PEAK: Panitumumab Plus mFOLFOX6 vs. Bevacizumab Plus mFOLFOX6 for First Line Treatment of Metastatic Colorectal Cancer (mCRC) Patients With Wild-Type Kirsten Rat Sarcoma-2 Virus (KRAS) Tumors

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00819780
• Collaborator: (none)
• Enrollment: 285
• Locations: 95
• Arms: 2
• Actual Duration (Months): 86.4
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of this study is to estimate the treatment effect on progression-free survival (PFS) of panitumumab relative to bevacizumab in combination with mFOLFOX6 chemotherapy as first-line therapy in patients with tumors expressing wild-type KRAS, unresectable mCRC.

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer; Colorectal Cancer; Rectal Cancer; Metastatic Colorectal Cancer	Drug: Panitumumab; Drug: Bevacizumab; Drug: mFOLFOX6	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 285 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Phase 2 Study to Compare the Efficacy of Panitumumab in Combination With mFOLFOX6 to the Efficacy of Bevacizumab in Combination With mFOLFOX6 in Patients With Previously Untreated, KRAS Wild-Type, Unresectable, Metastatic Colorectal Cancer
• Actual Study Start Date: Apr 24, 2009
• Actual Primary Completion Date: May 30, 2012
• Actual Study Completion Date: Jul 7, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panitumumab Plus mFOLFOX6 Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and modified FOLFOX6 (mFOLFOX6) chemotherapy regimen consisting of oxaliplatin (85 mg/m^2), leucovorin (400 mg/m^2) and 5-fluorouracil (5-FU) (2400 mg/m^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.	Drug: Panitumumab; Panitumumab is a fully human immunoglobulin G (IgG)2 monoclonal antibody antagonist directed against human Epidermal Growth Factor receptor (EGFr).; Other Names: Vectibix ; Drug: mFOLFOX6; mFOLFOX6 regimen is a combination therapy of oxaliplatin (85 mg/m^2) administered as a 2-hour infusion on Day 1; leucovorin (400 mg/m^2) administered as a 2-hour infusion on Day 1; followed by a loading dose of 5-fluorouracil (5-FU; 400 mg/m^2) IV bolus administered over approximately 2 to 4 minutes on Day 1, then 5- FU (2400 mg/m^2) via ambulatory pump administered for a period of 46 to 48 hours.
Active Comparator: Bevacizumab Plus mFOLFOX6 Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 regimen consisting of oxaliplatin (85 mg/m^2), leucovorin (400 mg/m^2), followed by 5-FU (2400 mg/m^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.	Drug: Bevacizumab; Bevacizumab is a humanized monoclonal IgG1 antibody that is directed against Vascular Endothelial Growth Factor (VEGF).; Other Names: Avastin ; Drug: mFOLFOX6; mFOLFOX6 regimen is a combination therapy of oxaliplatin (85 mg/m^2) administered as a 2-hour infusion on Day 1; leucovorin (400 mg/m^2) administered as a 2-hour infusion on Day 1; followed by a loading dose of 5-fluorouracil (5-FU; 400 mg/m^2) IV bolus administered over approximately 2 to 4 minutes on Day 1, then 5- FU (2400 mg/m^2) via ambulatory pump administered for a period of 46 to 48 hours.

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

   PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.

Secondary Outcome Measures

1. Overall Survival [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

   Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date.

2. Percentage of Participants With an Objective Response [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

   Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.

3. Duration of Response [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

   For participants with a confirmed objective response, the time from first confirmed objective response to radiologic disease progression per modified RECIST 1.0 criteria or death. For participants who responded and have not progressed or died, duration of response was censored at their last evaluable disease assessment date.

4. Time to Disease Progression [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

   Time to progression (TTP) is defined as the time from randomization to the date of radiologic disease progression per modified RECIST 1.0 criteria. Participants not meeting criteria for disease progression by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.

5. Time to Initial Objective Response [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

   For participants with a confirmed objective response, the time from randomization to the date of first confirmed objective response. Assessments are based on the investigator's review of scans using a modified-RECIST v1.0. An objective response is defined as a best tumor response of complete or partial response. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met.

6. Resection Rate [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

   The resection rate was defined as the percentage of participants with a surgical procedure that resulted in partial reduction or complete eradication of all metastatic disease.

7. Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS) [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

   PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.

8. Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

   PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.

9. Overall Survival in Participants With Wild-type RAS [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

   Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date.

10. Overall Survival in Participants With Wild-type RAS / BRAF [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

    Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date.

11. Percentage of Participants With an Objective Response for Participants With Wild-type RAS [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

    Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.

12. Percentage of Participants With an Objective Response for Participants With Wild-type RAS / BRAF [From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.]

    Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.

13. Number of Participants With Adverse Events (AEs) [The time frame for adverse event reporting is from the first dose date to 30 days since the last dose date. The median time frame is 8.0 months for Panitumumab Plus mFOLFOX arm and 7.3 months for Bevacizumab Plus mFOLFOX6 arm.]

