591	595
Received Study Drug	588	593
COMPLETED	470	490
NOT COMPLETED	121	105

Baseline Characteristics

Arm/Group Title	Panitumumab Plus FOLFIRI	FOLFIRI Alone	Total
Arm/Group Description	Participants were randomized to 6 mg/kg panitumumab intravenous infusion plus a standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment was administered in cycles every two weeks.	Participants were randomized to receive a standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment was administered in cycles every two weeks.	Total of all reporting groups
Overall Participants	591	595	1186
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (10.5)	60.9 (10.6)	60.6 (10.5)
Sex: Female, Male (Count of Participants)
Female	245 41.5%	219 36.8%	464 39.1%
Male	346 58.5%	376 63.2%	722 60.9%
Race/Ethnicity, Customized (participants) [Number]
White or Caucasian	568 96.1%	569 95.6%	1137 95.9%
Black or African American	4 0.7%	5 0.8%	9 0.8%
Hispanic or Latino	2 0.3%	3 0.5%	5 0.4%
Asian	2 0.3%	3 0.5%	5 0.4%
Japanese	9 1.5%	11 1.8%	20 1.7%
Native Hawaiian or Other Pacific Islander	1 0.2%	1 0.2%	2 0.2%
Aborigine	2 0.3%	1 0.2%	3 0.3%
Other	3 0.5%	2 0.3%	5 0.4%
KRAS Status (participants) [Number]
Wild-type KRAS	303 51.3%	294 49.4%	597 50.3%
Mutant KRAS	238 40.3%	248 41.7%	486 41%
Unevaluable KRAS	50 8.5%	53 8.9%	103 8.7%
Prior Oxaliplatin Exposure for mCRC (participants) [Number]
No	179 30.3%	182 30.6%	361 30.4%
Yes	412 69.7%	413 69.4%	825 69.6%
Prior Bevacizumab Exposure for mCRC (participants) [Number]
No	480 81.2%	483 81.2%	963 81.2%
Yes	111 18.8%	112 18.8%	223 18.8%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
Grade 0 or 1	564 95.4%	565 95%	1129 95.2%
Grade 2	27 4.6%	30 5%	57 4.8%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	Progression-free survival was defined as the time from randomization to first disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria or death, based on independent central radiological assessment. Participants who were alive but did not meet criteria for progression by the data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.
Time Frame	From randomization until the data cut-off date of 8 April 2008. Maximum follow-up time was 17 months.

Outcome Measure Data

Analysis Population Description

KRAS Efficacy Analysis Set (participants for whom KRAS status was assessed)

Arm/Group Title	Wild-type KRAS - Panitumumab Plus FOLFIRI	Wild-type KRAS - FOLFIRI Alone	Mutant KRAS - Panitumumab Plus FOLFIRI	Mutant KRAS - FOLFIRI Alone
Arm/Group Description	Participants with wild-type KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with wild-type KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with mutant KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with mutant KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.
Measure Participants	303	294	238	248
Median (95% Confidence Interval) [months]	5.9	3.9	5.0	4.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Wild-type KRAS - Panitumumab Plus FOLFIRI, Wild-type KRAS - FOLFIRI Alone
	Comments	An overall 5% significance level was used to compare treatments with respect to both overall survival (OS) and PFS. A 4% and 1% level (2-sided) was used to independently test OS and PFS, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments
	Method	Stratified log-rank test
	Comments	P-value based on a 2-sided log-rank test stratified by ECOG (0 or 1 vs. 2), prior bevacizumab exposure, and prior oxaliplatin exposure (yes or no).
Method of Estimation	Estimation Parameter	Normal score
	Estimated Value	-2.91
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	A normal score <0 indicates fewer than expected events for the Panitumumab plus FOLFIRI arm and therefore a longer progression-free survival time.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mutant KRAS - Panitumumab Plus FOLFIRI, Mutant KRAS - FOLFIRI Alone
	Comments	PFS in the Mutant Efficacy Analysis Set was compared at a 1% level conditional upon first demonstrating a significant difference in PFS in the Wild-type KRAS Efficacy Analysis Set.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1448
	Comments
	Method	Stratified log-rank test
	Comments	P-value based on a 2-sided log-rank test stratified by ECOG (0 or 1 vs. 2), prior bevacizumab exposure and prior oxaliplatin exposure (yes or no).
Method of Estimation	Estimation Parameter	Normal score
	Estimated Value	-1.46
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	A normal score <0 indicates fewer than expected events for the Panitumumab plus FOLFIRI arm and therefore a longer progression-free survival time.

