Colorectal Cancer
Conditions
Brief summary
This observational study will evaluate the safety and efficacy of Bevacizumab in combination with 5-Fluorouracil based chemotherapy as first-line and second-line therapy in Chinese participants with metastatic colorectal cancer. Data will be collected from each participant for up to 3 years.
Interventions
None listed
Sponsors
Hoffmann-La Roche
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult Chinese participants, \>/= 18 years of age * Histologically confirmed and previously untreated metastatic colorectal cancer * Initiated on treatment with Bevacizumab (in combination with 5-FU based chemotherapy) according to locally approved Bevacizumab China package insert * Documented participant with medical records
Exclusion criteria
* Recent history of serious hemorrhage or hemoptysis of \>/= 1/2 teaspoon of red blood * Proteinuria at baseline (\>/=2 grams / 24 hours) * Major surgical procedure within 28 days prior to study treatment start, not fully healed wounds * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events | 36 months | An adverse event (AE) is defined as any untoward medical occurrence in a participant after administration of a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. |
| Percentage of Participants With Serious Adverse Events | 36 months | A Serious Adverse Event (SAE) was any untoward medical occurrence that at any dose was fatal, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant, or required intervention to prevent one or other of the outcomes listed above. |
| Percentage of Participants With Adverse Events of Special Interest | 36 months | — |
| Percentage of Participants With Bevacizumab-Related Adverse Events | 36 months | — |
| Percentage of Participants With Bevacizumab-related Serious Adverse Events | 36 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| One-year Progression-free Survival Rate Per KRAS Subgroup | 1 year | One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year. Results are reported per participants' Kirsten Rat Sarcoma Viral (KRAS) oncogene subgroup. |
| One-year Survival Rate by the KRAS Subgroup | 1 year | — |
| Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | Up to 36 Months | Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions. Results are reported per participants' chemotherapy regimen subgroup. |
| Percentage of Participants Achieving an Overall Response | 36 months | Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions. |
| One-year Survival Rate by the Chemotherapy Regimen Subgroup | 1 year | — |
| Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Up to 36 Months | Quality of life was assessed at baseline and every three months after treatment by the EORTC QLQ-C30 questionnaire. The possible score range was 0 to 100, with a higher score indicating better functioning. |
| One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | 1 year | One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year. Results are reported per participants' chemotherapy regimen subgroup. |
| Progression-free Survival | 36 months | Progression-free-survival (PFS) was defined as the time from the date when the participant signed the informed consent form to the time of first documented disease progression or death, whichever occurred first. |
| One-year Progression-free Survival Rate | 1 year | One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year. |
| One-year Survival Rate | 1 year | — |
| Percentage of Participants Achieving an Overall Response Per Kirsten Rat Sarcoma Viral (KRAS) Oncogene Subgroup | 36 months | Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions. Results are reported per participants' Kirsten Rat Sarcoma Viral (KRAS) oncogene subgroup. |
Countries
China
Participant flow
Pre-assignment details
Three enrolled participants received third-line therapy and were not included in the evaluable population.
Participants by arm
| Arm | Count |
|---|---|
| First Line Treatment Participants received bevacizumab in combination with 5-FU based chemotherapy as a first line therapy. | 453 |
| Second Line Treatment Participants received bevacizumab in combination with 5-FU based chemotherapy as a second line therapy. | 153 |
| Total | 606 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease Progression | 2 | 2 |
| Overall Study | Lost to Follow-up | 100 | 37 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Reason Not Specified | 4 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | First Line Treatment | Second Line Treatment | Total |
|---|---|---|---|
| Age, Continuous | 55.7 years STANDARD_DEVIATION 11.9 | 54.5 years STANDARD_DEVIATION 11.9 | 55.4 years STANDARD_DEVIATION 11.9 |
| Region of Enrollment China | 453 participants | 153 participants | 606 participants |
| Sex: Female, Male Female | 183 Participants | 53 Participants | 236 Participants |
| Sex: Female, Male Male | 270 Participants | 100 Participants | 370 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 450 / 606 |
| serious Total, serious adverse events | 29 / 606 |
Outcome results
Primary
Percentage of Participants With Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a participant after administration of a pharmaceutical product and which did not necessarily have a causal relationship with this treatment.