    Severity was graded using Common Terminology Criteria for Adverse Events (CTCAE) v3.0, with the exception of some dermatology/skin adverse events that were graded using CTCAE v3.0 with modifications. Fatal adverse events are classified as grade 5. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. Treatment-related AEs were those that the investigator considered a reasonable possibility that might have been caused by study drug.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically-confirmed adenocarcinoma of the colon or rectum in patients with unresectable metastatic (M1) disease

• Patients with at least 1 uni-dimensionally measurable lesion of at least 10 mm per modified Response Evaluation Criteria in Solid Tumors (RECIST) guidelines

• Wild-type KRAS tumor status confirmed by an Amgen approved central laboratory or an experienced laboratory (local laboratory) per local regulatory guidelines using a validated test method

• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1

• Men or women 18 years of age or older

• Adequate hematologic, renal, hepatic, metabolic, and coagulation function

Exclusion Criteria:

• History of prior or concurrent central nervous system (CNS) metastases

• Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma

• Clinically significant cardiac disease

• Clinically significant peripheral sensory neuropathy

• Active inflammatory bowel disease

• Recent gastroduodenal ulcer to be active or uncontrolled

• History of interstitial lung disease

• Recent pulmonary embolism, deep vein thrombosis, or other significant venous event

• Pre-existing bleeding diathesis and/or coagulopathy with exception of well-controlled anticoagulation therapy

• Recent major surgical procedure, open biopsy, or significant traumatic injury not yet recovered from prior major surgery.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35205
2	Research Site	Huntsville	Alabama	United States	35805
3	Research Site	Berkeley	California	United States	94704
4	Research Site	Beverly Hills	California	United States	90211
5	Research Site	Burbank	California	United States	91505
6	Research Site	Fountain Valley	California	United States	92708
7	Research Site	La Verne	California	United States	91750
8	Research Site	Orange	California	United States	92868
9	Research Site	Riverside	California	United States	92501
10	Research Site	Roseville	California	United States	95661
11	Research Site	Denver	Colorado	United States	80218
12	Research Site	Stamford	Connecticut	United States	06902
13	Research Site	Waterbury	Connecticut	United States	06708
14	Research Site	Boynton Beach	Florida	United States	33435
15	Research Site	Coral Springs	Florida	United States	33065
16	Research Site	Daytona Beach	Florida	United States	32114
17	Research Site	Hollywood	Florida	United States	33021
18	Research Site	Lake Worth	Florida	United States	33467
19	Research Site	Alpharetta	Georgia	United States	30005
20	Research Site	Augusta	Georgia	United States	30901
21	Research Site	Savannah	Georgia	United States	31405
22	Research Site	Post Falls	Idaho	United States	83854
23	Research Site	Gurnee	Illinois	United States	60031
24	Research Site	Peoria	Illinois	United States	61615
25	Research Site	Indianapolis	Indiana	United States	46237
26	Research Site	Overland Park	Kansas	United States	66210
27	Research Site	Wichita	Kansas	United States	67214
28	Research Site	Danville	Kentucky	United States	40422
29	Research Site	Hazard	Kentucky	United States	41701
30	Research Site	Paducah	Kentucky	United States	42003
31	Research Site	Baltimore	Maryland	United States	21204
32	Research Site	Bethesda	Maryland	United States	20817
33	Research Site	Boston	Massachusetts	United States	02111
34	Research Site	Kalamazoo	Michigan	United States	49048
35	Research Site	Lambertville	Michigan	United States	48144
36	Research Site	Lansing	Michigan	United States	48912
37	Research Site	Mountain Lakes	New Jersey	United States	07046
38	Research Site	Sparta	New Jersey	United States	07871
39	Research Site	Albuquerque	New Mexico	United States	87131
40	Research Site	Buffalo	New York	United States	14215
41	Research Site	East Setauket	New York	United States	11733
42	Research Site	Staten Island	New York	United States	10301
43	Research Site	Huntersville	North Carolina	United States	28078
44	Research Site	Raleigh	North Carolina	United States	27607
45	Research Site	Akron	Ohio	United States	44304
46	Research Site	Columbus	Ohio	United States	43228
47	Research Site	Hershey	Pennsylvania	United States	17033
48	Research Site	Philadelphia	Pennsylvania	United States	19106
49	Research Site	Greenville	South Carolina	United States	29605
50	Research Site	Mount Pleasant	South Carolina	United States	29464
51	Research Site	Memphis	Tennessee	United States	38120
52	Research Site	Austin	Texas	United States	78759
53	Research Site	Corpus Christi	Texas	United States	78463
54	Research Site	Dallas	Texas	United States	75231
55	Research Site	Round Rock	Texas	United States	78665
56	Research Site	Temple	Texas	United States	76508
57	Research Site	Tyler	Texas	United States	75702
58	Research Site	White River Junction	Vermont	United States	05009
59	Research Site	Chesapeake	Virginia	United States	23320
60	Research Site	Newport News	Virginia	United States	23601
61	Research Site	Newport News	Virginia	United States	23606
62	Research Site	Spokane	Washington	United States	99218
63	Research Site	Vancouver	Washington	United States	98684
64	Research Site	Charleroi		Belgium	6000
65	Research Site	Edegem		Belgium	2650
66	Research Site	Libramont		Belgium	6800
67	Research Site	Sint-Niklaas		Belgium	9100
68	Research Site	Calgary	Alberta	Canada	T2N 4N2
69	Research Site	Edmonton	Alberta	Canada	T6G 1Z2
70	Research Site	Vancouver	British Columbia	Canada	V5Z 4E6
71	Research Site	Victoria	British Columbia	Canada	V8R 6V5
72	Research Site	Oshawa	Ontario	Canada	L1G 2B9
73	Research Site	Greenfield Park	Quebec	Canada	J4V 2H1
74	Research Site	Montreal	Quebec	Canada	H2X 3J4
75	Research Site	Quebec		Canada	G1R 2J6
76	Research Site	Berlin		Germany	13125
77	Research Site	Bielefeld		Germany	33611
78	Research Site	Magdeburg		Germany	39104
79	Research Site	München		Germany	81737
80	Research Site	München		Germany	81925
81	Research Site	Passau		Germany	94032
82	Research Site	Regensburg		Germany	93049
83	Research Site	Würzburg		Germany	97070
84	Research Site	Alba (CN)		Italy	12051
85	Research Site	Fano		Italy	61032
86	Research Site	Genova		Italy	16132
87	Research Site	Mantova		Italy	46100
88	Research Site	Udine		Italy	33100
89	Research Site	Varese		Italy	21100
90	Research Site	Málaga	AndalucÃ-a	Spain	29010
91	Research Site	Santander	Cantabria	Spain	39008
92	Research Site	Sabadell	Cataluña	Spain	08208
93	Research Site	Elche	Comunidad	Spain	03203
94	Research Site	A Coruña	Galicia	Spain	15006
95	Research Site	San Sebastián De Los Reyes	Madrid	Spain	28702

