Colorectal Neoplasms
Conditions
Brief summary
This open-label, prospective, single-arm, multicenter study will evaluate the relationship of the markers of inflammation and progression-free survival (PFS) in participants with previously untreated metastatic colorectal cancer. The study consists of two phases: Phase A treatment: oral capecitabine plus infusional oxaliplatin (XELOX) plus bevacizumab, or modified infusional 5-fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (mFOLFOX6) plus bevacizmab administered until first disease progression. Participants will then continue with Phase B treatment: infusional 5-FU, LV and irinotecan (FOLFIRI) plus bevacizumab until second disease progression. The anticipated time on study treatment is 4 years.
Interventions
DRUGOxaliplatin
Participants will receive oxaliplatin 85 milligrams per square meter (mg/m\^2) IV infusion on Day 1 of every 2 weeks cycle during alternative Phase A treatment or 130 mg/m\^2 on Day 1 of every 3 weeks cycle during Phase A treatment.
DRUGCapecitabine
Participants will receive capecitabine 1000 mg/m\^2 per oral (PO) twice daily on Days 1-14 of 3 weeks cycle during Phase A treatment.
DRUGBevacizumab
Participants will receive 7.5 mg/kg IV infusion on Day 1 every 3 weeks (Phase A treatment) or 5 mg/kg IV on Day 1 every 2 weeks (Alternative Phase A treatment and Phase B).
DRUGLeucovorin
Participants will receive leucovorin 400 mg/m\^2 IV on Day 1 every 2 weeks (Alternative Phase A treatment and Phase B). Investigators may elect to chose low dose of leucovorin (either 20 mg/m\^2 or 50 mg total dose).
DRUG5-Fluouracil
Participants will receive 5-fluouracil loading dose of 400 mg/m\^2 IV on Day 1 followed by 2400 mg/m\^2 continuous IV infusion over 46 hours Day 1 (Alternative Phase A treatment and Phase B).
DRUGIrinotecan
Participants will receive irinotecan 180 mg/m\^2 IV on Day 1 every 2 weeks during Phase B treatment.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For resected primary tumor participants, and participants with primary tumor in situ: * Previously untreated metastatic colorectal cancer and not a candidate for curative resection * World Health Organization (WHO) performance status of 0-1 * Life expectancy of greater than or equal to (\>/=) 3 months * Eligible for XELOX, mFOLFOX6, FOLFIRI and bevacizumab treatment in accordance with local standards of care and pharmaceutical benefits scheme guidelines Additional inclusion criteria for participants with primary tumor in situ: * Intact primary tumor of the colon or the rectum not requiring surgical intervention prior to study start * Minimal or asymptomatic primary tumor
Exclusion criteria
Resected primary tumor participants, and participants with primary tumor in situ: * Previous chemotherapy for metastatic colorectal cancer * Previous neoadjuvant or adjuvant chemotherapy less than 6 months prior to study start * Radiotherapy within 28 days prior to enrollment or not recovered from a radiotherapy * History of non-colorectal cancer (participants are eligible if disease-free for \>/=5 years and the risk of recurrence is deemed low) * Presence of active inflammatory bowel disease * History of gastrointestinal perforations * Peritoneal disease * History of significant bleeding event * Significant vascular disease * Peripheral arterial thrombosis or other thrombotic event within 6 months before study start Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio | Baseline up to disease progression, death or end of study (up to 4 years) | NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. PFS was defined as the time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (carcinoembryonic antigen \[CEA\]) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. The association between NLR (NLR less than or equal to \[≤\] 5 vs greater than \[\>\] 5) and PFS was reported as hazard ratio. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A | Baseline up to first disease progression, death or end of study (up to 4 years) | PFS until first progression was defined as the time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate PFS. |
| PFS Until Second Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase B | From the start of Phase B treatment to disease progression, death or end of study (up to 4 years) | PFS in Phase B (PFS-B) was defined as the time from the start of Phase B treatment to documentation of second disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate PFS. |
| Time to Failure of Strategy (TFS): Overall | Baseline up to disease progression, death or end of study (up to 4 years) | TFS was defined as time from the start of initial treatment to documentation of first disease progression without entering Phase B, or second disease progression having entered Phase B. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate TFS. |
| Duration of Disease Control (DDC) as Assessed by the Investigator Based on Routine Clinical Practice: Overall | Baseline up to disease progression, death or end of study (up to 4 years) | DDC was defined as PFS + PFS-B. In cases where a participant did not enter Phase B, then DDC was defined as PFS. PFS was defined as time from start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. PFS-B was time from start of Phase B treatment to documentation of second disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate DDC. |
| Survival Beyond First Disease Progression: Overall | Baseline until death or end of study (up to 4 years) | Survival beyond first progression was defined as the time from the date of first disease progression to death due to any cause. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate survival beyond first disease progression. |
| OS: Phase B | From the start of Phase B treatment death or end of study (up to 4 years) | Overall Survival in Phase B was defined as the time from the start of treatment in Phase B to death due to any cause. Kaplan-Meier methodology was used to estimate OS. |
| Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A | Baseline up to disease progression, death or end of study (up to 4 years) | Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment. |
| Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B | From the start of Phase B treatment to disease progression, death or end of study (up to 4 years) | Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment. |
| Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall | Baseline up to disease progression, death or end of study (up to 4 years) | Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment. |
| Percentage of Participants Who Underwent Liver Resection: Overall | Baseline up to disease progression, death or end of study (up to 4 years) | The results include percentage of participants who underwent potentially curative liver resection. |