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| First Line Treatment | Percentage of Participants With Adverse Events | 76.4 percentage of participants |
| Second Line Treatment | Percentage of Participants With Adverse Events | 68.0 percentage of participants |
Primary
Percentage of Participants With Adverse Events of Special Interest
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| First Line Treatment | Percentage of Participants With Adverse Events of Special Interest | 9.1 percentage of participants |
| Second Line Treatment | Percentage of Participants With Adverse Events of Special Interest | 5.9 percentage of participants |
Primary
Percentage of Participants With Bevacizumab-Related Adverse Events
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| First Line Treatment | Percentage of Participants With Bevacizumab-Related Adverse Events | 54.5 percentage of participants |
| Second Line Treatment | Percentage of Participants With Bevacizumab-Related Adverse Events | 45.8 percentage of participants |
Primary
Percentage of Participants With Bevacizumab-related Serious Adverse Events
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| First Line Treatment | Percentage of Participants With Bevacizumab-related Serious Adverse Events | 3.1 percentage of participants |
| Second Line Treatment | Percentage of Participants With Bevacizumab-related Serious Adverse Events | 2.0 percentage of participants |
Primary
Percentage of Participants With Serious Adverse Events
A Serious Adverse Event (SAE) was any untoward medical occurrence that at any dose was fatal, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant, or required intervention to prevent one or other of the outcomes listed above.
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| First Line Treatment | Percentage of Participants With Serious Adverse Events | 4.9 percentage of participants |
| Second Line Treatment | Percentage of Participants With Serious Adverse Events | 4.6 percentage of participants |
Secondary
One-year Progression-free Survival Rate
One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| First Line Treatment | One-year Progression-free Survival Rate | 34.2 percentage of participants |
| Second Line Treatment | One-year Progression-free Survival Rate | 29.9 percentage of participants |
Secondary
One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup
One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year. Results are reported per participants' chemotherapy regimen subgroup.
Time frame: 1 year
Population: Participants with known prior chemotherapy regimens were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Line Treatment | One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | FOLFOX | 38.9 percentage of participants |
| First Line Treatment | One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | XELOX | 44.9 percentage of participants |
| First Line Treatment | One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | XELIRI | 13.3 percentage of participants |
| First Line Treatment | One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | Others | 19.5 percentage of participants |
| First Line Treatment | One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | IFL | 29.1 percentage of participants |
| Second Line Treatment | One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | Others | 16.7 percentage of participants |
| Second Line Treatment | One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | IFL | 32.2 percentage of participants |
| Second Line Treatment | One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | FOLFOX | 38.1 percentage of participants |
| Second Line Treatment | One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | XELIRI | 20.0 percentage of participants |
| Second Line Treatment | One-year Progression-free Survival Rate Per Chemotherapy Regimen Subgroup | XELOX | 20.8 percentage of participants |
Secondary
One-year Progression-free Survival Rate Per KRAS Subgroup
One year progression-free survival rate was defined as the percentage of participants who were free of progression or death from the date when the participant signed the informed consent form to one year. Results are reported per participants' Kirsten Rat Sarcoma Viral (KRAS) oncogene subgroup.