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• Boeckx N, Koukakis R, Op de Beeck K, Rolfo C, Van Camp G, Siena S, Tabernero J, Douillard JY, André T, Peeters M. Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies. Ann Oncol. 2017 Aug 1;28(8):1862-1868. doi: 10.1093/annonc/mdx119.
• Heinemann V, Rivera F, O'Neil BH, Stintzing S, Koukakis R, Terwey JH, Douillard JY. A study-level meta-analysis of efficacy data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in patients with RAS wild-type metastatic colorectal cancer. Eur J Cancer. 2016 Nov;67:11-20. doi: 10.1016/j.ejca.2016.07.019. Epub 2016 Sep 1.
• Modest DP, Rivera F, Bachet JB, de Braud F, Pietrantonio F, Koukakis R, Demonty G, Douillard JY. Panitumumab-based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials. Int J Cancer. 2019 Jul 15;145(2):576-585. doi: 10.1002/ijc.32110. Epub 2019 Jan 24.
• Peeters M, Forget F, Karthaus M, Valladares-Ayerbes M, Zaniboni A, Demonty G, Guan X, Rivera F. Exploratory pooled analysis evaluating the effect of sequence of biological therapies on overall survival in patients with RAS wild-type metastatic colorectal carcinoma. ESMO Open. 2018 Feb 24;3(2):e000297. doi: 10.1136/esmoopen-2017-000297. eCollection 2018.
• Rivera F, Karthaus M, Hecht JR, Sevilla I, Forget F, Fasola G, Canon JL, Guan X, Demonty G, Schwartzberg LS. Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis. 2017 Aug;32(8):1179-1190. doi: 10.1007/s00384-017-2800-1. Epub 2017 Apr 19.
• Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Hecht JR, Yu H, Oliner KS, Go WY. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014 Jul 20;32(21):2240-7. doi: 10.1200/JCO.2013.53.2473. Epub 2014 Mar 31.
• Taieb J, Rivera F, Siena S, Karthaus M, Valladares-Ayerbes M, Gallego J, Geissler M, Koukakis R, Demonty G, Peeters M. Exploratory analyses assessing the impact of early tumour shrinkage and depth of response on survival outcomes in patients with RAS wild-type metastatic colorectal cancer receiving treatment in three randomised panitumumab trials. J Cancer Res Clin Oncol. 2018 Feb;144(2):321-335. doi: 10.1007/s00432-017-2534-z. Epub 2017 Oct 28. Erratum in: J Cancer Res Clin Oncol. 2018 Feb 15;:.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00819780
• Other Study ID Numbers: 20070509
• First Posted: Jan 9, 2009
• Last Update Posted: Aug 21, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Amgen: Colon Cancer; Colorectal Cancer; Rectal Cancer; Panitumumab; Vectibix; modified FOLFOX 6; mFOLFOX 6; FOLFOX; Bevacizumab; Avastin; First-Line; metastatic
• Additional relevant MeSH terms: Colorectal Neoplasms; Rectal Neoplasms; Colonic Neoplasms; Bevacizumab; Panitumumab

Study Results

Participant Flow

Recruitment Details	First patient was enrolled on 24 April 2009; last patient was enrolled on 09 December 2011.