2. Primary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from randomization to the date of death. Participants who had not died by the analysis data cutoff date had their time of death censored at their last contact date.
Time Frame	From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months

Outcome Measure Data

Analysis Population Description

KRAS Efficacy Analysis Set

Arm/Group Title	Wild-type KRAS - Panitumumab Plus FOLFIRI	Wild-type KRAS - FOLFIRI Alone	Mutant KRAS - Panitumumab Plus FOLFIRI	Mutant KRAS - FOLFIRI Alone
Arm/Group Description	Participants with wild-type KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with wild-type KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with mutant KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with mutant KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.
Measure Participants	303	294	238	248
Median (95% Confidence Interval) [months]	14.5	12.5	11.8	11.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Wild-type KRAS - Panitumumab Plus FOLFIRI, Wild-type KRAS - FOLFIRI Alone
	Comments	An overall 5% significance level was used to compare treatments with respect to both overall survival (OS) and PFS. A 4% and 1% level (2-sided) was used to independently test OS and PFS, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1154
	Comments
	Method	Stratified log-rank test
	Comments	P-value based on a 2-sided log-rank test stratified by ECOG (0 or 1 vs. 2), prior bevacizumab exposure, and prior oxaliplatin exposure (yes or no).
Method of Estimation	Estimation Parameter	Normal score
	Estimated Value	-1.57
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	A normal score <0 indicates fewer than expected events for the Panitumumab plus FOLFIRI arm and therefore a longer overall survival time.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mutant KRAS - Panitumumab Plus FOLFIRI, Mutant KRAS - FOLFIRI Alone
	Comments	The treatment effect on OS in the Mutant KRAS Efficacy Analysis Set was compared at the 4% level conditional on first demonstrating a significant OS treatment effect in the Wild-type KRAS Efficacy Analysis Set.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5503
	Comments
	Method	Stratified log-rank test
	Comments	P-value based on a 2-sided log-rank test stratified by ECOG (0 or 1 vs. 2), prior bevacizumab exposure, and prior oxaliplatin exposure (yes or no).
Method of Estimation	Estimation Parameter	Normal score
	Estimated Value	-0.60
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	A normal score <0 indicates fewer than expected events for the Panitumumab plus FOLFIRI arm and therefore a longer overall survival time.

3. Secondary Outcome

Title	Percentage of Participants With an Objective Response
Description	Participants were evaluated for tumor response per the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 8 weeks until disease progression. Objective response was defined as the incidence of either a confirmed complete or partial response (CR or PR) while on study, as determined by blinded independent central review and confirmed no less than 4-weeks after the criteria for response are first met. CR: Disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions and no progression of non-target or no new lesions, or, disappearance of all target lesions and the persistence of ≥ 1 non-target lesion not qualifying for either CR or progressive disease. Participants without a post-baseline assessment were considered non-responders.
Time Frame	Every 8 weeks until disease progression up to the data cut-off date of 30 April 2009. Maximum time on follow-up was 33 months.

Outcome Measure Data

Analysis Population Description

KRAS Central Tumor Response Analysis Set: subset of participants with at least one uni-dimensionally measurable lesion per the modified RECIST criteria per blinded central radiology review for whom KRAS was assessed.

Arm/Group Title	Wild-type KRAS - Panitumumab Plus FOLFIRI	Wild-type KRAS - FOLFIRI Alone	Mutant KRAS - Panitumumab Plus FOLFIRI	Mutant KRAS - FOLFIRI Alone
Arm/Group Description	Participants with wild-type KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with wild-type KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with mutant KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with mutant KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.
Measure Participants	297	285	232	237
Number (95% Confidence Interval) [percentage of participants]	35.35 6%	9.82 1.7%	13.36 1.1%	13.92 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Wild-type KRAS - Panitumumab Plus FOLFIRI, Wild-type KRAS - FOLFIRI Alone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Stratified exact test
	Comments	Adjusted for ECOG score, prior bevacizumab exposure, prior oxaliplatin exposure.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.33
	Confidence Interval	(2-Sided) 95%; 3.21 to 8.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio is defined as the odds of having an objective response in the panitumumab plus arm relative to the odds on the FOLFIRI alone arm.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mutant KRAS - Panitumumab Plus FOLFIRI, Mutant KRAS - FOLFIRI Alone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Stratified exact test
	Comments	Adjusted for ECOG score, prior bevacizumab exposure, prior oxaliplatin exposure.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.56 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio is defined as the odds of having an objective response in the panitumumab plus arm relative to the odds on the FOLFIRI alone arm.

