Colorectal Cancer
Conditions
Brief summary
This observational study will evaluate the efficacy and safety of bevacizumab as first-line treatment in participants with colorectal cancer and potentially resectable liver metastases.
Interventions
DRUGBevacizumab
Participants with mCRC and having exclusively liver or liver and lung metastases who were receiving bevacizumab as part of first line treatment for potentially resectable liver metastases as per treating physician's discretion will be observed. All concomitant medications as used in routine clinical practice are allowed.
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
* Participants with colorectal cancer with exclusively hepatic or hepatic and pulmonary metastases * First-line treatment with bevacizumab for potentially resectable metastatic disease
Exclusion criteria
* Outright resectable disease * Clearly inoperable disease * Participation in a clinical trial evaluating a cytotoxic anticancer treatment and/or an innovative therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Without Detectable Metastatic Disease After Secondary Resection Post Surgery | Baseline up to 36 months | Secondary resection involves removal of all detectable metastases at surgery including participants with missing metastases left in place. Percentage of participants without detectable metastatic disease after secondary resection removing all detectable metastases at surgery (including participants with disappeared metastases left in place \[missing metastases\]) was reported. Metastases was detected using computed tomography (CT) scan or magnetic resonance imaging (MRI). |
| Percentage of Participants Without Detectable Metastatic Disease After a Complete Response Without Surgery | Baseline up to 36 months | The percentage of participants with no detectable metastatic disease after a complete response without surgery (missing metastasis) was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Duration of First Line Bevacizumab Treatment at Day 0 | Day 0 | — |
| Percentage of Participants With Different Previous Therapies at Day 0 | Day 0 | Previous therapies included neoadjuvant treatment (chemotherapy or chemotherapy + radiotherapy) and adjuvant treatment (FOLFOX \[folinic acid+5-fluorouracil+oxaliplatin\], LV5FU2 \[leucovorin+5-Fluorouracil\], capecitabine, or any other adjuvant treatment). Only participants who received neoadjuvant treatment and adjuvant treatment was reported. |
| Mean Number of Cumulated Cycles of Bevacizumab Over the Study Period | Baseline up to 36 months | — |
| Percentage of Participants Who Received at Least One Chemotherapy Over the Study Period | Baseline up to 36 months | — |
| Percentage of Participants With at Least One Comorbidity Post Bevacizumab Treatment | Baseline up to 36 months | Percentage of participants who had any concurrent disease (comorbidity) was reported. Comorbidities included gastrointestinal disease, other cardiovascular disease, and other medical history and comorbidities (other than those which are specified above). Same participant may be counted in more than one category. |
| Percentage of Participants With Disease Progression or Death | Baseline until disease progression or death, whichever occurred first, assessed up to 36 months | Disease progression is defined at least a 20 percent (%) increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 millimeter (mm) or persistence of non-target lesions, or appearance of one or more new lesions. |
| Progression-free Survival (PFS) | Baseline until disease progression or death, whichever occurred first, assessed up to 36 months | Progression-free survival defined as the time elapsed between the Avastin start date and the date of first progressive disease (PD) or death. Kaplan-Meier estimate was used for evaluation. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions or appearance of one or more new lesions. |
| Percentage of Participants With Unresectability Criteria | Day 0 | — |
| Relapse-free Survival (RFS) | Baseline until disease progression or death, whichever occurred first, assessed up to 36 months | RFS was defined as the time elapsed between the last surgery removing all detectable metastases (A1 criterion \[participants without DMD after secondary resection removing all detectable metastases at surgery {including participants with missing metastases}\]) and the date of first PD or death. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions, or appearance of one or more new lesions. |
| Percentage of Participants Who Died | Baseline until death; assessed up to 36 months | — |
| Overall Survival (OS) | Baseline until death, assessed up to 36 months | OS time is defined as time between start of therapy and date of death. Kaplan-Meier estimate was used for evaluation. |
| Percentage of Participants With Histologically Viable Tumor Cells With Resected Non Detectable Hepatic and Pulmonary Metastases Post Surgery | Baseline up to 36 months | For the non-detectable liver and lung metastases the categorization based on rate of viable cells were as follows (no viable cells =0%, minimum =1 to 49%, maximum =50 to 100%). |
| Number of Cumulated Cycles of First Line Bevacizumab at Day 0 | Day 0 | — |
| Percentage of Participants With Different Doses of First Line Bevacizumab at Day 0 | Day 0 | — |