| Overall Survival (OS) From the Start of Treatment to Study Completion: Overall | Baseline until death or end of study (up to 4 years) | OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. Kaplan-Meier methodology was used to estimate OS. |
| Association Between NLR Normalization (First NLR Post-Baseline ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio | Baseline up to disease progression, death or end of study (up to 4 years) | NLR was calculated from laboratory values as ratio of Neutrophils to Lymphocytes. NLR normalization was assessed by adding first post-baseline measurement of NLR to the primary model. This is equivalent to testing whether first change in NLR is significantly associated with outcome. PFS was defined as time from start of initial treatment to documentation of first disease progression or death from any cause. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was defined as: an unequivocal and clinically meaningful increase in size of known tumors, appearance of ≥1 new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration.The association between NLR normalization (first NLR post-baseline ≤5 vs \>5) and PFS was reported as hazard ratio. |
| Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio | Baseline up to disease progression, death or end of study (up to 4 years) | NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. Longitudinal NLR was assessed by treating the NLR measurements taken over the time-course of treatment as a time-dependent covariate. PFS was defined as time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as: an unequivocal and clinically meaningful increase in size of known tumors, appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. The association between longitudinal NLR (longitudinal NLR ≤5 vs N\>5) and PFS was reported as hazard ratio. |
| Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio | Baseline up to death or end of study (up to 4 years) | NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. Longitudinal NLR was assessed by treating the NLR measurements taken over the time-course of treatment as a time-dependent covariate. OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. The association between longitudinal NLR (longitudinal NLR ≤5 vs NLR \>5) and OS was reported as hazard ratio. |
| European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Baseline, every 8-9 weeks thereafter, end of treatment (EOT) (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles] | EQ-5D is a standardized generic preference based health related quality of life instrument. It records how one's health is today and consists of a descriptive system. The descriptive system is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem\[s\] and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects' health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life. |
| EuroQol-5D Utility Score: Phase B | Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles] | EQ-5D is a standardized generic preference based health related quality of life instrument. It records how one's health is today and consists of a descriptive system. The descriptive system is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem\[s\] and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects' health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life. |
| Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles] | AQoL-8D provides a global utility score and comprised of 35 questions from which 8 dimensions (Independent Living, Life Satisfaction, Mental Health, Coping, Relationships, Self Worth, Pain, and Senses) are derived. Each of the 8 scales is calculated based on the answers to 3 questions. Each question is given an answer dependent utility score (0 \[worst\] to 1 \[best\]) and then these scores are combined using a multiplicative model to get the normalized scale score value, each scale ranging between 0.0 (representing death) and 1.0 (representing full health). |
| AQoL-8D Global Utility Score: Phase B | Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles] | AQoL-8D provides a global utility score and consists of 8 separately scored dimensions including Independent Living, Life Satisfaction, Mental Health, Coping, Relationships, Self Worth, Pain, and Senses. Each of the 8 scales is calculated based on the answers to 3 questions. Each question is given an answer dependent utility score (0 \[worst\] to 1 \[best\]) and then these scores are combined using a multiplicative model to get the normalized scale score value, each scale ranging between 0.0 (representing death) and 1.0 (representing full health). |
| Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles] | FACT-C is one part of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System, which comprehensively assesses the health-related QoL of cancer participants and participants with other chronic illnesses. It is composed of 27 items of the general version of the FACT-C as a general core QoL measure and has a disease-specific subscale containing 9 colorectal cancer-specific items. It consists of total 36 items, summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range from 0 to 28, emotional well-being (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL. |
| FACT-C Score: Phase B | Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles] | FACT-C is one part of the FACIT Measurement System, which comprehensively assesses the health-related QoL of cancer participants and participants with other chronic illnesses. It is composed of 27 items of the general version of the FACT-C as a general core QoL measure and has a disease-specific subscale containing 9 colorectal cancer-specific items. It consists of total 36 items, summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range from 0 to 28, emotional well-being (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL. |
| Association Between NLR (NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio | Baseline up to disease progression, death or end of study (up to 4 years) | NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. The association between NLR (NLR ≤ 5 vs \> 5) and OS was reported as hazard ratio. |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab: Phase A and Phase B The trial consisted of 2 phases of treatment. Phase A: Participants received bevacizumab 7.5 mg/kg intravenously (IV) on Day 1 every 3 weeks in combination with XELOX (oral capecitabine 1000 mg/m\^2 twice daily Days 1-14, oxaliplatin 130 mg/m\^2 IV Day 1) or bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with mFOLFOX6 (oxaliplatin 85 mg/m\^2 IV Day 1, leucovorin 400 mg/m\^2 IV Day 1, 5-fluouracil 400 mg/m\^2 IV loading dose then 2400 mg/m\^2 continuous IV infusion over 46 hours Day 1) until first disease progression or occurrence of unmanageable toxicity. Phase B: Upon documented first disease progression, participants continued receiving bevacizumab 5 mg/kg IV on Day 1 every 2 weeks in combination with FOLFIRI (irinotecan 180 mg/m\^2 IV Day 1, leucovorin and 5-fluouracil \[same regimen as of mFOLFOX6\]) until second disease progression or occurrence of unmanageable toxicity. Phase B treatment had to commence within 4 weeks of the date of documented first disease progression. | 128 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase A | Adverse Event | 28 |