4. Secondary Outcome

Title	Time to Disease Progression
Description	Time to progression was defined as the time from the randomization date to the date of first observed disease progression per the modified RECIST criteria. Participants not meeting these criteria by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.
Time Frame	From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months

Outcome Measure Data

Analysis Population Description

KRAS Efficacy Analysis Set

Arm/Group Title	Wild-type KRAS - Panitumumab Plus FOLFIRI	Wild-type KRAS - FOLFIRI Alone	Mutant KRAS - Panitumumab Plus FOLFIRI	Mutant KRAS - FOLFIRI Alone
Arm/Group Description	Participants with wild-type KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with wild-type KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with mutant KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with mutant KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.
Measure Participants	303	294	238	248
Median (95% Confidence Interval) [months]	7.3	5.3	5.5	5.5

5. Secondary Outcome

Title	Duration of Response
Description	Calculated only for those participants with an objective response as the time from the first objective response (subsequently confirmed within no less than 4 weeks) to first observed disease progression per modified-RECIST criteria. Participants not meeting these criteria by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.
Time Frame	From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months

Outcome Measure Data

Analysis Population Description

KRAS Central Tumor Response Analysis Set: Responders

Arm/Group Title	Wild-type KRAS - Panitumumab Plus FOLFIRI	Wild-type KRAS - FOLFIRI Alone	Mutant KRAS - Panitumumab Plus FOLFIRI	Mutant KRAS - FOLFIRI Alone
Arm/Group Description	Participants with wild-type KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with wild-type KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with mutant KRAS were randomized to 6 mg/kg panitumumab plus FOLFIRI chemotherapy regimen administered in cycles every two weeks.	Participants with mutant KRAS were randomized to FOLFIRI chemotherapy regimen administered in cycles every two weeks.
Measure Participants	105	28	31	33
Median (95% Confidence Interval) [months]	7.6	6.6	6.0	7.4

6. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	A serious adverse event (SAE) is defined by regulatory authorities as one that • is fatal • is life threatening (places the subject at immediate risk of death) • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The relationship of the adverse event to the study treatment was assessed by the Investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the study treatment?"
Time Frame	From randomization until the data cut-off date of 30 April 2009. Maximum follow-up time was 33 months.

Outcome Measure Data

Analysis Population Description

Safety analysis set: all participants who received at least 1 dose of panitumumab or chemotherapy. One participant was randomized to Panitumumab Plus FOLFIRI, but received FOLFIRI Alone and is included in the FOLFIRI Alone group for safety analyses.

Arm/Group Title	Panitumumab Plus FOLFIRI	FOLFIRI Alone
Arm/Group Description	Participants received 6 mg/kg panitumumab IV plus a standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment was administered in cycles every two weeks.	Participants received FOLFIRI chemotherapy regimen administered in cycles every two weeks.
Measure Participants	587	594
Any adverse event	584 98.8%	573 96.3%
Serious adverse event	232 39.3%	175 29.4%
Leading to discontinuation of any study drug	123 20.8%	64 10.8%
Treatment-related adverse event (TRAE)	577 97.6%	542 91.1%
Serious treatment-related adverse event	124 21%	90 15.1%
TRAE leading to discontinuation of any study drug	97 16.4%	34 5.7%