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and modified FOLFOX6 (mFOLFOX6) chemotherapy regimen consisting of oxaliplatin (85 mg/m^2), leucovorin (400 mg/m^2) and 5-fluorouracil (5-FU; 2400 mg/m^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 regimen consisting of oxaliplatin (85 mg/m^2), leucovorin (400 mg/m^2), followed by 5-FU (2400 mg/m^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.
Period Title: Overall Study
STARTED	142	143
Received Study Treatment	139	139
COMPLETED	114	122
NOT COMPLETED	28	21

Baseline Characteristics

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6	Total
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Total of all reporting groups
Overall Participants	142	143	285
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (10.4)	60.5 (9.8)	61.0 (10.1)
Sex: Female, Male (Count of Participants)
Female	56 39.4%	47 32.9%	103 36.1%
Male	86 60.6%	96 67.1%	182 63.9%
Race/Ethnicity, Customized (participants) [Number]
White or Caucasian	131 92.3%	127 88.8%	258 90.5%
Black or African American	9 6.3%	6 4.2%	15 5.3%
Hispanic or Latino	2 1.4%	5 3.5%	7 2.5%
Asian	0 0%	4 2.8%	4 1.4%
Japanese	0 0%	1 0.7%	1 0.4%
Prior Adjuvant Oxaliplatin Therapy (participants) [Number]
Yes	14 9.9%	14 9.8%	28 9.8%
No	128 90.1%	129 90.2%	257 90.2%
RAS and BRAF Mutation Status (participants) [Number]
BRAF wild-type	103 72.5%	108 75.5%	211 74%
RAS Wild-type	88 62%	82 57.3%	170 59.6%
RAS/BRAF wild-type	77 54.2%	79 55.2%	156 54.7%
Testing not performed	13 9.2%	18 12.6%	31 10.9%
Sample acceptance failure	8 5.6%	7 4.9%	15 5.3%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) analysis set (all randomized participants)

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	142	143
Median (95% Confidence Interval) [months]	10.9	10.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus mFOLFOX6, Bevacizumab Plus mFOLFOX6
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3531
	Comments
	Method	Stratified Cox proportional hazards
	Comments	The Cox proportional hazard model is stratified by prior adjuvant oxaliplatin therapy
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.871
	Confidence Interval	(2-Sided) 95%; 0.651 to 1.166
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1.0 favors panitumumab

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis set

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	142	143
Median (95% Confidence Interval) [months]	NA	25.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus mFOLFOX6, Bevacizumab Plus mFOLFOX6
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1386
	Comments
	Method	Stratified Cox proportional hazards
	Comments	The Cox proportional hazard model is stratified by prior adjuvant oxaliplatin therapy
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.723
	Confidence Interval	(2-Sided) 95%; 0.470 to 1.111
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1.0 favors panitumumab

3. Secondary Outcome

Title	Percentage of Participants With an Objective Response
Description	Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Evaluable for Local Tumor Response Analysis Set, defined as the subset of participants in the ITT Analysis Set who had at least 1 unidimensionally measurable lesion per modified RECIST 1.0 per the local investigator.

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	142	142
Number (95% Confidence Interval) [percentage of participants]	57.75 40.7%	53.52 37.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus mFOLFOX6, Bevacizumab Plus mFOLFOX6
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5497
	Comments
	Method	Stratified exact test
	Comments	Stratified by prior adjuvant oxaliplatin therapy
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio is defined as the odds of having an objective response in the panitumumab plus mFOLFOX6 arm relative to the odds in the bevacizumab plus mFOLFOX6 arm.

4. Secondary Outcome

Title	Duration of Response
Description	For participants with a confirmed objective response, the time from first confirmed objective response to radiologic disease progression per modified RECIST 1.0 criteria or death. For participants who responded and have not progressed or died, duration of response was censored at their last evaluable disease assessment date.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Evaluable for Local Tumor Response Analysis Set: Responders

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	82	76
Median (95% Confidence Interval) [months]	10.0	9.0

5. Secondary Outcome

Title	Time to Disease Progression
Description	Time to progression (TTP) is defined as the time from randomization to the date of radiologic disease progression per modified RECIST 1.0 criteria. Participants not meeting criteria for disease progression by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis set

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	142	143
Median (95% Confidence Interval) [months]	11.0	11.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus mFOLFOX6, Bevacizumab Plus mFOLFOX6
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3861
	Comments
	Method	Stratified Cox proportional hazards
	Comments	The Cox proportional hazard model is stratified by prior adjuvant oxaliplatin therapy
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.874
	Confidence Interval	(2-Sided) 95%; 0.645 to 1.185
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1.0 favors panitumumab

6. Secondary Outcome

Title	Time to Initial Objective Response
Description	For participants with a confirmed objective response, the time from randomization to the date of first confirmed objective response. Assessments are based on the investigator's review of scans using a modified-RECIST v1.0. An objective response is defined as a best tumor response of complete or partial response. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Evaluable for Local Tumor Response Analysis Set: Responders

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	82	76
Median (Inter-Quartile Range) [months]	1.8	1.9

7. Secondary Outcome

Title	Resection Rate
Description	The resection rate was defined as the percentage of participants with a surgical procedure that resulted in partial reduction or complete eradication of all metastatic disease.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Intent-to-treat analysis set

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	142	143
Number (95% Confidence Interval) [percentage of participants]	12.68 8.9%	11.19 7.8%

8. Secondary Outcome

Title	Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS)
Description	PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Wild-type RAS Efficacy Analysis Set, defined as a subset of Wild-type KRAS Exon 2 Efficacy Analysis Set including all randomized participants with wild-type KRAS exon 2, 3, 4, NRAS exon 2, 3, and 4.