| Percentage of Participants With Disease Relapse | Baseline until disease progression or death, whichever occurred first, assessed up to 36 months | Relapse was defined as the presence of metastases post last surgery removing all detectable metastases (A1 criterion \[participants without detectable metastatic disease {DMD} after secondary resection removing all detectable metastases at surgery {including participants with missing metastases}\]) and the date of first PD or death. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions, or appearance of one or more new lesions. |
| Percentage of Participants With at Least One Disease and Comorbidity at Day 0 | Day 0 | Percentage of participants who had any concurrent disease (comorbidity) at Day 0 was reported. Comorbidities included gastrointestinal disease, hypertension, other cardiovascular disease, and other medical history and comorbidities (other than those specified above). Same participant may be counted in more than one category. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab All participants with mCRC with exclusively liver or liver and lung metastases, who were receiving bevacizumab as part of first line treatment for potentially resectable liver metastases as per treating physician's discretion were observed. All concomitant medications as used in routine clinical practice were allowed. | 205 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 85 |
| Overall Study | Lost to Follow-up | 12 |
| Overall Study | Management by another medical team | 11 |
| Overall Study | Participant decision | 1 |
| Overall Study | Physician Decision | 4 |
Baseline characteristics
| Characteristic | Bevacizumab |
|---|---|
| Age, Continuous | 65.83 years STANDARD_DEVIATION 9.63 |
| Sex: Female, Male Female | 73 Participants |
| Sex: Female, Male Male | 132 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 75 / 210 |
| serious Total, serious adverse events | 71 / 210 |
Outcome results
Primary
Percentage of Participants Without Detectable Metastatic Disease After a Complete Response Without Surgery
The percentage of participants with no detectable metastatic disease after a complete response without surgery (missing metastasis) was reported.
Time frame: Baseline up to 36 months
Population: Efficacy population. Here number of participants analyzed represents the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Percentage of Participants Without Detectable Metastatic Disease After a Complete Response Without Surgery | 4.4 Percentage of participants |
Primary
Percentage of Participants Without Detectable Metastatic Disease After Secondary Resection Post Surgery
Secondary resection involves removal of all detectable metastases at surgery including participants with missing metastases left in place. Percentage of participants without detectable metastatic disease after secondary resection removing all detectable metastases at surgery (including participants with disappeared metastases left in place \[missing metastases\]) was reported. Metastases was detected using computed tomography (CT) scan or magnetic resonance imaging (MRI).
Time frame: Baseline up to 36 months
Population: Efficacy population. Here number of participants analyzed represents the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Percentage of Participants Without Detectable Metastatic Disease After Secondary Resection Post Surgery | 84.6 Percentage of participants |
Secondary
Mean Number of Cumulated Cycles of Bevacizumab Over the Study Period
Time frame: Baseline up to 36 months
Population: Efficacy population. Here number of participants analyzed represents the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bevacizumab | Mean Number of Cumulated Cycles of Bevacizumab Over the Study Period | 14.40 Cycles | Standard Deviation 10.8 |
Secondary
Number of Cumulated Cycles of First Line Bevacizumab at Day 0
Time frame: Day 0
Population: Efficacy population. Here number of participants analyzed represents the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bevacizumab | Number of Cumulated Cycles of First Line Bevacizumab at Day 0 | 10.20 cycles | Standard Deviation 7.79 |
Secondary
Overall Survival (OS)
OS time is defined as time between start of therapy and date of death. Kaplan-Meier estimate was used for evaluation.
Time frame: Baseline until death, assessed up to 36 months
Population: Efficacy population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Overall Survival (OS) | NA months |
Secondary
Percentage of Participants Who Died
Time frame: Baseline until death; assessed up to 36 months
Population: Efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Percentage of Participants Who Died | 41.0 Percentage of participants |
Secondary
Percentage of Participants Who Received at Least One Chemotherapy Over the Study Period
Time frame: Baseline up to 36 months
Population: Efficacy population. Here number of participants analyzed represents the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Percentage of Participants Who Received at Least One Chemotherapy Over the Study Period | 96.1 Percentage of participants |
Secondary
Percentage of Participants With at Least One Comorbidity Post Bevacizumab Treatment
Percentage of participants who had any concurrent disease (comorbidity) was reported. Comorbidities included gastrointestinal disease, other cardiovascular disease, and other medical history and comorbidities (other than those which are specified above). Same participant may be counted in more than one category.