Adverse Events

Time Frame	The median treatment period was approximately 6.2 months in the Panitumumab plus FOLFIRI arm, and 4.7 months in the FOLFIRI Alone arm.
Adverse Event Reporting Description	One participant was randomized to Panitumumab Plus FOLFIRI, but received FOLFIRI Alone and is included in the FOLFIRI Alone group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Panitumumab Plus FOLFIRI		FOLFIRI Alone
Arm/Group Description	Participants received 6 mg/kg panitumumab IV plus a standard chemotherapy regimen (FOLFIRI) consisting of 5-FU, leucovorin and irinotecan. Treatment was administered in cycles every two weeks.		Participants received FOLFIRI chemotherapy regimen administered in cycles every two weeks.
All Cause Mortality
	Panitumumab Plus FOLFIRI		FOLFIRI Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Panitumumab Plus FOLFIRI		FOLFIRI Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	232/587 (39.5%)		175/594 (29.5%)
Blood and lymphatic system disorders
Anaemia	5/587 (0.9%)		5/594 (0.8%)
Disseminated intravascular coagulation	1/587 (0.2%)		0/594 (0%)
Febrile bone marrow aplasia	2/587 (0.3%)		0/594 (0%)
Febrile neutropenia	11/587 (1.9%)		16/594 (2.7%)
Leukopenia	4/587 (0.7%)		0/594 (0%)
Neutropenia	6/587 (1%)		12/594 (2%)
Pancytopenia	1/587 (0.2%)		0/594 (0%)
Cardiac disorders
Acute myocardial infarction	1/587 (0.2%)		0/594 (0%)
Angina pectoris	1/587 (0.2%)		0/594 (0%)
Arrhythmia	1/587 (0.2%)		0/594 (0%)
Arteriospasm coronary	1/587 (0.2%)		1/594 (0.2%)
Bradycardia	0/587 (0%)		1/594 (0.2%)
Cardiac arrest	0/587 (0%)		1/594 (0.2%)
Cardiac failure	0/587 (0%)		1/594 (0.2%)
Cardiac failure acute	1/587 (0.2%)		1/594 (0.2%)
Cardio-respiratory arrest	1/587 (0.2%)		0/594 (0%)
Cardiopulmonary failure	1/587 (0.2%)		0/594 (0%)
Myocardial infarction	1/587 (0.2%)		1/594 (0.2%)
Palpitations	1/587 (0.2%)		0/594 (0%)
Sinus bradycardia	1/587 (0.2%)		0/594 (0%)
Sinus tachycardia	1/587 (0.2%)		0/594 (0%)
Tachycardia	0/587 (0%)		2/594 (0.3%)
Congenital, familial and genetic disorders
Aplasia	2/587 (0.3%)		1/594 (0.2%)
Ear and labyrinth disorders
Vertigo	0/587 (0%)		1/594 (0.2%)
Eye disorders
Diplopia	0/587 (0%)		1/594 (0.2%)
Gastrointestinal disorders
Abdominal discomfort	0/587 (0%)		1/594 (0.2%)
Abdominal hernia	0/587 (0%)		1/594 (0.2%)
Abdominal pain	12/587 (2%)		13/594 (2.2%)
Abdominal pain lower	1/587 (0.2%)		1/594 (0.2%)
Abdominal pain upper	2/587 (0.3%)		1/594 (0.2%)
Anal fistula	1/587 (0.2%)		1/594 (0.2%)
Anal haemorrhage	1/587 (0.2%)		0/594 (0%)
Anal ulcer	1/587 (0.2%)		0/594 (0%)
Anorectal disorder	1/587 (0.2%)		0/594 (0%)
Ascites	0/587 (0%)		3/594 (0.5%)
Colitis	1/587 (0.2%)		1/594 (0.2%)
Colonic obstruction	2/587 (0.3%)		4/594 (0.7%)
Colonic stenosis	0/587 (0%)		1/594 (0.2%)
Constipation	2/587 (0.3%)		3/594 (0.5%)
Diarrhoea	33/587 (5.6%)		23/594 (3.9%)
Duodenal obstruction	1/587 (0.2%)		0/594 (0%)
Dyspepsia	1/587 (0.2%)		1/594 (0.2%)
Dysphagia	0/587 (0%)		1/594 (0.2%)
Enterocolitis haemorrhagic	1/587 (0.2%)		0/594 (0%)
Faecal vomiting	0/587 (0%)		1/594 (0.2%)
Flatulence	1/587 (0.2%)		0/594 (0%)
Gastric haemorrhage	0/587 (0%)		1/594 (0.2%)
Gastritis haemorrhagic	1/587 (0.2%)		0/594 (0%)
Gastrointestinal obstruction	0/587 (0%)		2/594 (0.3%)
Gastrointestinal toxicity	1/587 (0.2%)		0/594 (0%)
Haematemesis	0/587 (0%)		1/594 (0.2%)
