Colorectal Cancer
Conditions
Brief summary
This observational study will evaluate the efficacy and safety of different capecitabine based chemotherapies, alone or in combination with other therapies, as first line treatment of metastatic colorectal cancer in participants during everyday clinical practice.
Interventions
DRUGCapecitabine
First line capecitabine based oral tablet treatment in line with the effective Summary of Product Characteristics
DRUGChemotherapy
First line chemotherapy according to effective official Summary of Product Characteristics. The study protocol does not specify any particular therapy.
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 newly diagnosed mCRC who have started first-line capecitabine-based chemotherapy in accordance with the current Hungarian label
Exclusion criteria
* History of serious or unexpected reaction to fluoropyrimidine therapy * Hypersensitivity to the active ingredient of Xeloda or to any of the excipients of the product, or to fluorouracil * Known dihydropyrimidine dehydrogenase deficiency * Pregnancy or lactation * Inadequate bone marrow, hepatic or renal function * Treatment with sorivudine or its chemical analogues (for example, brivudine) * If any contraindication for any drug used in the combination treatment schedules is present, the drug in question cannot be used
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-free Survival (PFS) | Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254 | PFS was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and is defined as the time from the first dose of indicated treatment to disease progression (PD) or death, whichever occurred first. Participants who did not progress or died while being followed were censored on the date of the last visit. Participants without post-baseline tumor assessments were conservatively censored on the date of first study medication, which is PFS was assigned a value of 1 day. PD: at least 20 percent (%) increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 millimeter (mm); progression of existing non-target lesions; or presence of new lesions. Median PFS was estimated using Kaplan-Meier method. |
| PFS by Therapeutic Regimens | Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254 | PFS was assessed using RECIST v1.1 and is defined as the time from the first dose of indicated treatment to PD or death, whichever occurred first. Participants who did not progress or died while being followed were censored on the date of the last visit. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm; progression of existing non-target lesions; or presence of new lesions. Median PFS was estimated using Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Underwent Metastasectomy | Baseline up to 1254 days | Metastasectomy is the surgical removal of metastases, which are secondary cancerous growths that have spread from cancer originating in another organ in the body. |
| Percentage of Participants With Overall Response as Assessed by Investigator Using RECIST v1.1 | Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254 | Overall response is defined as a complete response (CR) or a partial response (PR) as determined by the Investigator using RECIST v1.1 on 2 consecutive occasions at least 6 weeks apart. Participants were evaluated for tumor response per RECIST v1.1 and assessed by computed tomography (CT) or magnetic resonance imaging (MRI):CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (\<) 10 mm). No new lesions.PR was defined as greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Percentage of Participants With Dose Modification of Capecitabine | Baseline up to 1254 days | — |
| Mean Duration of Capecitabine Therapy | Baseline up to 1254 days | — |
| Percentage of Participants With Clinical Benefit as Assessed Using RECIST v1.1 | Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254 | Clinical benefit was defined as having a confirmed CR, PR or stable disease (SD) for at least 24 weeks on study according to RECIST v1.1.CR: complete disappearance of all target lesions and non-target disease,with the exception of nodal disease.All nodes,both target and non-target, must decrease to normal (short axis \<10 mm).No new lesions.PR: \>=30% decrease under baseline of the sum of diameters of all target lesions.The short axis was used in the sum for target nodes,while the longest diameter was used in the sum for all other target lesions.No unequivocal progression of non-target disease.No new lesions.SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,taking as reference the smallest sum diameters while on study.PD:at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions,or presence of new lesions. |
Countries
Hungary
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| mCRC Participants Newly diagnosed mCRC participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen. | 690 |
| Total | 690 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 74 |
| Overall Study | Death | 29 |
| Overall Study | Disease progression | 373 |
| Overall Study | Lost to Follow-up | 48 |
| Overall Study | Major Protocol Violation | 192 |
| Overall Study | Other | 74 |
| Overall Study | Withdrawal by Subject | 92 |
Baseline characteristics
| Characteristic | mCRC Participants |
|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 10.51 |
| Sex: Female, Male Female | 289 Participants |
| Sex: Female, Male Male | 401 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 140 / 882 |
| serious Total, serious adverse events | 55 / 882 |
Outcome results
Primary
Median Progression-free Survival (PFS)
PFS was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and is defined as the time from the first dose of indicated treatment to disease progression (PD) or death, whichever occurred first. Participants who did not progress or died while being followed were censored on the date of the last visit. Participants without post-baseline tumor assessments were conservatively censored on the date of first study medication, which is PFS was assigned a value of 1 day. PD: at least 20 percent (%) increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 millimeter (mm); progression of existing non-target lesions; or presence of new lesions. Median PFS was estimated using Kaplan-Meier method.