Time frame: Baseline up to 36 months
Population: Analysis population consisted of participants with disappeared metastasis left in place with or without surgery. Here number of participants analyzed represents the number of participants evaluable for this outcome and 'n' represents the number of participants available for assessment at a given category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Percentage of Participants With at Least One Comorbidity Post Bevacizumab Treatment | Gastrointestinal disease | 8.0 Percentage of participants |
| Bevacizumab | Percentage of Participants With at Least One Comorbidity Post Bevacizumab Treatment | Other cardiovascular disease | 10.9 Percentage of participants |
| Bevacizumab | Percentage of Participants With at Least One Comorbidity Post Bevacizumab Treatment | Other medical history and comorbidities | 54.9 Percentage of participants |
| Bevacizumab | Percentage of Participants With at Least One Comorbidity Post Bevacizumab Treatment | Respiratory, thoracic and mediastinum disorders | 4.0 Percentage of participants |
Secondary
Percentage of Participants With at Least One Disease and Comorbidity at Day 0
Percentage of participants who had any concurrent disease (comorbidity) at Day 0 was reported. Comorbidities included gastrointestinal disease, hypertension, other cardiovascular disease, and other medical history and comorbidities (other than those specified above). Same participant may be counted in more than one category.
Time frame: Day 0
Population: Efficacy population. Here number of participants analyzed represents the number of participants evaluable for this outcome and 'n' represents the number of participants available for assessment at a given category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Percentage of Participants With at Least One Disease and Comorbidity at Day 0 | Gastrointestinal disease (n=201) | 7.5 Percentage of participants |
| Bevacizumab | Percentage of Participants With at Least One Disease and Comorbidity at Day 0 | Hypertension (n=202) | 41.6 Percentage of participants |
| Bevacizumab | Percentage of Participants With at Least One Disease and Comorbidity at Day 0 | Other cardiovascular disease (n=202) | 13.9 Percentage of participants |
| Bevacizumab | Percentage of Participants With at Least One Disease and Comorbidity at Day 0 | Other medical history and comorbidities (n=204) | 52.9 Percentage of participants |
Secondary
Percentage of Participants With Different Doses of First Line Bevacizumab at Day 0
Time frame: Day 0
Population: Efficacy population. Here, number of participants analyzed represents the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Percentage of Participants With Different Doses of First Line Bevacizumab at Day 0 | 5 milligrams per kilogram (mg/kg)/2 weeks | 94.9 Percentage of participants |
| Bevacizumab | Percentage of Participants With Different Doses of First Line Bevacizumab at Day 0 | 7.5 mg/kg/3 weeks | 3.1 Percentage of participants |
| Bevacizumab | Percentage of Participants With Different Doses of First Line Bevacizumab at Day 0 | 10 mg/kg/2 weeks | 2.0 Percentage of participants |
Secondary
Percentage of Participants With Different Previous Therapies at Day 0
Previous therapies included neoadjuvant treatment (chemotherapy or chemotherapy + radiotherapy) and adjuvant treatment (FOLFOX \[folinic acid+5-fluorouracil+oxaliplatin\], LV5FU2 \[leucovorin+5-Fluorouracil\], capecitabine, or any other adjuvant treatment). Only participants who received neoadjuvant treatment and adjuvant treatment was reported.
Time frame: Day 0
Population: Efficacy population. Here number of participants analysed represents the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Percentage of Participants With Different Previous Therapies at Day 0 | With Neoadjuvant Treatment | 29.1 Percentage of participants |
| Bevacizumab | Percentage of Participants With Different Previous Therapies at Day 0 | With Adjuvant Treatment | 52.7 Percentage of participants |
Secondary
Percentage of Participants With Disease Progression or Death
Disease progression is defined at least a 20 percent (%) increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 millimeter (mm) or persistence of non-target lesions, or appearance of one or more new lesions.
Time frame: Baseline until disease progression or death, whichever occurred first, assessed up to 36 months
Population: Efficacy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Percentage of Participants With Disease Progression or Death | 82.9 Percentage of participants |
Secondary
Percentage of Participants With Disease Relapse
Relapse was defined as the presence of metastases post last surgery removing all detectable metastases (A1 criterion \[participants without detectable metastatic disease {DMD} after secondary resection removing all detectable metastases at surgery {including participants with missing metastases}\]) and the date of first PD or death. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions, or appearance of one or more new lesions.