Haematochezia	0/587 (0%)		1/594 (0.2%)
Ileal perforation	0/587 (0%)		1/594 (0.2%)
Ileus	4/587 (0.7%)		4/594 (0.7%)
Intestinal obstruction	9/587 (1.5%)		9/594 (1.5%)
Intestinal perforation	1/587 (0.2%)		0/594 (0%)
Nausea	12/587 (2%)		5/594 (0.8%)
Neutropenic colitis	0/587 (0%)		1/594 (0.2%)
Oesophagitis ulcerative	0/587 (0%)		1/594 (0.2%)
Pancreatitis	1/587 (0.2%)		1/594 (0.2%)
Proctalgia	1/587 (0.2%)		1/594 (0.2%)
Proctitis	0/587 (0%)		1/594 (0.2%)
Rectal haemorrhage	3/587 (0.5%)		1/594 (0.2%)
Reflux oesophagitis	1/587 (0.2%)		0/594 (0%)
Retroperitoneal haemorrhage	1/587 (0.2%)		0/594 (0%)
Sigmoiditis	0/587 (0%)		1/594 (0.2%)
Small intestinal obstruction	6/587 (1%)		4/594 (0.7%)
Stomatitis	1/587 (0.2%)		3/594 (0.5%)
Subileus	2/587 (0.3%)		4/594 (0.7%)
Umbilical hernia	0/587 (0%)		1/594 (0.2%)
Volvulus	1/587 (0.2%)		0/594 (0%)
Vomiting	17/587 (2.9%)		13/594 (2.2%)
General disorders
Accidental death	1/587 (0.2%)		0/594 (0%)
Asthenia	8/587 (1.4%)		1/594 (0.2%)
Catheter related complication	2/587 (0.3%)		0/594 (0%)
Catheter site related reaction	1/587 (0.2%)		0/594 (0%)
Catheter thrombosis	1/587 (0.2%)		1/594 (0.2%)
Chest discomfort	0/587 (0%)		1/594 (0.2%)
Chest pain	3/587 (0.5%)		3/594 (0.5%)
Chills	1/587 (0.2%)		2/594 (0.3%)
Death	1/587 (0.2%)		0/594 (0%)
Fatigue	5/587 (0.9%)		5/594 (0.8%)
Gait disturbance	0/587 (0%)		1/594 (0.2%)
General physical health deterioration	6/587 (1%)		8/594 (1.3%)
Generalised oedema	1/587 (0.2%)		0/594 (0%)
Hyperthermia	2/587 (0.3%)		0/594 (0%)
Malaise	1/587 (0.2%)		2/594 (0.3%)
Mucosal inflammation	2/587 (0.3%)		4/594 (0.7%)
Multi-organ failure	1/587 (0.2%)		0/594 (0%)
Oedema peripheral	0/587 (0%)		1/594 (0.2%)
Pain	7/587 (1.2%)		1/594 (0.2%)
Performance status decreased	4/587 (0.7%)		0/594 (0%)
Pyrexia	24/587 (4.1%)		16/594 (2.7%)
Sudden death	2/587 (0.3%)		1/594 (0.2%)
Hepatobiliary disorders
Bile duct obstruction	1/587 (0.2%)		1/594 (0.2%)
Biliary colic	1/587 (0.2%)		0/594 (0%)
Biliary dilatation	1/587 (0.2%)		0/594 (0%)
Cholangiolitis	1/587 (0.2%)		0/594 (0%)
Cholangitis	1/587 (0.2%)		3/594 (0.5%)
Cholestasis	2/587 (0.3%)		1/594 (0.2%)
Hepatic failure	0/587 (0%)		1/594 (0.2%)
Hyperbilirubinaemia	2/587 (0.3%)		0/594 (0%)
Jaundice	1/587 (0.2%)		1/594 (0.2%)
Jaundice cholestatic	1/587 (0.2%)		0/594 (0%)
Portal vein thrombosis	1/587 (0.2%)		0/594 (0%)
Immune system disorders
Anaphylactic reaction	1/587 (0.2%)		0/594 (0%)
Drug hypersensitivity	0/587 (0%)		1/594 (0.2%)
Infections and infestations
Abdominal abscess	1/587 (0.2%)		2/594 (0.3%)
Abdominal infection	1/587 (0.2%)		0/594 (0%)
Abscess	0/587 (0%)		1/594 (0.2%)
Actinomycotic pulmonary infection	0/587 (0%)		1/594 (0.2%)
Bacteraemia	2/587 (0.3%)		1/594 (0.2%)
Biliary sepsis	0/587 (0%)		1/594 (0.2%)
Bronchitis	1/587 (0.2%)		1/594 (0.2%)
Campylobacter infection	1/587 (0.2%)		0/594 (0%)
Candida sepsis	1/587 (0.2%)		0/594 (0%)
Candidiasis	0/587 (0%)		1/594 (0.2%)
Catheter related infection	7/587 (1.2%)		3/594 (0.5%)
Catheter sepsis	1/587 (0.2%)		0/594 (0%)
Catheter site infection	1/587 (0.2%)		0/594 (0%)
Cellulitis	6/587 (1%)		1/594 (0.2%)
Device related infection	1/587 (0.2%)		0/594 (0%)
Escherichia sepsis	0/587 (0%)		1/594 (0.2%)
Febrile infection	0/587 (0%)		1/594 (0.2%)
Gastroenteritis	0/587 (0%)		1/594 (0.2%)