Time frame: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| mCRC Participants | Median Progression-free Survival (PFS) | 254 Days |
Primary
PFS by Therapeutic Regimens
PFS was assessed using RECIST v1.1 and is defined as the time from the first dose of indicated treatment to PD or death, whichever occurred first. Participants who did not progress or died while being followed were censored on the date of the last visit. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm; progression of existing non-target lesions; or presence of new lesions. Median PFS was estimated using Kaplan-Meier method.
Time frame: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254
Population: ITT Population. Here, number (n)= number of participants evaluable for the specified therapeutic regimen.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| mCRC Participants | PFS by Therapeutic Regimens | Capecitabine monotherapy (n=246) | 194 Days |
| mCRC Participants | PFS by Therapeutic Regimens | Capecitabine + bevacizumab (n=25) | 391 Days |
| mCRC Participants | PFS by Therapeutic Regimens | Capecitabine + irinotecan (n=106) | 242 Days |
| mCRC Participants | PFS by Therapeutic Regimens | Capecitabine + irinotecan + bevacizumab (n= 91) | 392 Days |
| mCRC Participants | PFS by Therapeutic Regimens | Capecitabine + oxaliplatin (n=173) | 240 Days |
| mCRC Participants | PFS by Therapeutic Regimens | Capecitabine + oxaliplatin + bevacizumab (n= 49) | 392 Days |
Secondary
Mean Duration of Capecitabine Therapy
Time frame: Baseline up to 1254 days
Population: ITT Population. Here, N (number of participants analyzed) indicates the total number of participants who provided evaluable data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| mCRC Participants | Mean Duration of Capecitabine Therapy | 188.8 Days | Standard Deviation 171.71 |
Secondary
Percentage of Participants Who Underwent Metastasectomy
Metastasectomy is the surgical removal of metastases, which are secondary cancerous growths that have spread from cancer originating in another organ in the body.
Time frame: Baseline up to 1254 days
Population: ITT Population. Here, N (number of participants analyzed) indicates the total number of participants who provided evaluable data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| mCRC Participants | Percentage of Participants Who Underwent Metastasectomy | 6.2 Percentage of participants |
Secondary
Percentage of Participants With Clinical Benefit as Assessed Using RECIST v1.1
Clinical benefit was defined as having a confirmed CR, PR or stable disease (SD) for at least 24 weeks on study according to RECIST v1.1.CR: complete disappearance of all target lesions and non-target disease,with the exception of nodal disease.All nodes,both target and non-target, must decrease to normal (short axis \<10 mm).No new lesions.PR: \>=30% decrease under baseline of the sum of diameters of all target lesions.The short axis was used in the sum for target nodes,while the longest diameter was used in the sum for all other target lesions.No unequivocal progression of non-target disease.No new lesions.SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,taking as reference the smallest sum diameters while on study.PD:at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions,or presence of new lesions.
Time frame: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| mCRC Participants | Percentage of Participants With Clinical Benefit as Assessed Using RECIST v1.1 | 82.9 Percentage of participants |
Secondary
Percentage of Participants With Dose Modification of Capecitabine
Time frame: Baseline up to 1254 days
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| mCRC Participants | Percentage of Participants With Dose Modification of Capecitabine | 85.6 Percentage of participants |
Secondary
Percentage of Participants With Overall Response as Assessed by Investigator Using RECIST v1.1
Overall response is defined as a complete response (CR) or a partial response (PR) as determined by the Investigator using RECIST v1.1 on 2 consecutive occasions at least 6 weeks apart. Participants were evaluated for tumor response per RECIST v1.1 and assessed by computed tomography (CT) or magnetic resonance imaging (MRI):CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (\<) 10 mm). No new lesions.PR was defined as greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time frame: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| mCRC Participants | Percentage of Participants With Overall Response as Assessed by Investigator Using RECIST v1.1 | 24.3 Percentage of participants |