Glioblastoma Multiforme
Conditions
Brief summary
This 2 arm study will compare the effect of Avastin + irinotecan versus temozolomide, in combination with conventional involved field radiotherapy, in patients with newly diagnosed glioblastoma and a non-methylated MGMT promoter. Patients will be randomized 3:1 to receive Avastin 10mg/kg iv every 2 weeks + irinotecan 125mg/m2 iv every 2 weeks, or temozolomide 75mg/m2 po daily during radiotherapy followed by 6 cycles of temozolomide 150-200mg/m2 po daily on days 1-5 of each 4 week cycle. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
Interventions
DRUGbevacizumab [Avastin]
10mg/kg iv every 2 weeks
DRUGirinotecan
125mg/m2 iv every 2 weeks
DRUGtemozolomide
75mg/m2 po daily during radiotherapy, followed by 150-200mg/m2/day po on days 1-5 of each 6x4 week cycle of adjuvant therapy
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* adult patients, 18-70 years of age; * glioblastoma, confirmed histologically; * no previous chemotherapy or radiotherapy for glioblastoma; * non-methylated MGMT promoter in the tumor.
Exclusion criteria
* prior systemic treatment for glioblastoma multiforme; * prior treatment with Avastin; * significant cardiovascular disease; * other active malignant disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months | 6 months | Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first. Progression was defined as 25 percent (%) increase in size of enhancing tumor or any new tumor on gadolinium contrast agent magnetic resonance imaging (Gd-MRI) scans, or neurologically worse, and steroids stable or increased. Percentage of participants achieving PFS without disease progression or death was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From baseline until death (up to 4.5 years) | Overall survival was defined as the time from randomization to death from any cause. OS was estimated using Kaplan-Meier method. |
| Percentage of Participants Who Discontinued | From baseline until death (up to 4.5 years) | Discontinuation was defined as the percentage of participants who permanently discontinued treatment in either treatment arm. Percentage of participant with individual discontinuation reason are reported. CNS: central nervous system; CTCAE: Common Terminology Criteria for Adverse Events . Other reason refers to any other reason than the specified ones. |
| Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | 4 week after radiotherapy (RT) (up to Week 4), >4 Week after RT (up to Week 8) and Month 6 | BOR was defined as the best response observed for a participant during assessment. Number of participants who had BOR as CR and number of participants who had BOR as CR or PR were reported. Complete response was defined as disappearance of all enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, off steroids, and neurologically stable or improved. Partial response was defined as 50% reduction in size of enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, steroids stable or reduced, and neurologically stable or improved. |
| Percentage of Participants With Response on FLAIR Imaging | At screening, Baseline, Month 6 and Therapy Discontinuation (Up to 4.5 years) | FLAIR lesions were determined as stable, progressive or decreased. FLAIR lesions was determined as progressive only if they were not be attributed to causes apart from tumor infiltration (sequelae of radiation therapy, demyelination, ischemia, infection, seizures, or other treatment effects). Percentage of participants are based on ITT population. Dis.=Discontinuation. |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Baseline, Post-Baseline (up to Month 30) | The EORTC QLQ-C30 incorporates: 5 functional scales (physical, role, cognitive, emotional, and social); 9 symptom scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties); and a global health and quality-of-life scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; higher score for Global Qol/functional scales=better level of functioning or a higher score for symptom scale=greater degree of symptoms. The change in global health status was determined to be the difference in values at baseline and each specific visit. The term ''baseline'' refers to the time of randomization to the maintenance phase. |
| Progression-Free Survival (PFS) | From baseline to the end of the study (up to 4.5 years) | Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first. Progression was defined as 25% increase in size of enhancing tumor or any new tumor on Gd-MRI scans, or neurologically worse, and steroids stable or increased. PFS was estimated using Kaplan-Meier method. |
| Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Baseline, Post-Baseline (up to Month 30) | The MMSE briefly measures orientation to time and place, immediate recall, short-term verbal memory, calculation, language and construct ability. Each area tested had a designated point value, the total score can range from 0 to 30, with a higher score indicating better function. |
| Change From Baseline for Karnofsky Performance Status (KPS) Score at Baseline, Post-Baseline (up to Month 30) | Baseline, Post-Baseline (up to Month 30) | KPS is an 11-level score (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100) which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks. Deterioration in KPS was defined as decrease of 20 or more points in KPS score. |
| Percentage of Participants Who Received Corticosteroid for Glioblastoma | From baseline to Month 6 | Participants used corticosteroids for the glioblastoma condition. Corticosteroids included dexamethasone, methylprednisone, fortecortin, hydrocortisone, urbason, and prednisolone. |
| Time to Treatment Failure | From baseline until end of study (up to 4.5 years) | — |
| Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Baseline, Post-Baseline (up to Month 30) | EORTC QLQ-BN20 consisted of 20 items assessing visual disorders, motor dysfunction, communication deficit, various disease symptoms (e.g. headaches and seizures), treatment toxicities (e.g. hair loss) and future uncertainty. All of the 20 items are rated on a 4 point Likert scale from 1=not at all, 2=a little, 3=quite a bit and 4=very much, and were linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + Irinotecan In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gray (Gy) given 5 fractions per week for 6 to 7 weeks and intravenous infusion (IV) of bevacizumab (BEV) 10 milligrams per kilogram (mg/kg) body weight every 14 ± 2 days starting during the first week to the last week of radiotherapy. Participants then entered the Maintenance Phase where they received BEV 10 mg/kg body weight and IV irinotecan (IRI) 125 milligrams per square meter (mg/m\^2) body surface area (BSA) or 340 mg/m\^2 BSA in participants not receiving enzyme-inducing antiepileptic drugs (EIAEDs) or receiving EIAEDs, respectively for every 14± 2 days until progressive disease (PD) or for a maximum treatment period of 2 years after inclusion of the last participant. | 122 |
| Temozolomide In the Concurrent Phase participants received radiotherapy in daily fractions of 1.8 to 2 Gy given 5 fractions per week for 6 to 7 week and temozolomide (TMZ) capsule 75 mg/m\^2 BSA daily from the first day to the last day of radiotherapy . There was a 4 week treatment break. Participants then entered the Maintenance Phase where they received six 28-day cycle of TMZ 150 to 200 mg/m\^2 BSA daily in the first 5 days of each cycle until PD or for a maximum treatment period of 2 years after inclusion of the last participant. Only participants with progressive disease during or after TMZ therapy could receive bevacizumab (BEV)/irinotecan (IRI) or BEV monotherapy as optional second-line study therapy at the discretion of the investigator, if eligible. | 60 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 102 | 51 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 3 | 4 |
| Overall Study | Regular | 10 | 3 |
| Overall Study | Severe protocol deviation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 0 |
Baseline characteristics
| Characteristic | Bevacizumab + Irinotecan | Temozolomide | Total |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 10.17 | 56.4 years STANDARD_DEVIATION 10.84 | 55.7 years STANDARD_DEVIATION 10.37 |
| Sex: Female, Male Female | 39 Participants | 21 Participants | 60 Participants |
| Sex: Female, Male Male | 83 Participants | 39 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 107 / 119 | 37 / 55 |
| serious Total, serious adverse events | 86 / 119 | 46 / 55 |
Outcome results
Primary
Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months
Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first. Progression was defined as 25 percent (%) increase in size of enhancing tumor or any new tumor on gadolinium contrast agent magnetic resonance imaging (Gd-MRI) scans, or neurologically worse, and steroids stable or increased. Percentage of participants achieving PFS without disease progression or death was reported.