Gastroenteritis viral	1/587 (0.2%)		0/594 (0%)
Infection	3/587 (0.5%)		1/594 (0.2%)
Influenza	1/587 (0.2%)		0/594 (0%)
Klebsiella infection	0/587 (0%)		1/594 (0.2%)
Lower respiratory tract infection	0/587 (0%)		1/594 (0.2%)
Neutropenic sepsis	1/587 (0.2%)		1/594 (0.2%)
Oropharyngitis fungal	1/587 (0.2%)		0/594 (0%)
Pneumonia	4/587 (0.7%)		4/594 (0.7%)
Post procedural infection	1/587 (0.2%)		0/594 (0%)
Pyelonephritis	1/587 (0.2%)		1/594 (0.2%)
Pyelonephritis acute	1/587 (0.2%)		0/594 (0%)
Respiratory tract infection	1/587 (0.2%)		2/594 (0.3%)
Sepsis	4/587 (0.7%)		3/594 (0.5%)
Septic shock	1/587 (0.2%)		2/594 (0.3%)
Staphylococcal infection	0/587 (0%)		1/594 (0.2%)
Staphylococcal sepsis	2/587 (0.3%)		0/594 (0%)
Subcutaneous abscess	3/587 (0.5%)		1/594 (0.2%)
Upper respiratory tract infection	0/587 (0%)		1/594 (0.2%)
Urinary tract infection	5/587 (0.9%)		3/594 (0.5%)
Urosepsis	2/587 (0.3%)		1/594 (0.2%)
Vaginitis bacterial	1/587 (0.2%)		0/594 (0%)
Viral infection	1/587 (0.2%)		0/594 (0%)
Wound infection	1/587 (0.2%)		0/594 (0%)
Injury, poisoning and procedural complications
Concussion	1/587 (0.2%)		0/594 (0%)
Contrast media reaction	0/587 (0%)		1/594 (0.2%)
Drug administration error	1/587 (0.2%)		0/594 (0%)
Femur fracture	1/587 (0.2%)		1/594 (0.2%)
Gastrointestinal stoma complication	0/587 (0%)		1/594 (0.2%)
Incisional hernia	0/587 (0%)		1/594 (0.2%)
Joint injury	0/587 (0%)		1/594 (0.2%)
Overdose	1/587 (0.2%)		0/594 (0%)
Perinephric collection	1/587 (0.2%)		0/594 (0%)
Post procedural complication	1/587 (0.2%)		0/594 (0%)
Post procedural haemorrhage	0/587 (0%)		1/594 (0.2%)
Postoperative respiratory distress	0/587 (0%)		1/594 (0.2%)
Procedural site reaction	1/587 (0.2%)		0/594 (0%)
Subdural haematoma	0/587 (0%)		1/594 (0.2%)
Subdural haemorrhage	0/587 (0%)		1/594 (0.2%)
Investigations
Alanine aminotransferase increased	1/587 (0.2%)		0/594 (0%)
Aspartate aminotransferase increased	1/587 (0.2%)		0/594 (0%)
Blood creatinine increased	0/587 (0%)		1/594 (0.2%)
General physical condition abnormal	0/587 (0%)		1/594 (0.2%)
Haemoglobin decreased	2/587 (0.3%)		0/594 (0%)
Weight decreased	1/587 (0.2%)		0/594 (0%)
White blood cell count decreased	0/587 (0%)		1/594 (0.2%)
Metabolism and nutrition disorders
Anorexia	3/587 (0.5%)		3/594 (0.5%)
Dehydration	20/587 (3.4%)		11/594 (1.9%)
Diabetes mellitus	0/587 (0%)		1/594 (0.2%)
Failure to thrive	1/587 (0.2%)		0/594 (0%)
Hyperglycaemia	2/587 (0.3%)		1/594 (0.2%)
Hyperkalaemia	0/587 (0%)		1/594 (0.2%)
Hypocalcaemia	1/587 (0.2%)		0/594 (0%)
Hypokalaemia	6/587 (1%)		0/594 (0%)
Hypomagnesaemia	4/587 (0.7%)		0/594 (0%)
Hypoproteinaemia	1/587 (0.2%)		0/594 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/587 (0.2%)		2/594 (0.3%)
Back pain	3/587 (0.5%)		6/594 (1%)
Bone pain	1/587 (0.2%)		0/594 (0%)
Flank pain	1/587 (0.2%)		0/594 (0%)
Groin pain	1/587 (0.2%)		0/594 (0%)
Hip swelling	1/587 (0.2%)		0/594 (0%)
Muscle atrophy	1/587 (0.2%)		0/594 (0%)
Muscular weakness	1/587 (0.2%)		0/594 (0%)
Musculoskeletal pain	1/587 (0.2%)		0/594 (0%)
Pain in extremity	1/587 (0.2%)		0/594 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bronchial carcinoma	0/587 (0%)		1/594 (0.2%)
Colon cancer metastatic	2/587 (0.3%)		1/594 (0.2%)
Colorectal cancer metastatic	9/587 (1.5%)		10/594 (1.7%)
Gastrointestinal cancer metastatic	1/587 (0.2%)		0/594 (0%)