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	88	82
Median (95% Confidence Interval) [months]	13.0	9.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus mFOLFOX6, Bevacizumab Plus mFOLFOX6
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0286
	Comments
	Method	Stratified Cox proportional hazards
	Comments	The Cox proportional hazard model is stratified by prior adjuvant oxaliplatin therapy
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.651
	Confidence Interval	(2-Sided) 95%; 0.444 to 0.956
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1.0 favors panitumumab

9. Secondary Outcome

Title	Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)
Description	PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Wild-type RAS/BRAF Efficacy Analysis Set was defined as a subset of Wild-type KRAS Exon 2 Efficacy Analysis Set with wild-type KRAS exon 2, 3, and 4, NRAS exon 2, 3, 4, and BRAF exon 15.

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	77	79
Median (95% Confidence Interval) [months]	13.1	9.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus mFOLFOX6, Bevacizumab Plus mFOLFOX6
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0083
	Comments
	Method	Stratified Cox proportional hazards
	Comments	The Cox proportional hazard model is stratified by prior adjuvant oxaliplatin therapy
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.579
	Confidence Interval	(2-Sided) 95%; 0.386 to 0.869
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1.0 favors panitumumab

10. Secondary Outcome

Title	Overall Survival in Participants With Wild-type RAS
Description	Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Wild-type RAS Efficacy Analysis Set, defined as a subset of Wild-type KRAS Exon 2 Efficacy Analysis Set including all randomized participants with wild-type KRAS exon 2, 3, 4, NRAS exon 2, 3, and 4.

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	88	82
Median (95% Confidence Interval) [months]	NA	29.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus mFOLFOX6, Bevacizumab Plus mFOLFOX6
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0934
	Comments
	Method	Stratified Cox proportional hazards
	Comments	The Cox proportional hazard model is stratified by prior adjuvant Oxaliplatin therapy
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.606
	Confidence Interval	(2-Sided) 95%; 0.337 to 1.088
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1.0 favors panitumumab

11. Secondary Outcome

Title	Overall Survival in Participants With Wild-type RAS / BRAF
Description	Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Wild-type RAS/BRAF Efficacy Analysis Set was defined as a subset of Wild-type KRAS Exon 2 Efficacy Analysis Set with wild-type KRAS exon 2, 3, and 4, NRAS exon 2, 3, 4, and BRAF exon 15.

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	77	79
Median (95% Confidence Interval) [months]	NA	29.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus mFOLFOX6, Bevacizumab Plus mFOLFOX6
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0235
	Comments
	Method	Stratified Cox proportional hazards
	Comments	The Cox proportional hazard model is stratified by prior adjuvant oxaliplatin therapy
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.465
	Confidence Interval	(2-Sided) 95%; 0.239 to 0.902
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1.0 favors panitumumab

12. Secondary Outcome

Title	Percentage of Participants With an Objective Response for Participants With Wild-type RAS
Description	Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Wild-type RAS Investigator Tumor Response Analysis Set, defined as the subset of participants in the Wild-type RAS Efficacy Analysis Set who had at least 1 unidimensionally measurable lesion per modified RECIST 1.0 per the local investigator.

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	88	81
Number (95% Confidence Interval) [percentage of participants]	63.64 44.8%	60.49 42.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus mFOLFOX6, Bevacizumab Plus mFOLFOX6
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9426
	Comments
	Method	Stratified exact test
	Comments	Stratified by prior exposure to oxaliplatin
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.55 to 2.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio is defined as the odds of having an objective response in the panitumumab plus mFOLFOX6 arm relative to the odds in the bevacizumab plus mFOLFOX6 arm.

13. Secondary Outcome

Title	Percentage of Participants With an Objective Response for Participants With Wild-type RAS / BRAF
Description	Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.
Time Frame	From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Outcome Measure Data

Analysis Population Description

Wild-type RAS/BRAF Investigator Tumor Response Analysis Set, defined as the subset of participants in the Wild-type RAS/BRAF Efficacy Analysis Set who had at least 1 unidimensionally measurable lesion per modified RECIST 1.0 per the local investigator.

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	77	78
Number (95% Confidence Interval) [percentage of participants]	63.64 44.8%	61.54 43%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Panitumumab Plus mFOLFOX6, Bevacizumab Plus mFOLFOX6
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Stratified exact test
	Comments	Stratified by prior exposure to oxaliplatin
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.52 to 2.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds ratio is defined as the odds of having an objective response in the panitumumab plus mFOLFOX6 arm relative to the odds in the bevacizumab plus mFOLFOX6 arm.

14. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	Severity was graded using Common Terminology Criteria for Adverse Events (CTCAE) v3.0, with the exception of some dermatology/skin adverse events that were graded using CTCAE v3.0 with modifications. Fatal adverse events are classified as grade 5. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. Treatment-related AEs were those that the investigator considered a reasonable possibility that might have been caused by study drug.
Time Frame	The time frame for adverse event reporting is from the first dose date to 30 days since the last dose date. The median time frame is 8.0 months for Panitumumab Plus mFOLFOX arm and 7.3 months for Bevacizumab Plus mFOLFOX6 arm.

Outcome Measure Data

Analysis Population Description

Safety analysis set, which included all randomized participants who received at least 1 dose of protocol treatment (ie, panitumumab, bevacizumab, or any component of mFOLFOX6).