| Phase A | Death | 5 |
| Phase A | Lost to Follow-up | 1 |
| Phase A | Other | 14 |
| Phase A | Physician Decision | 11 |
| Phase A | Still on therapy at end of study | 6 |
| Phase A | Withdrawal by Subject | 5 |
| Phase B | Adverse Event | 2 |
| Phase B | Other | 2 |
| Phase B | Physician Decision | 4 |
| Phase B | Still on therapy at end of study | 5 |
| Phase B | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Bevacizumab: Phase A and Phase B |
|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 11.66 |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 128 / 128 |
| serious Total, serious adverse events | 86 / 128 |
Outcome results
Primary
Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio
NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. PFS was defined as the time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (carcinoembryonic antigen \[CEA\]) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. The association between NLR (NLR less than or equal to \[≤\] 5 vs greater than \[\>\] 5) and PFS was reported as hazard ratio.
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Population: FAS population. Overall Number of Participants Analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Association Between Neutrophil to Lymphocyte Ratio (NLR) [NLR ≤5 Versus NLR >5] and Progression-Free Survival (PFS) as Assessed by Hazard Ratio | 1.4 hazard ratio |
p-value: 0.101Cox Proportional Hazards Model
Secondary
AQoL-8D Global Utility Score: Phase B
AQoL-8D provides a global utility score and consists of 8 separately scored dimensions including Independent Living, Life Satisfaction, Mental Health, Coping, Relationships, Self Worth, Pain, and Senses. Each of the 8 scales is calculated based on the answers to 3 questions. Each question is given an answer dependent utility score (0 \[worst\] to 1 \[best\]) and then these scores are combined using a multiplicative model to get the normalized scale score value, each scale ranging between 0.0 (representing death) and 1.0 (representing full health).
Time frame: Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Population: Phase B FAS population. Number Analyzed = participants who were evaluable at the specified time point for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Survival Follow-Up 4 (up to 4 years) | 0.981 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Baseline | 0.736 units on a scale | Standard Deviation 0.1943 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 2 (up to 4 years) | 0.773 units on a scale | Standard Deviation 0.1821 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 3 (up to 4 years) | 0.813 units on a scale | Standard Deviation 0.161 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 4 (up to 4 years) | 0.878 units on a scale | Standard Deviation 0.1154 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 5 (up to 4 years) | 0.808 units on a scale | Standard Deviation 0.163 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 6 (up to 4 years) | 0.809 units on a scale | Standard Deviation 0.1717 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 7 (up to 4 years) | 0.825 units on a scale | Standard Deviation 0.1682 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 8 (up to 4 years) | 0.910 units on a scale | Standard Deviation 0.1023 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 9 (up to 4 years) | 0.819 units on a scale | Standard Deviation 0.1986 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 10 (up to 4 years) | 0.856 units on a scale | Standard Deviation 0.1589 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 11 (up to 4 years) | 0.730 units on a scale | Standard Deviation 0.2906 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 12 (up to 4 years) | 0.960 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 13 (up to 4 years) | 0.965 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 14 (up to 4 years) | 0.958 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 15 (up to 4 years) | 0.967 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 16 (up to 4 years) | 0.942 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 17 (up to 4 years) | 0.927 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 18 (up to 4 years) | 0.931 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 19 (up to 4 years) | 0.866 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 20 (up to 4 years) | 0.887 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 21 (up to 4 years) | 0.940 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 22 (up to 4 years) | 0.919 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 23 (up to 4 years) | 0.937 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B Visit 24 (up to 4 years) | 0.950 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Phase B EOT Visit (up to 4 years) | 0.708 units on a scale | Standard Deviation 0.2229 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Survival Follow-Up 1 (up to 4 years) | 0.788 units on a scale | Standard Deviation 0.0895 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Survival Follow-Up 2 (up to 4 years) | 0.791 units on a scale | Standard Deviation 0.1829 |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Survival Follow-Up 3 (up to 4 years) | 0.989 units on a scale | — |
| Bevacizumab: Phase A and Phase B | AQoL-8D Global Utility Score: Phase B | Survival Follow-Up 6 (up to 4 years) | 0.875 units on a scale | — |
Secondary
Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A
AQoL-8D provides a global utility score and comprised of 35 questions from which 8 dimensions (Independent Living, Life Satisfaction, Mental Health, Coping, Relationships, Self Worth, Pain, and Senses) are derived. Each of the 8 scales is calculated based on the answers to 3 questions. Each question is given an answer dependent utility score (0 \[worst\] to 1 \[best\]) and then these scores are combined using a multiplicative model to get the normalized scale score value, each scale ranging between 0.0 (representing death) and 1.0 (representing full health).