Malignant ascites	0/587 (0%)		1/594 (0.2%)
Malignant neoplasm progression	1/587 (0.2%)		0/594 (0%)
Malignant peritoneal neoplasm	1/587 (0.2%)		1/594 (0.2%)
Metastases to bone	2/587 (0.3%)		0/594 (0%)
Metastases to central nervous system	3/587 (0.5%)		1/594 (0.2%)
Metastases to liver	1/587 (0.2%)		0/594 (0%)
Metastatic neoplasm	1/587 (0.2%)		0/594 (0%)
Tumour associated fever	1/587 (0.2%)		0/594 (0%)
Tumour haemorrhage	0/587 (0%)		1/594 (0.2%)
Tumour local invasion	0/587 (0%)		1/594 (0.2%)
Nervous system disorders
Ataxia	2/587 (0.3%)		0/594 (0%)
Brain oedema	1/587 (0.2%)		0/594 (0%)
Cerebral haemorrhage	1/587 (0.2%)		0/594 (0%)
Cerebral infarction	0/587 (0%)		1/594 (0.2%)
Cerebral ischaemia	1/587 (0.2%)		0/594 (0%)
Cerebrovascular accident	0/587 (0%)		3/594 (0.5%)
Cerebrovascular insufficiency	0/587 (0%)		1/594 (0.2%)
Cholinergic syndrome	1/587 (0.2%)		1/594 (0.2%)
Chorea	1/587 (0.2%)		0/594 (0%)
Coma	1/587 (0.2%)		0/594 (0%)
Depressed level of consciousness	0/587 (0%)		1/594 (0.2%)
Dizziness	0/587 (0%)		1/594 (0.2%)
Epiduritis	1/587 (0.2%)		0/594 (0%)
Epilepsy	1/587 (0.2%)		0/594 (0%)
Headache	1/587 (0.2%)		0/594 (0%)
Hemiplegia	2/587 (0.3%)		0/594 (0%)
Lethargy	1/587 (0.2%)		0/594 (0%)
Loss of consciousness	0/587 (0%)		2/594 (0.3%)
Nervous system disorder	1/587 (0.2%)		0/594 (0%)
Partial seizures	1/587 (0.2%)		0/594 (0%)
Sciatica	1/587 (0.2%)		0/594 (0%)
Spinal cord compression	1/587 (0.2%)		1/594 (0.2%)
Status epilepticus	1/587 (0.2%)		0/594 (0%)
Syncope	2/587 (0.3%)		1/594 (0.2%)
Psychiatric disorders
Anxiety	0/587 (0%)		1/594 (0.2%)
Confusional state	0/587 (0%)		1/594 (0.2%)
Mental status changes	1/587 (0.2%)		1/594 (0.2%)
Mood altered	0/587 (0%)		1/594 (0.2%)
Panic attack	0/587 (0%)		1/594 (0.2%)
Psychotic disorder	0/587 (0%)		1/594 (0.2%)
Renal and urinary disorders
Dysuria	1/587 (0.2%)		0/594 (0%)
Haematuria	1/587 (0.2%)		1/594 (0.2%)
Hydronephrosis	2/587 (0.3%)		0/594 (0%)
Renal colic	2/587 (0.3%)		0/594 (0%)
Renal failure	1/587 (0.2%)		2/594 (0.3%)
Renal failure acute	3/587 (0.5%)		3/594 (0.5%)
Ureteric obstruction	1/587 (0.2%)		1/594 (0.2%)
Urinary retention	1/587 (0.2%)		0/594 (0%)
Urinary tract obstruction	1/587 (0.2%)		0/594 (0%)
Reproductive system and breast disorders
Genital ulceration	1/587 (0.2%)		0/594 (0%)
Pelvic pain	1/587 (0.2%)		0/594 (0%)
Perineal fistula	0/587 (0%)		1/594 (0.2%)
Vulvovaginal pain	1/587 (0.2%)		0/594 (0%)
Respiratory, thoracic and mediastinal disorders
Dysphonia	1/587 (0.2%)		0/594 (0%)
Dyspnoea	4/587 (0.7%)		4/594 (0.7%)
Dyspnoea exertional	1/587 (0.2%)		0/594 (0%)
Haemoptysis	0/587 (0%)		2/594 (0.3%)
Hypoxia	1/587 (0.2%)		0/594 (0%)
Interstitial lung disease	1/587 (0.2%)		0/594 (0%)
Lung disorder	0/587 (0%)		1/594 (0.2%)
Lung infiltration	0/587 (0%)		1/594 (0.2%)
Pleural effusion	3/587 (0.5%)		0/594 (0%)
Pneumonitis	1/587 (0.2%)		0/594 (0%)
Pneumothorax	1/587 (0.2%)		1/594 (0.2%)
Productive cough	0/587 (0%)		1/594 (0.2%)
Pulmonary embolism	17/587 (2.9%)		10/594 (1.7%)
Respiratory distress	0/587 (0%)		1/594 (0.2%)
Respiratory failure	0/587 (0%)		2/594 (0.3%)
Skin and subcutaneous tissue disorders
Angioedema	1/587 (0.2%)		0/594 (0%)
Dermal cyst	1/587 (0.2%)		0/594 (0%)
Dermatitis acneiform	3/587 (0.5%)		0/594 (0%)
Dermatitis contact	1/587 (0.2%)		0/594 (0%)