Time frame: 6 months
Population: Intent-to-treat (ITT) population included participants randomized for whom it cannot be ruled out, that they took study medication at least once and where primary variable was measured at least once under study medication. Data were analyzed according to the treatment randomized (as randomized).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Irinotecan | Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months | 79.31 percentage of participants |
| Temozolomide | Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months | 42.59 percentage of participants |
p-value: <0.0001Chi-squared
Secondary
Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30)
EORTC QLQ-BN20 consisted of 20 items assessing visual disorders, motor dysfunction, communication deficit, various disease symptoms (e.g. headaches and seizures), treatment toxicities (e.g. hair loss) and future uncertainty. All of the 20 items are rated on a 4 point Likert scale from 1=not at all, 2=a little, 3=quite a bit and 4=very much, and were linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
Time frame: Baseline, Post-Baseline (up to Month 30)
Population: ITT population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Bevacizumab + Irinotecan | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Future uncertainty | -5.2779 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Headaches | 4.3905 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Itchy skin | 5.4882 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Drowsines | 11.7204 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Motor dysfunction | 5.4416 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Hair loss | 11.9235 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Weakness of legs | 8.9586 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Communication deficit | 4.7440 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Bladder control | 1.5020 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Visual disorder | -2.0869 units on a scale |
| Temozolomide | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Bladder control | 1.9710 units on a scale |
| Temozolomide | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Visual disorder | -3.202 units on a scale |
| Temozolomide | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Itchy skin | 6.4690 units on a scale |
| Temozolomide | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Future uncertainty | -8.5478 units on a scale |
| Temozolomide | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Motor dysfunction | 6.5429 units on a scale |
| Temozolomide | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Communication deficit | 4.6431 units on a scale |
| Temozolomide | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Headaches | -3.9389 units on a scale |
| Temozolomide | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Drowsines | 8.2805 units on a scale |
| Temozolomide | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Hair loss | 7.3328 units on a scale |
| Temozolomide | Change From Baseline for EORTC QLQ Brain Neoplasm 20 (BN20) at Baseline, Post-Baseline (up to Month 30) | Weakness of legs | 7.9245 units on a scale |
Comparison: Hair loss. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.238395% CI: [-12.2279, 3.0464]ANOVA
Comparison: Future uncertainty. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.361395% CI: [-10.2983, 3.7585]ANOVA
Comparison: Visual disorder. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.614695% CI: [-5.4654, 3.2336]ANOVA
Comparison: Motor dysfunction. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.68695% CI: [-4.2449, 6.4477]ANOVA
Comparison: Communication deficit. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.970695% CI: [-5.468, 5.2663]ANOVA
Comparison: Headaches. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.012495% CI: [-14.855, -1.8037]ANOVA
Comparison: Seizures. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.599795% CI: [-4.7654, 2.7545]ANOVA
Comparison: Drowsiness. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.345895% CI: [-10.6002, 3.7204]ANOVA
Comparison: Itchy skin. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.749195% CI: [-5.0373, 6.9988]ANOVA
Comparison: Weakness of legs. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.775595% CI: [-8.1508, 6.0827]ANOVA
Comparison: Bladder control. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.84195% CI: [-4.1211, 5.0591]ANOVA
Secondary
Change From Baseline for Karnofsky Performance Status (KPS) Score at Baseline, Post-Baseline (up to Month 30)
KPS is an 11-level score (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100) which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks. Deterioration in KPS was defined as decrease of 20 or more points in KPS score.
Time frame: Baseline, Post-Baseline (up to Month 30)
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Bevacizumab + Irinotecan | Change From Baseline for Karnofsky Performance Status (KPS) Score at Baseline, Post-Baseline (up to Month 30) | -3.3399 units on a scale |
| Temozolomide | Change From Baseline for Karnofsky Performance Status (KPS) Score at Baseline, Post-Baseline (up to Month 30) | -5.4909 units on a scale |
Comparison: KPS score. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.207895% CI: [-5.4983, 1.1963]ANOVA
Secondary
Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30)
The MMSE briefly measures orientation to time and place, immediate recall, short-term verbal memory, calculation, language and construct ability. Each area tested had a designated point value, the total score can range from 0 to 30, with a higher score indicating better function.
Time frame: Baseline, Post-Baseline (up to Month 30)
Population: ITT population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Bevacizumab + Irinotecan | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Repetitions required | -0.05763 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Short-term verbal memory | 0.2012 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Immediate recall | -0.00264 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Language and construct ability | -0.1254 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Calculations | -0.2153 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Total Score | -0.2871 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Orientation to time and place | -0.01771 units on a scale |
| Temozolomide | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Total Score | -0.5999 units on a scale |
| Temozolomide | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Orientation to time and place | -0.2110 units on a scale |
| Temozolomide | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Immediate recall | -0.03219 units on a scale |
| Temozolomide | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Repetitions required | 0.08530 units on a scale |
| Temozolomide | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Calculations | -0.2120 units on a scale |
| Temozolomide | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Short-term verbal memory | 0.1634 units on a scale |
| Temozolomide | Change From Baseline for Mini-Mental Status Examination (MMSE) at Baseline, Post-Baseline (up to Month 30) | Language and construct ability | -0.2057 units on a scale |
Comparison: Orientation to time and place. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.081795% CI: [-0.411, 0.02438]ANOVA
Comparison: Immediate recall. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.077395% CI: [-0.06234, 0.003241]ANOVA
Comparison: Repetitions required. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.260895% CI: [-0.1065, 0.3924]ANOVA
Comparison: Calculations. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.983695% CI: [-0.3092, 0.3158]ANOVA
Comparison: Short-term verbal memory. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.66195% CI: [-0.2071, 0.1315]ANOVA
Comparison: Language and construct ability. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.446495% CI: [-0.2875, 0.1268]ANOVA
Comparison: Total score. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.471795% CI: [-1.1658, 0.5402]ANOVA
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30)
The EORTC QLQ-C30 incorporates: 5 functional scales (physical, role, cognitive, emotional, and social); 9 symptom scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties); and a global health and quality-of-life scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; higher score for Global Qol/functional scales=better level of functioning or a higher score for symptom scale=greater degree of symptoms. The change in global health status was determined to be the difference in values at baseline and each specific visit. The term ''baseline'' refers to the time of randomization to the maintenance phase.