Time frame: Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Population: FAS population. Number Analyzed = participants who were evaluable at the specified time point for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Baseline | 0.747 units on a scale | Standard Deviation 0.1819 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 2 (Weeks 8-9) | 0.760 units on a scale | Standard Deviation 0.171 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 3 (Weeks 16-17) | 0.767 units on a scale | Standard Deviation 0.1691 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 4 (Weeks 24-25) | 0.796 units on a scale | Standard Deviation 0.165 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 5 (Weeks 32-33) | 0.800 units on a scale | Standard Deviation 0.1762 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 6 (Weeks 40-41) | 0.831 units on a scale | Standard Deviation 0.1578 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 7 (Weeks 48-49) | 0.818 units on a scale | Standard Deviation 0.1455 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 8 (Weeks 56-57) | 0.851 units on a scale | Standard Deviation 0.1043 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 9 (Weeks 64-65) | 0.822 units on a scale | Standard Deviation 0.1304 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 10 (Weeks 72-73) | 0.827 units on a scale | Standard Deviation 0.1426 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 11 (Weeks 80-81) | 0.839 units on a scale | Standard Deviation 0.1272 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 12 (Weeks 88-89) | 0.856 units on a scale | Standard Deviation 0.1295 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 13 (Weeks 96-97) | 0.831 units on a scale | Standard Deviation 0.1482 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 14 (Weeks 104-105) | 0.815 units on a scale | Standard Deviation 0.1788 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 15 (Weeks 112-113) | 0.871 units on a scale | Standard Deviation 0.0877 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 16 (Weeks 120-121) | 0.869 units on a scale | Standard Deviation 0.1428 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 17 (Weeks 128-129) | 0.859 units on a scale | Standard Deviation 0.143 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 18 (Weeks 136-137) | 0.880 units on a scale | Standard Deviation 0.1048 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 19 (Weeks 144-145) | 0.915 units on a scale | Standard Deviation 0.0883 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 20 (Weeks 152-153) | 0.864 units on a scale | Standard Deviation 0.1266 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 21 (Weeks 160-161) | 0.806 units on a scale | Standard Deviation 0.1422 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 22 (Weeks 168-169) | 0.811 units on a scale | Standard Deviation 0.2238 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A Visit 23 (Weeks 176-177) | 0.709 units on a scale | Standard Deviation 0.3336 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Phase A EOT Visit (up to 4 years) | 0.739 units on a scale | Standard Deviation 0.1882 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Survival Follow-Up 1 (up to 4 years) | 0.718 units on a scale | Standard Deviation 0.16 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Survival Follow-Up 2 (up to 4 years) | 0.792 units on a scale | Standard Deviation 0.1977 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Survival Follow-Up 3 (up to 4 years) | 0.696 units on a scale | Standard Deviation 0.1684 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Survival Follow-Up 4 (up to 4 years) | 0.620 units on a scale | — |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Survival Follow-Up 5 (up to 4 years) | 0.800 units on a scale | — |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Survival Follow-Up 6 (up to 4 years) | 0.810 units on a scale | Standard Deviation 0.0531 |
| Bevacizumab: Phase A and Phase B | Assessment of Quality of Life - Eight Dimensions (AQoL-8D) Global Utility Score: Phase A | Survival Follow-Up 7 (up to 4 years) | 0.874 units on a scale | — |
Secondary
Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. Longitudinal NLR was assessed by treating the NLR measurements taken over the time-course of treatment as a time-dependent covariate. OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. The association between longitudinal NLR (longitudinal NLR ≤5 vs NLR \>5) and OS was reported as hazard ratio.
Time frame: Baseline up to death or end of study (up to 4 years)
Population: FAS population. Overall Number of Participants Analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio | 2.2 hazard ratio |
p-value: 0.016Cox Proportional Hazards Model
Secondary
Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. Longitudinal NLR was assessed by treating the NLR measurements taken over the time-course of treatment as a time-dependent covariate. PFS was defined as time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as: an unequivocal and clinically meaningful increase in size of known tumors, appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. The association between longitudinal NLR (longitudinal NLR ≤5 vs N\>5) and PFS was reported as hazard ratio.