Time frame: 1 year
Population: Participants with known KRAS status were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Line Treatment | One-year Progression-free Survival Rate Per KRAS Subgroup | Wild-type | 45.2 percentage of participants |
| First Line Treatment | One-year Progression-free Survival Rate Per KRAS Subgroup | Mutant-type | 19.5 percentage of participants |
| Second Line Treatment | One-year Progression-free Survival Rate Per KRAS Subgroup | Wild-type | 31.3 percentage of participants |
| Second Line Treatment | One-year Progression-free Survival Rate Per KRAS Subgroup | Mutant-type | 0 percentage of participants |
Secondary
One-year Survival Rate
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| First Line Treatment | One-year Survival Rate | 68.7 percentage of participants |
| Second Line Treatment | One-year Survival Rate | 69.1 percentage of participants |
Secondary
One-year Survival Rate by the Chemotherapy Regimen Subgroup
Time frame: 1 year
Population: Participants with known prior chemotherapy regimens were evaluated
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Line Treatment | One-year Survival Rate by the Chemotherapy Regimen Subgroup | IFL | 70.8 percentage of participants |
| First Line Treatment | One-year Survival Rate by the Chemotherapy Regimen Subgroup | XELOX | 75.2 percentage of participants |
| First Line Treatment | One-year Survival Rate by the Chemotherapy Regimen Subgroup | XELIRI | 66.7 percentage of participants |
| First Line Treatment | One-year Survival Rate by the Chemotherapy Regimen Subgroup | Others | 64.7 percentage of participants |
| First Line Treatment | One-year Survival Rate by the Chemotherapy Regimen Subgroup | FOLFOX | 66.6 percentage of participants |
| Second Line Treatment | One-year Survival Rate by the Chemotherapy Regimen Subgroup | Others | 60.0 percentage of participants |
| Second Line Treatment | One-year Survival Rate by the Chemotherapy Regimen Subgroup | FOLFOX | 71.6 percentage of participants |
| Second Line Treatment | One-year Survival Rate by the Chemotherapy Regimen Subgroup | IFL | 71.4 percentage of participants |
| Second Line Treatment | One-year Survival Rate by the Chemotherapy Regimen Subgroup | XELIRI | 20.8 percentage of participants |
| Second Line Treatment | One-year Survival Rate by the Chemotherapy Regimen Subgroup | XELOX | 0 percentage of participants |
Secondary
One-year Survival Rate by the KRAS Subgroup
Time frame: 1 year
Population: Participants with known KRAS status were evaluated
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Line Treatment | One-year Survival Rate by the KRAS Subgroup | Mutant-type | 57.9 percentage of participants |
| First Line Treatment | One-year Survival Rate by the KRAS Subgroup | Wild-type | 81.0 percentage of participants |
| Second Line Treatment | One-year Survival Rate by the KRAS Subgroup | Mutant-type | 33.9 percentage of participants |
| Second Line Treatment | One-year Survival Rate by the KRAS Subgroup | Wild-type | 69.1 percentage of participants |
Secondary
Percentage of Participants Achieving an Overall Response
Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions.
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| First Line Treatment | Percentage of Participants Achieving an Overall Response | 21.0 percentage of participants |
| Second Line Treatment | Percentage of Participants Achieving an Overall Response | 10.5 percentage of participants |
Secondary
Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup
Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions. Results are reported per participants' chemotherapy regimen subgroup.
Time frame: Up to 36 Months
Population: Participants with known prior chemotherapy regimens were evaluated
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Line Treatment | Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | IFL | 18.5 percentage of participants |
| First Line Treatment | Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | XELOX | 32.1 percentage of participants |
| First Line Treatment | Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | XELIRI | 45.5 percentage of participants |
| First Line Treatment | Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | Others | 5.8 percentage of participants |
| First Line Treatment | Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | FOLFOX | 25.7 percentage of participants |
| Second Line Treatment | Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | Others | 7.1 percentage of participants |
| Second Line Treatment | Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | FOLFOX | 15.2 percentage of participants |
| Second Line Treatment | Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | IFL | 10.9 percentage of participants |
| Second Line Treatment | Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | XELIRI | 14.3 percentage of participants |
| Second Line Treatment | Percentage of Participants Achieving an Overall Response by the Chemotherapy Regimen Subgroup | XELOX | 0 percentage of participants |
Secondary
Percentage of Participants Achieving an Overall Response Per Kirsten Rat Sarcoma Viral (KRAS) Oncogene Subgroup
Overall response was defined as complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, all non-target lesions, and no new lesions. PR: At least a 30% decrease in the sum of the diameters of target lesions, no progression in non-target lesions, and no new lesions. Results are reported per participants' Kirsten Rat Sarcoma Viral (KRAS) oncogene subgroup.