Arm/Group Title	Panitumumab Plus mFOLFOX6	Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.	Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
Measure Participants	139	139
Any adverse event (AE)	139 97.9%	139 97.2%
AE with worst grade of 3	88 62%	78 54.5%
AE with worst grade of 4	31 21.8%	28 19.6%
AE with worst grade of 5	7 4.9%	9 6.3%
Serious adverse event (SAE)	61 43%	53 37.1%
AE leading to discontinuation of study drug	34 23.9%	37 25.9%
Any treatment-related adverse event (TRAE)	138 97.2%	136 95.1%
Treatment-related AE with worst grade of 3	92 64.8%	77 53.8%
Treatment-related AE with worst grade of 4	24 16.9%	25 17.5%
Treatment-related AE with worst grade of 5	3 2.1%	2 1.4%
Serious treatment-related adverse event	37 26.1%	28 19.6%
TRAE leading to discontinuation of study drug	28 19.7%	29 20.3%

Adverse Events

Time Frame	The time frame for adverse event reporting is from the first dose date to 30 days since the last dose date. The median time frame is 8.0 months for Panitumumab Plus Chemotherapy arm and 7.3 months for Bevacizumab Plus Chemotherapy arm.
Adverse Event Reporting Description	The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Arm/Group Title	Panitumumab Plus mFOLFOX6		Bevacizumab Plus mFOLFOX6
Arm/Group Description	Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.		Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.
All Cause Mortality
	Panitumumab Plus mFOLFOX6		Bevacizumab Plus mFOLFOX6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Panitumumab Plus mFOLFOX6		Bevacizumab Plus mFOLFOX6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/139 (43.9%)		53/139 (38.1%)
Blood and lymphatic system disorders
Febrile neutropenia	3/139 (2.2%)		3/139 (2.2%)
Leukopenia	1/139 (0.7%)		1/139 (0.7%)
Neutropenia	2/139 (1.4%)		2/139 (1.4%)
Cardiac disorders
Acute coronary syndrome	1/139 (0.7%)		0/139 (0%)
Cardiac arrest	1/139 (0.7%)		1/139 (0.7%)
Cardio-respiratory arrest	0/139 (0%)		1/139 (0.7%)
Myocardial infarction	0/139 (0%)		2/139 (1.4%)
Gastrointestinal disorders
Abdominal pain	0/139 (0%)		2/139 (1.4%)
Anal fistula	0/139 (0%)		2/139 (1.4%)
Colitis	1/139 (0.7%)		0/139 (0%)
Constipation	2/139 (1.4%)		0/139 (0%)
Diarrhoea	9/139 (6.5%)		1/139 (0.7%)
Gastritis	0/139 (0%)		1/139 (0.7%)
Gastrointestinal disorder	1/139 (0.7%)		0/139 (0%)
Gastrointestinal perforation	0/139 (0%)		2/139 (1.4%)
Gastrooesophageal reflux disease	2/139 (1.4%)		0/139 (0%)
Ileus	1/139 (0.7%)		3/139 (2.2%)
Inguinal hernia	0/139 (0%)		1/139 (0.7%)
Intestinal obstruction	2/139 (1.4%)		2/139 (1.4%)
Intestinal perforation	0/139 (0%)		2/139 (1.4%)
Large intestinal obstruction	0/139 (0%)		1/139 (0.7%)
Melaena	1/139 (0.7%)		0/139 (0%)
Nausea	1/139 (0.7%)		0/139 (0%)
Oesophagitis	1/139 (0.7%)		0/139 (0%)
Rectal perforation	1/139 (0.7%)		0/139 (0%)
Small intestinal perforation	0/139 (0%)		1/139 (0.7%)
Stomatitis	2/139 (1.4%)		0/139 (0%)
Upper gastrointestinal haemorrhage	0/139 (0%)		1/139 (0.7%)
Vomiting	1/139 (0.7%)		2/139 (1.4%)
General disorders
Adverse drug reaction	1/139 (0.7%)		0/139 (0%)
Chills	0/139 (0%)		1/139 (0.7%)
Fatigue	1/139 (0.7%)		0/139 (0%)
General physical health deterioration	1/139 (0.7%)		0/139 (0%)
Mucosal inflammation	1/139 (0.7%)		0/139 (0%)
Non-cardiac chest pain	0/139 (0%)		2/139 (1.4%)
Pyrexia	2/139 (1.4%)		4/139 (2.9%)
Thrombosis in device	1/139 (0.7%)		0/139 (0%)
Immune system disorders
Anaphylactic reaction	0/139 (0%)		1/139 (0.7%)
Hypersensitivity	1/139 (0.7%)		0/139 (0%)
Infections and infestations
Anal abscess	0/139 (0%)		1/139 (0.7%)
Device related sepsis	1/139 (0.7%)		0/139 (0%)
Endocarditis	0/139 (0%)		1/139 (0.7%)
Escherichia bacteraemia	1/139 (0.7%)		0/139 (0%)