Time frame: Baseline, Post-Baseline (up to Month 30)
Population: ITT population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Social Functioning | -6.2324 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Pain | 10.6876 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Role Functioning | -0.7635 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Dyspnoea | 3.7134 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Global health Status /QoL (ql) | -3.1134 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Insomnia | -2.6266 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Cognitive Functioning | -2.0188 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Appetite loss | 13.7423 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Fatique | 5.5228 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Constipation | 8.0230 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Emotional Functioning | 2.2774 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Diarrhoea | 6.0230 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Nausea/Vomitting | 8.9557 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Financial Problems | 4.8435 units on a scale |
| Bevacizumab + Irinotecan | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Physical Functioning | -8.3513 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Financial Problems | 2.1140 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Physical Functioning | -6.2511 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Role Functioning | -2.2339 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Emotional Functioning | 2.2547 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Cognitive Functioning | -3.8401 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Social Functioning | -4.6198 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Global health Status /QoL (ql) | 0.3855 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Fatique | 2.1779 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Nausea/Vomitting | 4.7597 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Pain | 1.5926 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Dyspnoea | 0.5046 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Insomnia | -7.5026 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Appetite loss | 10.9601 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Constipation | 4.0855 units on a scale |
| Temozolomide | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ - C30) at Baseline, Post-Baseline (up to Month 30) | Diarrhoea | -0.1455 units on a scale |
Comparison: Physical Functioning. Analysis of variance (ANOVA) included all post-baseline data (Months 3 through 21).p-value: 0.497595% CI: [-3.9855, 8.186]ANOVA
Comparison: Role Functioning. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.7695% CI: [-10.9358, 7.9951]ANOVA
Comparison: Emotional Functioning. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.994995% CI: [-7.035, 6.9895]ANOVA
Comparison: Cognitive Functioning. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.625395% CI: [-9.155, 5.5125]ANOVA
Comparison: Social Functioning. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.721995% CI: [-7.2953, 10.5205]ANOVA
Comparison: Global Health Status /QoL. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.244395% CI: [-2.4046, 9.4023]ANOVA
Comparison: Fatigue. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.328795% CI: [-10.0739, 3.3841]ANOVA
Comparison: Nausea/Vomiting. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.048595% CI: [-8.3635, -0.0285]ANOVA
Comparison: Pain. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.035495% CI: [-17.5629, -0.6271]ANOVA
Comparison: Dyspnoea. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.372495% CI: [-10.2784, 3.8608]ANOVA
Comparison: Insomnia. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.288495% CI: [-13.9002, 4.1482]ANOVA
Comparison: Appetite loss. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.408195% CI: [-9.3926, 3.8282]ANOVA
Comparison: Constipation. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.27595% CI: [-11.0245, 3.1495]ANOVA
Comparison: Diarrhoea. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.021395% CI: [-11.4129, -0.9241]ANOVA
Comparison: Financial Problems. ANOVA included all post-baseline data (Months 3 through 21).p-value: 0.520195% CI: [-11.0727, 5.6137]ANOVA
Secondary
Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR)
BOR was defined as the best response observed for a participant during assessment. Number of participants who had BOR as CR and number of participants who had BOR as CR or PR were reported. Complete response was defined as disappearance of all enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, off steroids, and neurologically stable or improved. Partial response was defined as 50% reduction in size of enhancing tumor on consecutive Gd-MRI scans at least 1 month apart, steroids stable or reduced, and neurologically stable or improved.