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Population: FAS population. Overall Number of Participants Analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Association Between Longitudinal NLR (Longitudinal NLR ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio | 1.3 hazard ratio |
p-value: 0.188Cox Proportional Hazards Model
Secondary
Association Between NLR (NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio
NLR was calculated from the laboratory values as the ratio of Neutrophils to Lymphocytes. OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. The association between NLR (NLR ≤ 5 vs \> 5) and OS was reported as hazard ratio.
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Population: FAS population. Overall Number of Participants Analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Association Between NLR (NLR ≤5 Versus NLR >5) and OS as Assessed by Hazard Ratio | 1.6 hazard ratio |
p-value: 0.052Cox Proportional Hazards Model
Secondary
Association Between NLR Normalization (First NLR Post-Baseline ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio
NLR was calculated from laboratory values as ratio of Neutrophils to Lymphocytes. NLR normalization was assessed by adding first post-baseline measurement of NLR to the primary model. This is equivalent to testing whether first change in NLR is significantly associated with outcome. PFS was defined as time from start of initial treatment to documentation of first disease progression or death from any cause. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was defined as: an unequivocal and clinically meaningful increase in size of known tumors, appearance of ≥1 new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration.The association between NLR normalization (first NLR post-baseline ≤5 vs \>5) and PFS was reported as hazard ratio.
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Population: FAS population. Overall Number of Participants Analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Association Between NLR Normalization (First NLR Post-Baseline ≤5 Versus NLR >5) and PFS as Assessed by Hazard Ratio | 0.9 hazard ratio |
p-value: 0.797Cox Proportional Hazards Model
Secondary
Duration of Disease Control (DDC) as Assessed by the Investigator Based on Routine Clinical Practice: Overall
DDC was defined as PFS + PFS-B. In cases where a participant did not enter Phase B, then DDC was defined as PFS. PFS was defined as time from start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. PFS-B was time from start of Phase B treatment to documentation of second disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate DDC.
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Population: FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Duration of Disease Control (DDC) as Assessed by the Investigator Based on Routine Clinical Practice: Overall | 14.0 months |
Secondary
European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A
EQ-5D is a standardized generic preference based health related quality of life instrument. It records how one's health is today and consists of a descriptive system. The descriptive system is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem\[s\] and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects' health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life.
Time frame: Baseline, every 8-9 weeks thereafter, end of treatment (EOT) (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Population: FAS population. Number Analyzed = participants who were evaluable at the specified time point for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Baseline | 0.830 units on a scale | Standard Deviation 0.159 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 2 (Weeks 8-9) | 0.857 units on a scale | Standard Deviation 0.1392 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 3 (Weeks 16-17) | 0.865 units on a scale | Standard Deviation 0.1074 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 4 (Weeks 24-25) | 0.853 units on a scale | Standard Deviation 0.1206 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 5 (Weeks 32-33) | 0.869 units on a scale | Standard Deviation 0.1381 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 6 (Weeks 40-41) | 0.892 units on a scale | Standard Deviation 0.1013 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 7 (Weeks 48-49) | 0.872 units on a scale | Standard Deviation 0.1332 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 8 (Weeks 56-57) | 0.881 units on a scale | Standard Deviation 0.1058 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 9 (Weeks 64-65) | 0.894 units on a scale | Standard Deviation 0.1081 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 10 (Weeks 72-73) | 0.843 units on a scale | Standard Deviation 0.1466 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 11 (Weeks 80-81) | 0.898 units on a scale | Standard Deviation 0.0952 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 12 (Weeks 88-89) | 0.915 units on a scale | Standard Deviation 0.1033 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 13 (Weeks 96-97) | 0.844 units on a scale | Standard Deviation 0.1463 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 14 (Weeks 104-105) | 0.899 units on a scale | Standard Deviation 0.1398 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 15 (Weeks 112-113) | 0.878 units on a scale | Standard Deviation 0.0861 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 16 (Weeks 120-121) | 0.899 units on a scale | Standard Deviation 0.0852 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 17 (Weeks 128-129) | 0.873 units on a scale | Standard Deviation 0.1734 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 18 (Weeks 136-137) | 0.909 units on a scale | Standard Deviation 0.0876 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 19 (Weeks 144-145) | 0.947 units on a scale | Standard Deviation 0.0914 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 20 (Weeks 152-153) | 0.852 units on a scale | Standard Deviation 0.0718 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 21 (Weeks 160-161) | 0.933 units on a scale | Standard Deviation 0.1156 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 