Herpes zoster oticus	0/139 (0%)		1/139 (0.7%)
Infection	0/139 (0%)		2/139 (1.4%)
Infusion site infection	1/139 (0.7%)		0/139 (0%)
Meningoencephalitis herpetic	0/139 (0%)		1/139 (0.7%)
Orchitis	1/139 (0.7%)		0/139 (0%)
Perirectal abscess	1/139 (0.7%)		0/139 (0%)
Peritonitis	0/139 (0%)		1/139 (0.7%)
Pneumonia	2/139 (1.4%)		3/139 (2.2%)
Postoperative wound infection	1/139 (0.7%)		0/139 (0%)
Sepsis	3/139 (2.2%)		2/139 (1.4%)
Septic shock	0/139 (0%)		1/139 (0.7%)
Subcutaneous abscess	0/139 (0%)		1/139 (0.7%)
Urinary tract infection	1/139 (0.7%)		2/139 (1.4%)
Injury, poisoning and procedural complications
Ankle fracture	0/139 (0%)		1/139 (0.7%)
Face injury	0/139 (0%)		1/139 (0.7%)
Subdural haematoma	0/139 (0%)		1/139 (0.7%)
Toxicity to various agents	1/139 (0.7%)		0/139 (0%)
Wound haemorrhage	0/139 (0%)		1/139 (0.7%)
Investigations
Eastern Cooperative Oncology Group performance status worsened	0/139 (0%)		1/139 (0.7%)
Metabolism and nutrition disorders
Decreased appetite	1/139 (0.7%)		0/139 (0%)
Dehydration	3/139 (2.2%)		0/139 (0%)
Hypercalcaemia	0/139 (0%)		1/139 (0.7%)
Hyperglycaemia	0/139 (0%)		2/139 (1.4%)
Hyperkalaemia	1/139 (0.7%)		0/139 (0%)
Hypokalaemia	1/139 (0.7%)		0/139 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	1/139 (0.7%)		0/139 (0%)
Groin pain	0/139 (0%)		1/139 (0.7%)
Musculoskeletal pain	0/139 (0%)		1/139 (0.7%)
Trismus	1/139 (0.7%)		0/139 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer	1/139 (0.7%)		0/139 (0%)
Nervous system disorders
Convulsion	1/139 (0.7%)		0/139 (0%)
Syncope	0/139 (0%)		4/139 (2.9%)
Transient ischaemic attack	0/139 (0%)		1/139 (0.7%)
Vertebrobasilar insufficiency	0/139 (0%)		1/139 (0.7%)
Psychiatric disorders
Mood altered	0/139 (0%)		1/139 (0.7%)
Panic attack	0/139 (0%)		1/139 (0.7%)
Substance abuse	1/139 (0.7%)		0/139 (0%)
Renal and urinary disorders
Renal failure	1/139 (0.7%)		1/139 (0.7%)
Renal failure acute	1/139 (0.7%)		1/139 (0.7%)
Ureteric obstruction	1/139 (0.7%)		1/139 (0.7%)
Reproductive system and breast disorders
Epididymitis	1/139 (0.7%)		0/139 (0%)
Pelvic pain	0/139 (0%)		1/139 (0.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/139 (0.7%)		0/139 (0%)
Pneumonia aspiration	1/139 (0.7%)		0/139 (0%)
Pulmonary embolism	7/139 (5%)		6/139 (4.3%)
Pulmonary venous thrombosis	0/139 (0%)		1/139 (0.7%)
Respiratory failure	1/139 (0.7%)		0/139 (0%)
Skin and subcutaneous tissue disorders
Nail bed inflammation	1/139 (0.7%)		0/139 (0%)
Rash	1/139 (0.7%)		0/139 (0%)
Vascular disorders
Deep vein thrombosis	4/139 (2.9%)		4/139 (2.9%)
Intra-abdominal haematoma	0/139 (0%)		1/139 (0.7%)
Jugular vein thrombosis	0/139 (0%)		1/139 (0.7%)
Superior vena cava syndrome	1/139 (0.7%)		0/139 (0%)
Thrombophlebitis superficial	1/139 (0.7%)		0/139 (0%)
Thrombosis	0/139 (0%)		1/139 (0.7%)
Other (Not Including Serious) Adverse Events
	Panitumumab Plus mFOLFOX6		Bevacizumab Plus mFOLFOX6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	139/139 (100%)		139/139 (100%)
Blood and lymphatic system disorders
Anaemia	24/139 (17.3%)		20/139 (14.4%)
Leukopenia	10/139 (7.2%)		9/139 (6.5%)
Neutropenia	63/139 (45.3%)		66/139 (47.5%)
Thrombocytopenia	34/139 (24.5%)		17/139 (12.2%)
Eye disorders
Conjunctivitis	16/139 (11.5%)		4/139 (2.9%)
Lacrimation increased	7/139 (5%)		6/139 (4.3%)
Vision blurred	8/139 (5.8%)		3/139 (2.2%)
Gastrointestinal disorders
Abdominal pain	25/139 (18%)		25/139 (18%)
Abdominal pain upper	11/139 (7.9%)		12/139 (8.6%)
Cheilitis	8/139 (5.8%)		0/139 (0%)
Constipation	44/139 (31.7%)		44/139 (31.7%)
Diarrhoea	84/139 (60.4%)		84/139 (60.4%)
Dyspepsia	14/139 (10.1%)		15/139 (10.8%)
Flatulence	10/139 (7.2%)		6/139 (4.3%)