Time frame: 4 week after radiotherapy (RT) (up to Week 4), >4 Week after RT (up to Week 8) and Month 6
Population: ITT population. Data were analyzed according to the treatment randomized (as randomized). Here, number of participants analyzed = participants who were evaluable for this outcome and n = participants who were evaluable of specified time-point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Irinotecan | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR at 4 weeks after RT (n=110,46) | 11 participants |
| Bevacizumab + Irinotecan | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR at >4 weeks after RT (n=95,35) | 11 participants |
| Bevacizumab + Irinotecan | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR at Month 6 (n=91,28) | 3 participants |
| Bevacizumab + Irinotecan | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR or PR at 4 Week after RT (n=110,46) | 42 participants |
| Bevacizumab + Irinotecan | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR or PR at >4 Week after RT (n=95,35) | 18 participants |
| Bevacizumab + Irinotecan | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR or PR at Month 6 (n=91,28) | 5 participants |
| Temozolomide | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR or PR at >4 Week after RT (n=95,35) | 3 participants |
| Temozolomide | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR at 4 weeks after RT (n=110,46) | 2 participants |
| Temozolomide | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR or PR at 4 Week after RT (n=110,46) | 6 participants |
| Temozolomide | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR at >4 weeks after RT (n=95,35) | 1 participants |
| Temozolomide | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR or PR at Month 6 (n=91,28) | 3 participants |
| Temozolomide | Number of Participants With A Best Overall Response (BOR) of Complete Response (CR) and With A BOR of CR or Partial Response (PR) | CR at Month 6 (n=91,28) | 1 participants |
Comparison: Response rate based on participants with CR at 4 weeks after RT.p-value: 0.3474595% CI: [-0.02, 0.14]Fisher Exact
Comparison: The response rate based on participants with CR at \>4 weeks after RT.p-value: 0.1792395% CI: [0, 0.17]Fisher Exact
Comparison: The response rate based on participants with CR at Month 6.p-value: 195% CI: [-0.08, 0.08]Fisher Exact
Comparison: Response rate based on participants with CR or PR at 4 weeks after RT.p-value: 0.002195% CI: [0.12, 0.38]Fisher Exact
Comparison: Response rate based on participants with CR and PR at \>4 weeks after RT.p-value: 0.1876195% CI: [-0.02, 0.23]Fisher Exact
Comparison: Response rate based on participants with CR or PR at Month 6.p-value: 0.3897495% CI: [-0.18, 0.07]Fisher Exact
Secondary
Overall Survival (OS)
Overall survival was defined as the time from randomization to death from any cause. OS was estimated using Kaplan-Meier method.
Time frame: From baseline until death (up to 4.5 years)
Population: ITT population. Data were analyzed according to the treatment randomized (as randomized).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Irinotecan | Overall Survival (OS) | 16.64 Months |
| Temozolomide | Overall Survival (OS) | 17.30 Months |
p-value: 0.828395% CI: [0.684, 1.354]Chi-squared
Secondary
Percentage of Participants Who Discontinued
Discontinuation was defined as the percentage of participants who permanently discontinued treatment in either treatment arm. Percentage of participant with individual discontinuation reason are reported. CNS: central nervous system; CTCAE: Common Terminology Criteria for Adverse Events . Other reason refers to any other reason than the specified ones.
Time frame: From baseline until death (up to 4.5 years)
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Proteinuria (nephrotic syndrome) (CTCAE Grade 4) | 0.9 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Other | 9.5 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Regular | 1.7 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Persisting non-hematological toxicity CTCAE Grade3 | 0 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Repeated CTCAE Grade 4 hematological toxicity | 0 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Participant's wish | 6 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Venous thrombosis/embolism | 0.9 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Gastro-intestinal perforation (CTCAE Grade 1-4) | 0.9 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Wound dehiscence requiring medical intervention | 0.9 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Progressive disease | 74.1 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | Wound dehiscence requiring surgical intervention | 4.3 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants Who Discontinued | CNS hemorrhagic event (CTCAE Grade >1) | 0.9 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Wound dehiscence requiring surgical intervention | 0 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | CNS hemorrhagic event (CTCAE Grade >1) | 0 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Gastro-intestinal perforation (CTCAE Grade 1-4) | 0 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Other | 5.6 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Participant's wish | 5.6 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Progressive disease | 57.4 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Proteinuria (nephrotic syndrome) (CTCAE Grade 4) | 0 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Regular | 27.8 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Repeated CTCAE Grade 4 hematological toxicity | 0.9 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Venous thrombosis/embolism | 0 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Wound dehiscence requiring medical intervention | 0 percentage of participants |
| Temozolomide | Percentage of Participants Who Discontinued | Persisting non-hematological toxicity CTCAE Grade3 | 1.9 percentage of participants |
Secondary
Percentage of Participants Who Received Corticosteroid for Glioblastoma
Participants used corticosteroids for the glioblastoma condition. Corticosteroids included dexamethasone, methylprednisone, fortecortin, hydrocortisone, urbason, and prednisolone.