22 (Weeks 168-169) | 0.813 units on a scale | Standard Deviation 0.0193 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A Visit 23 (Weeks 176-177) | 0.900 units on a scale | Standard Deviation 0.1416 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Phase A EOT Visit (up to 4 years) | 0.817 units on a scale | Standard Deviation 0.1423 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Survival Follow-Up 1 (up to 4 years) | 0.768 units on a scale | Standard Deviation 0.1414 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Survival Follow-Up 2 (up to 4 years) | 0.901 units on a scale | Standard Deviation 0.086 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Survival Follow-Up 3 (up to 4 years) | 0.819 units on a scale | Standard Deviation 0.0583 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Survival Follow-Up 4 (up to 4 years) | 0.843 units on a scale | — |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Survival Follow-Up 5 (up to 4 years) | 1.000 units on a scale | — |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Survival Follow-Up 6 (up to 4 years) | 0.835 units on a scale | Standard Deviation 0.0229 |
| Bevacizumab: Phase A and Phase B | European Quality of Life 5-Dimension (EuroQol-5D) Utility Score: Phase A | Survival Follow-Up 7 (up to 4 years) | 0.816 units on a scale | — |
Secondary
EuroQol-5D Utility Score: Phase B
EQ-5D is a standardized generic preference based health related quality of life instrument. It records how one's health is today and consists of a descriptive system. The descriptive system is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension on the EQ-5D involves a 3-point response scale which indicates the level of impairment (level 1 = no problem; level 2 = some or moderate problem\[s\] and level 3 = unable, or extreme problems). Level of problem reported in each EQ-5D dimension determines a unique health state which is converted into a weighted health state index by applying scores from EQ-5D preference weights elicited from general population samples. This generates a unique description of the subjects' health status, which is valued between 0 (representing death) and 1 (representing perfect health). Higher the score, the better the quality of life.
Time frame: Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Population: Phase B FAS population. Number Analyzed = participants who were evaluable at the specified time point for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Baseline | 0.814 units on a scale | Standard Deviation 0.1566 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 2 (up to 4 years) | 0.859 units on a scale | Standard Deviation 0.1376 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 3 (up to 4 years) | 0.894 units on a scale | Standard Deviation 0.1108 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 4 (up to 4 years) | 0.897 units on a scale | Standard Deviation 0.1012 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 5 (up to 4 years) | 0.866 units on a scale | Standard Deviation 0.1299 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 6 (up to 4 years) | 0.837 units on a scale | Standard Deviation 0.171 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 7 (up to 4 years) | 0.876 units on a scale | Standard Deviation 0.0986 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 8 (up to 4 years) | 0.874 units on a scale | Standard Deviation 0.1141 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 9 (up to 4 years) | 0.908 units on a scale | Standard Deviation 0.1299 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 10 (up to 4 years) | 0.811 units on a scale | Standard Deviation 0.0466 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 11 (up to 4 years) | 0.806 units on a scale | Standard Deviation 0.0539 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 12 (up to 4 years) | 0.844 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 13 (up to 4 years) | 1.000 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 14 (up to 4 years) | 1.000 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 15 (up to 4 years) | 0.844 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 16 (up to 4 years) | 0.833 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 17 (up to 4 years) | 0.844 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 18 (up to 4 years) | 0.833 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 19 (up to 4 years) | 0.827 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 20 (up to 4 years) | 0.816 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 21 (up to 4 years) | 0.844 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 22 (up to 4 years) | 0.844 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 23 (up to 4 years) | 0.827 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B Visit 24 (up to 4 years) | 0.844 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Phase B EOT Visit (up to 4 years) | 0.809 units on a scale | Standard Deviation 0.1585 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Survival Follow-Up 1 (up to 4 years) | 0.740 units on a scale | Standard Deviation 0.1035 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Survival Follow-Up 2 (up to 4 years) | 0.772 units on a scale | Standard Deviation 0.0782 |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Survival Follow-Up 3 (up to 4 years) | 0.827 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Survival Follow-Up 4 (up to 4 years) | 0.827 units on a scale | — |
| Bevacizumab: Phase A and Phase B | EuroQol-5D Utility Score: Phase B | Survival Follow-Up 6 (up to 4 years) | 1.000 units on a scale | — |
Secondary
FACT-C Score: Phase B
FACT-C is one part of the FACIT Measurement System, which comprehensively assesses the health-related QoL of cancer participants and participants with other chronic illnesses. It is composed of 27 items of the general version of the FACT-C as a general core QoL measure and has a disease-specific subscale containing 9 colorectal cancer-specific items. It consists of total 36 items, summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range from 0 to 28, emotional well-being (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL.