Erythema	1/587 (0.2%)		0/594 (0%)
Pruritus	1/587 (0.2%)		0/594 (0%)
Rash	5/587 (0.9%)		0/594 (0%)
Skin exfoliation	1/587 (0.2%)		0/594 (0%)
Skin toxicity	3/587 (0.5%)		0/594 (0%)
Surgical and medical procedures
Liver operation	0/587 (0%)		1/594 (0.2%)
Stent placement	0/587 (0%)		1/594 (0.2%)
Vascular disorders
Aortic aneurysm	0/587 (0%)		1/594 (0.2%)
Deep vein thrombosis	7/587 (1.2%)		2/594 (0.3%)
Embolism	0/587 (0%)		1/594 (0.2%)
Embolism venous	0/587 (0%)		1/594 (0.2%)
Haematoma	0/587 (0%)		1/594 (0.2%)
Hypertension	1/587 (0.2%)		0/594 (0%)
Hypotension	2/587 (0.3%)		0/594 (0%)
Orthostatic hypotension	1/587 (0.2%)		0/594 (0%)
Pelvic venous thrombosis	0/587 (0%)		1/594 (0.2%)
Thrombophlebitis	1/587 (0.2%)		0/594 (0%)
Thrombosis	4/587 (0.7%)		2/594 (0.3%)
Vena cava thrombosis	1/587 (0.2%)		1/594 (0.2%)
Venous thrombosis	1/587 (0.2%)		2/594 (0.3%)
Venous thrombosis limb	2/587 (0.3%)		0/594 (0%)
Other (Not Including Serious) Adverse Events
	Panitumumab Plus FOLFIRI		FOLFIRI Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	575/587 (98%)		546/594 (91.9%)
Blood and lymphatic system disorders
Anaemia	79/587 (13.5%)		110/594 (18.5%)
Leukopenia	64/587 (10.9%)		60/594 (10.1%)
Neutropenia	207/587 (35.3%)		209/594 (35.2%)
Thrombocytopenia	20/587 (3.4%)		39/594 (6.6%)
Eye disorders
Conjunctivitis	81/587 (13.8%)		11/594 (1.9%)
Gastrointestinal disorders
Abdominal pain	122/587 (20.8%)		105/594 (17.7%)
Abdominal pain upper	37/587 (6.3%)		33/594 (5.6%)
Constipation	139/587 (23.7%)		125/594 (21%)
Diarrhoea	372/587 (63.4%)		321/594 (54%)
Dry mouth	30/587 (5.1%)		10/594 (1.7%)
Dyspepsia	40/587 (6.8%)		32/594 (5.4%)
Nausea	276/587 (47%)		269/594 (45.3%)
Stomatitis	131/587 (22.3%)		75/594 (12.6%)
Vomiting	154/587 (26.2%)		162/594 (27.3%)
General disorders
Asthenia	74/587 (12.6%)		81/594 (13.6%)
Fatigue	203/587 (34.6%)		186/594 (31.3%)
Mucosal inflammation	121/587 (20.6%)		68/594 (11.4%)
Oedema peripheral	59/587 (10.1%)		41/594 (6.9%)
Pain	43/587 (7.3%)		29/594 (4.9%)
Pyrexia	105/587 (17.9%)		89/594 (15%)
Infections and infestations
Paronychia	102/587 (17.4%)		3/594 (0.5%)
Investigations
Weight decreased	60/587 (10.2%)		29/594 (4.9%)
Metabolism and nutrition disorders
Anorexia	146/587 (24.9%)		93/594 (15.7%)
Hypocalcaemia	32/587 (5.5%)		9/594 (1.5%)
Hypokalaemia	65/587 (11.1%)		27/594 (4.5%)
Hypomagnesaemia	120/587 (20.4%)		15/594 (2.5%)
Musculoskeletal and connective tissue disorders
Back pain	62/587 (10.6%)		44/594 (7.4%)
Nervous system disorders
Dizziness	36/587 (6.1%)		35/594 (5.9%)
Headache	34/587 (5.8%)		40/594 (6.7%)
Psychiatric disorders
Insomnia	53/587 (9%)		48/594 (8.1%)
Respiratory, thoracic and mediastinal disorders
Cough	42/587 (7.2%)		55/594 (9.3%)
Dyspnoea	54/587 (9.2%)		36/594 (6.1%)
Epistaxis	52/587 (8.9%)		38/594 (6.4%)
Skin and subcutaneous tissue disorders
Acne	80/587 (13.6%)		10/594 (1.7%)
Alopecia	124/587 (21.1%)		136/594 (22.9%)
Dermatitis acneiform	141/587 (24%)		3/594 (0.5%)
Dry skin	129/587 (22%)		23/594 (3.9%)
Erythema	92/587 (15.7%)		16/594 (2.7%)
Nail disorder	43/587 (7.3%)		8/594 (1.3%)
Palmar-plantar erythrodysaesthesia syndrome	54/587 (9.2%)		22/594 (3.7%)
Pruritus	107/587 (18.2%)		18/594 (3%)
Rash	330/587 (56.2%)		38/594 (6.4%)
Skin fissures	94/587 (16%)		3/594 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.