Time frame: From baseline to Month 6
Population: The safety population (SAF) was defined to include all participants who received at least 1 dose of study medication. Data were analyzed according to the treatment actually received (as treated).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + Irinotecan | Percentage of Participants Who Received Corticosteroid for Glioblastoma | 80.0 percentage of participants |
| Temozolomide | Percentage of Participants Who Received Corticosteroid for Glioblastoma | 78.7 percentage of participants |
Secondary
Percentage of Participants With Response on FLAIR Imaging
FLAIR lesions were determined as stable, progressive or decreased. FLAIR lesions was determined as progressive only if they were not be attributed to causes apart from tumor infiltration (sequelae of radiation therapy, demyelination, ischemia, infection, seizures, or other treatment effects). Percentage of participants are based on ITT population. Dis.=Discontinuation.
Time frame: At screening, Baseline, Month 6 and Therapy Discontinuation (Up to 4.5 years)
Population: ITT population. Here, n = participants with at least 1 assessment during specified time-point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Therapy Dis.:Progressiv FLAIR Lesions (n=55,31) | 29.3 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Screening: Initial Flair Lesion (n=116,54) | 72.4 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Screening:Stable Flair Lesion (n=116,54) | 17.2 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Baseline:Decreased FLAIR Lesions (n=105,46) | 16.4 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Baseline:Initial FLAIR Lesions (n=105,46) | 18.1 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Baseline:Progressive FLAIR Lesions (n=105,46) | 14.7 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Baseline: Stable FLAIR Lesions (n=105,46) | 41.4 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Month 6:Progressive FLAIR Lesions (n=91,28) | 16.4 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Month 6: Stable FLAIR Lesions (n=91,28) | 62.1 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Therapy Dis.:Decreased FLAIR Lesions (n=55,31) | 0.9 percentage of participants |
| Bevacizumab + Irinotecan | Percentage of Participants With Response on FLAIR Imaging | Therapy Dis.:Stable FLAIR Lesions (n=55,31) | 17.2 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Therapy Dis.:Stable FLAIR Lesions (n=55,31) | 29.6 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Baseline: Stable FLAIR Lesions (n=105,46) | 35.2 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Screening: Initial Flair Lesion (n=116,54) | 72.2 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Therapy Dis.:Decreased FLAIR Lesions (n=55,31) | 0.0 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Screening:Stable Flair Lesion (n=116,54) | 16.7 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Month 6:Progressive FLAIR Lesions (n=91,28) | 22.2 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Baseline:Decreased FLAIR Lesions (n=105,46) | 20.4 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Therapy Dis.:Progressiv FLAIR Lesions (n=55,31) | 27.8 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Baseline:Initial FLAIR Lesions (n=105,46) | 18.5 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Month 6: Stable FLAIR Lesions (n=91,28) | 29.6 percentage of participants |
| Temozolomide | Percentage of Participants With Response on FLAIR Imaging | Baseline:Progressive FLAIR Lesions (n=105,46) | 11.1 percentage of participants |
Secondary
Progression-Free Survival (PFS)
Progression-free survival was defined as the time from randomization to objective tumor progression or death from any cause, whichever came first. Progression was defined as 25% increase in size of enhancing tumor or any new tumor on Gd-MRI scans, or neurologically worse, and steroids stable or increased. PFS was estimated using Kaplan-Meier method.
Time frame: From baseline to the end of the study (up to 4.5 years)
Population: ITT population. Data were analyzed according to the treatment randomized (as randomized).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Irinotecan | Progression-Free Survival (PFS) | 9.74 Months |
| Temozolomide | Progression-Free Survival (PFS) | 5.99 Months |
p-value: 0.001295% CI: [0.423, 0.817]Chi-squared
Secondary
Time to Treatment Failure
Time frame: From baseline until end of study (up to 4.5 years)
Population: Data for this outcome measure were not collected as this outcome was removed as per changes in planned analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Irinotecan | Time to Treatment Failure | NA years |
| Temozolomide | Time to Treatment Failure | NA years |