Time frame: Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Population: Phase B FAS population. Number Analyzed = participants who were evaluable at the specified time point for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Baseline | 103.47 units on a scale | Standard Deviation 18.284 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 2 (up to 4 years) | 108.71 units on a scale | Standard Deviation 17.387 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 3 (up to 4 years) | 108.19 units on a scale | Standard Deviation 16.541 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 4 (up to 4 years) | 114.89 units on a scale | Standard Deviation 14.467 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 5 (up to 4 years) | 110.60 units on a scale | Standard Deviation 15.592 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 6 (up to 4 years) | 111.28 units on a scale | Standard Deviation 14.121 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 7 (up to 4 years) | 114.78 units on a scale | Standard Deviation 12.64 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 8 (up to 4 years) | 120.39 units on a scale | Standard Deviation 9.007 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 9 (up to 4 years) | 108.08 units on a scale | Standard Deviation 18.267 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 10 (up to 4 years) | 110.50 units on a scale | Standard Deviation 17.678 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 11 (up to 4 years) | 109.33 units on a scale | Standard Deviation 19.328 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 12 (up to 4 years) | 125.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 13 (up to 4 years) | 119.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 14 (up to 4 years) | 117.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 15 (up to 4 years) | 126.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 16 (up to 4 years) | 123.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 17 (up to 4 years) | 127.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 18 (up to 4 years) | 126.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 19 (up to 4 years) | 127.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 20 (up to 4 years) | 126.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 21 (up to 4 years) | 123.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 22 (up to 4 years) | 124.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 23 (up to 4 years) | 126.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B Visit 24 (up to 4 years) | 130.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Phase B EOT Visit (up to 4 years) | 101.67 units on a scale | Standard Deviation 19.023 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Survival Follow-Up 1 (up to 4 years) | 98.72 units on a scale | Standard Deviation 20.024 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Survival Follow-Up 2 (up to 4 years) | 102.50 units on a scale | Standard Deviation 17.705 |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Survival Follow-Up 3 (up to 4 years) | 126.33 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Survival Follow-Up 4 (up to 4 years) | 125.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | FACT-C Score: Phase B | Survival Follow-Up 6 (up to 4 years) | 124.67 units on a scale | — |
Secondary
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A
FACT-C is one part of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System, which comprehensively assesses the health-related QoL of cancer participants and participants with other chronic illnesses. It is composed of 27 items of the general version of the FACT-C as a general core QoL measure and has a disease-specific subscale containing 9 colorectal cancer-specific items. It consists of total 36 items, summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range from 0 to 28, emotional well-being (6 items) range from 0 to 24, colorectal cancer subscale (9 items) range from 0 to 36; higher subscale score=better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score range: 0 to 144. High scale score represents a better QoL.
Time frame: Baseline, every 8-9 weeks thereafter, EOT (30 days after disease progression [up to 4 years]), survival follow-up 12-weekly visits (up to 4 years) [Detailed time points are presented in the category titles]
Population: FAS population. Number Analyzed = participants who were evaluable at the specified time point for this outcome.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Baseline | 103.84 units on a scale | Standard Deviation 16.615 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 2 (Weeks 8-9) | 103.33 units on a scale | Standard Deviation 16.065 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 3 (Weeks 16-17) | 106.34 units on a scale | Standard Deviation 15.318 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 4 (Weeks 24-25) | 109.66 units on a scale | Standard Deviation 15.038 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 5 (Weeks 32-33) | 109.39 units on a scale | Standard Deviation 16.727 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 6 (Weeks 40-41) | 111.30 units on a scale | Standard Deviation 16.42 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 7 (Weeks 48-49) | 111.40 units on a scale | Standard Deviation 13.506 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 8 (Weeks 56-57) | 113.51 units on a scale | Standard Deviation 10.777 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 9 (Weeks 64-65) | 113.92 units on a scale | Standard Deviation 12.239 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 10 (Weeks 72-73) | 115.11 units on a scale | Standard Deviation 15.473 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 11 (Weeks 80-81) | 114.00 units on a scale | Standard Deviation 13.23 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 12 (Weeks 88-89) | 115.99 units on a scale | Standard Deviation 12.844 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 13 (Weeks 96-97) | 113.54 units on a scale | Standard Deviation 12.298 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 14 (Weeks 104-105) | 112.36 units on a scale | Standard Deviation 15.443 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 15 (Weeks 112-113) | 119.48 units on a scale | Standard Deviation 11.542 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 16 (Weeks 120-121) | 116.38 units on a scale | Standard Deviation 15.214 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 17 (Weeks 128-129) | 113.69 units on a scale | Standard Deviation 17.816 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 18 (Weeks 136-137) | 112.94 units on a scale | Standard Deviation 16.931 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 19 (Weeks 144-145) | 117.55 units on a scale | Standard Deviation 10.397 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 20 (Weeks 152-153) | 115.86 units on a scale | Standard Deviation 13.12 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 21 (Weeks 160-161) | 106.00 units on a scale | Standard Deviation 20.664 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 22 (Weeks 168-169) | 112.00 units on a scale | Standard Deviation 26.87 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A Visit 23 (Weeks 176-177) | 105.00 units on a scale | Standard Deviation 36.77 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Phase A EOT Visit (up to 4 years) | 103.94 units on a scale | Standard Deviation 17.429 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Survival Follow-Up 1 (up to 4 years) | 102.89 units on a scale | Standard Deviation 18.086 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Survival Follow-Up 2 (up to 4 years) | 104.00 units on a scale | Standard Deviation 8.047 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Survival Follow-Up 3 (up to 4 years) | 105.50 units on a scale | Standard Deviation 10.607 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Survival Follow-Up 4 (up to 4 years) | 109.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Survival Follow-Up 5 (up to 4 years) | 119.00 units on a scale | — |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Survival Follow-Up 6 (up to 4 years) | 103.61 units on a scale | Standard Deviation 4.945 |
| Bevacizumab: Phase A and Phase B | Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Score: Phase A | Survival Follow-Up 7 (up to 4 years) | 115.00 units on a scale | — |
Secondary
OS: Phase B
Overall Survival in Phase B was defined as the time from the start of treatment in Phase B to death due to any cause. Kaplan-Meier methodology was used to estimate OS.