Time frame: Baseline until disease progression or death, whichever occurred first, assessed up to 36 months
Population: Efficacy population. Here number of participants analyzed signifies efficacy population with surgery removing all the detectable metastases.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Percentage of Participants With Disease Relapse | 76.1 Percentage of participants |
Secondary
Percentage of Participants With Histologically Viable Tumor Cells With Resected Non Detectable Hepatic and Pulmonary Metastases Post Surgery
For the non-detectable liver and lung metastases the categorization based on rate of viable cells were as follows (no viable cells =0%, minimum =1 to 49%, maximum =50 to 100%).
Time frame: Baseline up to 36 months
Population: Efficacy population. Here number of participants analyzed represents the overall number of participants evaluable for this outcome and 'n' represents the number of participants available for assessment at a given category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Percentage of Participants With Histologically Viable Tumor Cells With Resected Non Detectable Hepatic and Pulmonary Metastases Post Surgery | Hepatic metastases:No viable cell (0%)(n=70) | 4.3 Percentage of participants |
| Bevacizumab | Percentage of Participants With Histologically Viable Tumor Cells With Resected Non Detectable Hepatic and Pulmonary Metastases Post Surgery | Hepatic metastases:Minimum (1 - 49 %)(n=70) | 8.6 Percentage of participants |
| Bevacizumab | Percentage of Participants With Histologically Viable Tumor Cells With Resected Non Detectable Hepatic and Pulmonary Metastases Post Surgery | Hepatic metastases:Maximum (>=50%)(n=70) | 7.1 Percentage of participants |
| Bevacizumab | Percentage of Participants With Histologically Viable Tumor Cells With Resected Non Detectable Hepatic and Pulmonary Metastases Post Surgery | Hepatic metastases:Not Applicable(n=70) | 80.0 Percentage of participants |
| Bevacizumab | Percentage of Participants With Histologically Viable Tumor Cells With Resected Non Detectable Hepatic and Pulmonary Metastases Post Surgery | Pulmonary metastases:Maximum (>=50%)(n=80) | 1.3 Percentage of participants |
| Bevacizumab | Percentage of Participants With Histologically Viable Tumor Cells With Resected Non Detectable Hepatic and Pulmonary Metastases Post Surgery | Pulmonary metastases:Not Applicable(n=80) | 98.8 Percentage of participants |
Secondary
Percentage of Participants With Unresectability Criteria
Time frame: Day 0
Population: Efficacy population. Here number of participants analyzed represents the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Percentage of Participants With Unresectability Criteria | Oncological Reason (n=201) | 81.6 Percentage of participants |
| Bevacizumab | Percentage of Participants With Unresectability Criteria | Technical Reason (n=191) | 12.0 Percentage of participants |
| Bevacizumab | Percentage of Participants With Unresectability Criteria | Both Oncological and Technical Reason (n=191) | 10.5 Percentage of participants |
Secondary
Progression-free Survival (PFS)
Progression-free survival defined as the time elapsed between the Avastin start date and the date of first progressive disease (PD) or death. Kaplan-Meier estimate was used for evaluation. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions or appearance of one or more new lesions.
Time frame: Baseline until disease progression or death, whichever occurred first, assessed up to 36 months
Population: Efficacy population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Progression-free Survival (PFS) | 11.50 Months |
Secondary
Relapse-free Survival (RFS)
RFS was defined as the time elapsed between the last surgery removing all detectable metastases (A1 criterion \[participants without DMD after secondary resection removing all detectable metastases at surgery {including participants with missing metastases}\]) and the date of first PD or death. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions, or appearance of one or more new lesions.
Time frame: Baseline until disease progression or death, whichever occurred first, assessed up to 36 months
Population: Efficacy population. Here number of participants analyzed signifies efficacy population with surgery removing all the detectable metastases.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Relapse-free Survival (RFS) | 11.10 Months |
Secondary
Total Duration of First Line Bevacizumab Treatment at Day 0
Time frame: Day 0
Population: Efficacy population. Here number of participants analyzed represents the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Total Duration of First Line Bevacizumab Treatment at Day 0 | 4.67 months |