Haemorrhoids	4/139 (2.9%)		7/139 (5%)
Nausea	75/139 (54%)		83/139 (59.7%)
Rectal haemorrhage	7/139 (5%)		6/139 (4.3%)
Stomatitis	46/139 (33.1%)		31/139 (22.3%)
Vomiting	43/139 (30.9%)		38/139 (27.3%)
General disorders
Asthenia	50/139 (36%)		44/139 (31.7%)
Chills	11/139 (7.9%)		12/139 (8.6%)
Fatigue	50/139 (36%)		65/139 (46.8%)
Mucosal inflammation	49/139 (35.3%)		21/139 (15.1%)
Oedema peripheral	18/139 (12.9%)		13/139 (9.4%)
Pyrexia	21/139 (15.1%)		30/139 (21.6%)
Temperature intolerance	7/139 (5%)		11/139 (7.9%)
Infections and infestations
Bronchitis	4/139 (2.9%)		8/139 (5.8%)
Nasopharyngitis	7/139 (5%)		8/139 (5.8%)
Paronychia	25/139 (18%)		2/139 (1.4%)
Respiratory tract infection	7/139 (5%)		5/139 (3.6%)
Rhinitis	9/139 (6.5%)		5/139 (3.6%)
Upper respiratory tract infection	4/139 (2.9%)		9/139 (6.5%)
Urinary tract infection	9/139 (6.5%)		10/139 (7.2%)
Injury, poisoning and procedural complications
Infusion related reaction	9/139 (6.5%)		6/139 (4.3%)
Investigations
Platelet count decreased	10/139 (7.2%)		5/139 (3.6%)
Weight decreased	31/139 (22.3%)		16/139 (11.5%)
Weight increased	8/139 (5.8%)		2/139 (1.4%)
Metabolism and nutrition disorders
Decreased appetite	56/139 (40.3%)		44/139 (31.7%)
Dehydration	18/139 (12.9%)		10/139 (7.2%)
Hypoalbuminaemia	3/139 (2.2%)		7/139 (5%)
Hypocalcaemia	12/139 (8.6%)		5/139 (3.6%)
Hypokalaemia	38/139 (27.3%)		18/139 (12.9%)
Hypomagnesaemia	57/139 (41%)		9/139 (6.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/139 (5.8%)		14/139 (10.1%)
Back pain	12/139 (8.6%)		14/139 (10.1%)
Muscular weakness	3/139 (2.2%)		7/139 (5%)
Musculoskeletal chest pain	3/139 (2.2%)		7/139 (5%)
Musculoskeletal pain	7/139 (5%)		9/139 (6.5%)
Neck pain	2/139 (1.4%)		7/139 (5%)
Pain in extremity	12/139 (8.6%)		18/139 (12.9%)
Nervous system disorders
Dizziness	16/139 (11.5%)		15/139 (10.8%)
Dysaesthesia	13/139 (9.4%)		23/139 (16.5%)
Dysgeusia	31/139 (22.3%)		27/139 (19.4%)
Headache	12/139 (8.6%)		15/139 (10.8%)
Neuropathy peripheral	44/139 (31.7%)		45/139 (32.4%)
Neurotoxicity	15/139 (10.8%)		13/139 (9.4%)
Paraesthesia	25/139 (18%)		31/139 (22.3%)
Peripheral sensory neuropathy	24/139 (17.3%)		24/139 (17.3%)
Polyneuropathy	18/139 (12.9%)		16/139 (11.5%)
Psychiatric disorders
Anxiety	10/139 (7.2%)		8/139 (5.8%)
Insomnia	14/139 (10.1%)		19/139 (13.7%)
Renal and urinary disorders
Proteinuria	15/139 (10.8%)		11/139 (7.9%)
Respiratory, thoracic and mediastinal disorders
Cough	17/139 (12.2%)		13/139 (9.4%)
Dysphonia	4/139 (2.9%)		8/139 (5.8%)
Dyspnoea	15/139 (10.8%)		18/139 (12.9%)
Epistaxis	29/139 (20.9%)		32/139 (23%)
Oropharyngeal pain	4/139 (2.9%)		12/139 (8.6%)
Pulmonary embolism	7/139 (5%)		8/139 (5.8%)
Rhinorrhoea	3/139 (2.2%)		13/139 (9.4%)
Skin and subcutaneous tissue disorders
Acne	35/139 (25.2%)		1/139 (0.7%)
Alopecia	25/139 (18%)		21/139 (15.1%)
Dermatitis acneiform	27/139 (19.4%)		1/139 (0.7%)
Dry skin	53/139 (38.1%)		12/139 (8.6%)
Erythema	11/139 (7.9%)		2/139 (1.4%)
Exfoliative rash	11/139 (7.9%)		2/139 (1.4%)
Hypertrichosis	9/139 (6.5%)		0/139 (0%)
Nail disorder	12/139 (8.6%)		6/139 (4.3%)
Palmar-plantar erythrodysaesthesia syndrome	22/139 (15.8%)		14/139 (10.1%)
Pruritus	16/139 (11.5%)		4/139 (2.9%)
Rash	86/139 (61.9%)		9/139 (6.5%)
Skin fissures	29/139 (20.9%)		1/139 (0.7%)
Skin toxicity	8/139 (5.8%)		0/139 (0%)
Vascular disorders
Deep vein thrombosis	5/139 (3.6%)		10/139 (7.2%)
Haematoma	1/139 (0.7%)		7/139 (5%)
Hypertension	6/139 (4.3%)		35/139 (25.2%)
Hypotension	7/139 (5%)		6/139 (4.3%)

Limitations/Caveats

[Not Specified]

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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.