Time frame: From the start of Phase B treatment death or end of study (up to 4 years)
Population: Phase B FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | OS: Phase B | 14.9 months |
Secondary
Overall Survival (OS) From the Start of Treatment to Study Completion: Overall
OS was defined as the time from the start of initial treatment to the date of death, regardless of the cause of death. Kaplan-Meier methodology was used to estimate OS.
Time frame: Baseline until death or end of study (up to 4 years)
Population: FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Overall Survival (OS) From the Start of Treatment to Study Completion: Overall | 25.0 months |
Secondary
Percentage of Participants Who Underwent Liver Resection: Overall
The results include percentage of participants who underwent potentially curative liver resection.
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Population: FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Percentage of Participants Who Underwent Liver Resection: Overall | 1.6 percentage of participants |
Secondary
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall
Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment.
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Population: FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab: Phase A and Phase B | Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall | Complete response | 3.1 percentage of participants |
| Bevacizumab: Phase A and Phase B | Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Overall | Partial response | 8.6 percentage of participants |
Secondary
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment.
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Population: FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab: Phase A and Phase B | Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A | Complete response | 3.1 percentage of participants |
| Bevacizumab: Phase A and Phase B | Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase A | Partial response | 8.6 percentage of participants |
Secondary
Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
Percentage of participants with best overall response of confirmed complete response or partial response based on the investigator assessment of the response as per routine clinical practice was reported. The confirmation of response must be no less than 4 weeks after initial assessment.
Time frame: From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
Population: Phase B FAS population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab: Phase A and Phase B | Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B | Complete response | 0 percentage of participants |
| Bevacizumab: Phase A and Phase B | Percentage of Participants With Confirmed Complete or Partial Response as Assessed by the Investigator Based on Routine Clinical Practice: Phase B | Partial response | 0 percentage of participants |
Secondary
PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A
PFS until first progression was defined as the time from the start of initial treatment to documentation of first disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate PFS.
Time frame: Baseline up to first disease progression, death or end of study (up to 4 years)
Population: FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | PFS Until First Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase A | 9.2 months |
Secondary
PFS Until Second Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase B
PFS in Phase B (PFS-B) was defined as the time from the start of Phase B treatment to documentation of second disease progression or death from any cause, whichever occurred first. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate PFS.
Time frame: From the start of Phase B treatment to disease progression, death or end of study (up to 4 years)
Population: Phase B FAS population included participants who received at least 1 dose of bevacizumab in Phase B.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | PFS Until Second Disease Progression as Assessed by the Investigator Based on Routine Clinical Practice: Phase B | 6.7 months |
Secondary
Survival Beyond First Disease Progression: Overall
Survival beyond first progression was defined as the time from the date of first disease progression to death due to any cause. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate survival beyond first disease progression.
Time frame: Baseline until death or end of study (up to 4 years)
Population: FAS population. Overall Number of Participants Analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Survival Beyond First Disease Progression: Overall | 12.6 months |
Secondary
Time to Failure of Strategy (TFS): Overall
TFS was defined as time from the start of initial treatment to documentation of first disease progression without entering Phase B, or second disease progression having entered Phase B. Disease progression was determined according to standard practice based on radiological, biochemical (CEA) or clinical factors. Determination of disease progression was to be unequivocal and was defined as any of the following: an unequivocal and clinically meaningful increase in the size of known tumors, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, elevated CEA accompanied by other radiological or clinical evidence of progression, or symptomatic deterioration. Kaplan-Meier methodology was used to estimate TFS.
Time frame: Baseline up to disease progression, death or end of study (up to 4 years)
Population: FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab: Phase A and Phase B | Time to Failure of Strategy (TFS): Overall | 14.8 months |