Colon Cancer, Colorectal Cancer, Metastatic Colorectal Cancer, Rectal Cancer
Conditions
Keywords
Colon Cancer, Colorectal Cancer, Rectal Cancer, Panitumumab, Vectibix, modified FOLFOX 6, mFOLFOX 6, FOLFOX, Bevacizumab, Avastin, First-Line, metastatic
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.
Interventions
DRUGPanitumumab
Panitumumab is a fully human immunoglobulin G (IgG)2 monoclonal antibody antagonist directed against human Epidermal Growth Factor receptor (EGFr).
DRUGBevacizumab
Bevacizumab is a humanized monoclonal IgG1 antibody that is directed against Vascular Endothelial Growth Factor (VEGF).
DRUGmFOLFOX6
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.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Belgium, Canada, Germany, Italy, Spain, United States
Participant flow
Recruitment details
First patient was enrolled on 24 April 2009; last patient was enrolled on 09 December 2011.
Participants by arm
| Arm | Count |
|---|---|
| Panitumumab Plus mFOLFOX6 Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle. | 142 |
| Bevacizumab Plus mFOLFOX6 Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle. | 143 |
| Total | 285 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive study drug | 3 | 4 |
| Overall Study | Still in treatment | 25 | 17 |
Baseline characteristics
| Characteristic | Bevacizumab Plus mFOLFOX6 | Total | Panitumumab Plus mFOLFOX6 |
|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 9.8 | 61.0 years STANDARD_DEVIATION 10.1 | 61.6 years STANDARD_DEVIATION 10.4 |
| Prior Adjuvant Oxaliplatin Therapy No | 129 participants | 257 participants | 128 participants |
| Prior Adjuvant Oxaliplatin Therapy Yes | 14 participants | 28 participants | 14 participants |
| Race/Ethnicity, Customized Asian | 4 participants | 4 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 6 participants | 15 participants | 9 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 participants | 7 participants | 2 participants |
| Race/Ethnicity, Customized Japanese | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White or Caucasian | 127 participants | 258 participants | 131 participants |
| RAS and BRAF Mutation Status BRAF wild-type | 108 participants | 211 participants | 103 participants |
| RAS and BRAF Mutation Status RAS/BRAF wild-type | 79 participants | 156 participants | 77 participants |
| RAS and BRAF Mutation Status RAS Wild-type | 82 participants | 170 participants | 88 participants |
| RAS and BRAF Mutation Status Sample acceptance failure | 7 participants | 15 participants | 8 participants |
| RAS and BRAF Mutation Status Testing not performed | 18 participants | 31 participants | 13 participants |
| Sex: Female, Male Female | 47 Participants | 103 Participants | 56 Participants |
| Sex: Female, Male Male | 96 Participants | 182 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 139 / 139 | 139 / 139 |
| serious Total, serious adverse events | 61 / 139 | 53 / 139 |
Outcome results
Primary
Progression-free Survival (PFS)
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.
Population: Intent-to-treat (ITT) analysis set (all randomized participants)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Progression-free Survival (PFS) | 10.9 months |
| Bevacizumab Plus mFOLFOX6 | Progression-free Survival (PFS) | 10.1 months |
p-value: 0.353195% CI: [0.651, 1.166]Stratified Cox proportional hazards
Secondary
Duration of Response
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.
Population: Evaluable for Local Tumor Response Analysis Set: Responders
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Duration of Response | 10.0 months |
| Bevacizumab Plus mFOLFOX6 | Duration of Response | 9.0 months |
Secondary
Number of Participants With Adverse Events (AEs)
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.