Time frame: 36 months
Population: Participants with known KRAS status were evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Line Treatment | Percentage of Participants Achieving an Overall Response Per Kirsten Rat Sarcoma Viral (KRAS) Oncogene Subgroup | Wild-type | 18.6 percentage of participants |
| First Line Treatment | Percentage of Participants Achieving an Overall Response Per Kirsten Rat Sarcoma Viral (KRAS) Oncogene Subgroup | Mutant-type | 10.7 percentage of participants |
| Second Line Treatment | Percentage of Participants Achieving an Overall Response Per Kirsten Rat Sarcoma Viral (KRAS) Oncogene Subgroup | Wild-type | 10.3 percentage of participants |
| Second Line Treatment | Percentage of Participants Achieving an Overall Response Per Kirsten Rat Sarcoma Viral (KRAS) Oncogene Subgroup | Mutant-type | 4.8 percentage of participants |
Secondary
Progression-free Survival
Progression-free-survival (PFS) was defined as the time from the date when the participant signed the informed consent form to the time of first documented disease progression or death, whichever occurred first.
Time frame: 36 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Line Treatment | Progression-free Survival | 9.1 months |
| Second Line Treatment | Progression-free Survival | 8.1 months |
Secondary
Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire
Quality of life was assessed at baseline and every three months after treatment by the EORTC QLQ-C30 questionnaire. The possible score range was 0 to 100, with a higher score indicating better functioning.
Time frame: Up to 36 Months
Population: Evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| First Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 3 (n=80,21) | 59.79 score on a scale | Standard Deviation 18.073 |
| First Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 6 (n=15,5) | 57.22 score on a scale | Standard Deviation 14.389 |
| First Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 2 (n=159,44) | 62.89 score on a scale | Standard Deviation 15.875 |
| First Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 7 (n=11,4) | 56.82 score on a scale | Standard Deviation 16.168 |
| First Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 4 (n=50,12) | 54.83 score on a scale | Standard Deviation 22.718 |
| First Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 8 (n=7,3) | 60.72 score on a scale | Standard Deviation 14.205 |
| First Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 9 (n=4,1) | 45.83 score on a scale | Standard Deviation 15.96 |
| First Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Baseline (n=248,67) | 63.68 score on a scale | Standard Deviation 18.02 |
| First Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 10 (n=1,0) | 50.00 score on a scale | — |
| First Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 5 (n=26,9) | 57.05 score on a scale | Standard Deviation 15.758 |
| Second Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 10 (n=1,0) | NA score on a scale | — |
| Second Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Baseline (n=248,67) | 65.67 score on a scale | Standard Deviation 14.103 |
| Second Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 2 (n=159,44) | 64.96 score on a scale | Standard Deviation 17.105 |
| Second Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 3 (n=80,21) | 56.35 score on a scale | Standard Deviation 19.168 |
| Second Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 4 (n=50,12) | 61.11 score on a scale | Standard Deviation 14.36 |
| Second Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 5 (n=26,9) | 62.96 score on a scale | Standard Deviation 16.724 |
| Second Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 6 (n=15,5) | 73.33 score on a scale | Standard Deviation 16.03 |
| Second Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 7 (n=11,4) | 72.92 score on a scale | Standard Deviation 15.773 |
| Second Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 9 (n=4,1) | 66.67 score on a scale | — |
| Second Line Treatment | Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire | Visit 8 (n=7,3) | 66.67 score on a scale | Standard Deviation 8.335 |