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Any adverse event (AE) | 139 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | AE with worst grade of 3 | 88 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | AE with worst grade of 4 | 31 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | AE with worst grade of 5 | 7 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Serious adverse event (SAE) | 61 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of study drug | 34 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Any treatment-related adverse event (TRAE) | 138 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Treatment-related AE with worst grade of 3 | 92 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Treatment-related AE with worst grade of 4 | 24 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Treatment-related AE with worst grade of 5 | 3 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Serious treatment-related adverse event | 37 participants |
| Panitumumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | TRAE leading to discontinuation of study drug | 28 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Serious treatment-related adverse event | 28 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Any adverse event (AE) | 139 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Any treatment-related adverse event (TRAE) | 136 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | AE with worst grade of 3 | 78 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Treatment-related AE with worst grade of 5 | 2 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | AE with worst grade of 4 | 28 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Treatment-related AE with worst grade of 3 | 77 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | AE with worst grade of 5 | 9 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | TRAE leading to discontinuation of study drug | 29 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Serious adverse event (SAE) | 53 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | Treatment-related AE with worst grade of 4 | 25 participants |
| Bevacizumab Plus mFOLFOX6 | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of study drug | 37 participants |
Secondary
Overall Survival
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.
Population: Intent-to-treat analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Overall Survival | NA months |
| Bevacizumab Plus mFOLFOX6 | Overall Survival | 25.4 months |
p-value: 0.138695% CI: [0.47, 1.111]Stratified Cox proportional hazards
Secondary
Overall Survival in Participants With Wild-type RAS
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.
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Overall Survival in Participants With Wild-type RAS | NA months |
| Bevacizumab Plus mFOLFOX6 | Overall Survival in Participants With Wild-type RAS | 29.0 months |
p-value: 0.093495% CI: [0.337, 1.088]Stratified Cox proportional hazards
Secondary
Overall Survival in Participants With Wild-type RAS / BRAF
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.
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Overall Survival in Participants With Wild-type RAS / BRAF | NA months |
| Bevacizumab Plus mFOLFOX6 | Overall Survival in Participants With Wild-type RAS / BRAF | 29.0 months |
p-value: 0.023595% CI: [0.239, 0.902]Stratified Cox proportional hazards
Secondary
Percentage of Participants With an Objective Response
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.
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Percentage of Participants With an Objective Response | 57.75 percentage of participants |
| Bevacizumab Plus mFOLFOX6 | Percentage of Participants With an Objective Response | 53.52 percentage of participants |
p-value: 0.549795% CI: [0.72, 1.95]Stratified exact test
Secondary
Percentage of Participants With an Objective Response for Participants With Wild-type RAS
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.
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Percentage of Participants With an Objective Response for Participants With Wild-type RAS | 63.64 percentage of participants |
| Bevacizumab Plus mFOLFOX6 | Percentage of Participants With an Objective Response for Participants With Wild-type RAS | 60.49 percentage of participants |
p-value: 0.942695% CI: [0.55, 2.12]Stratified exact test
Secondary
Percentage of Participants With an Objective Response for Participants With Wild-type RAS / BRAF
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.
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Percentage of Participants With an Objective Response for Participants With Wild-type RAS / BRAF | 63.64 percentage of participants |
| Bevacizumab Plus mFOLFOX6 | Percentage of Participants With an Objective Response for Participants With Wild-type RAS / BRAF | 61.54 percentage of participants |
p-value: 195% CI: [0.52, 2.15]Stratified exact test
Secondary
Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)
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.
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) | 13.1 months |
| Bevacizumab Plus mFOLFOX6 | Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) | 9.7 months |
p-value: 0.008395% CI: [0.386, 0.869]Stratified Cox proportional hazards
Secondary
Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS)
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.
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS) | 13.0 months |
| Bevacizumab Plus mFOLFOX6 | Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS) | 9.5 months |
p-value: 0.028695% CI: [0.444, 0.956]Stratified Cox proportional hazards
Secondary
Resection Rate
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.
Population: Intent-to-treat analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Resection Rate | 12.68 percentage of participants |
| Bevacizumab Plus mFOLFOX6 | Resection Rate | 11.19 percentage of participants |
Secondary
Time to Disease Progression
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.
Population: Intent-to-treat analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Time to Disease Progression | 11.0 months |
| Bevacizumab Plus mFOLFOX6 | Time to Disease Progression | 11.1 months |
p-value: 0.386195% CI: [0.645, 1.185]Stratified Cox proportional hazards
Secondary
Time to Initial Objective Response
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.
Population: Evaluable for Local Tumor Response Analysis Set: Responders
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab Plus mFOLFOX6 | Time to Initial Objective Response | 1.8 months |
| Bevacizumab Plus mFOLFOX6 | Time to Initial Objective Response | 1.9 months |