Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) And Fotemustine in Patients With Recurrent Glioblastoma (NCT NCT01474239)

Last Updated: 2016-03-15

Results Overview

Overall survival (OS) was defined as the time in months from the start of treatment to death due to any cause. If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of magnetic resonance imaging (MRI) assessment, date of last treatment, date of discontinuation and date of last available follow-up visit. Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

91 participants

Primary outcome timeframe

6 months

Results posted on

2016-03-15

Participant Flow

Study included 28-day screening period. Participants were randomized according to a 2:1 ratio to one of the 2 treatment groups. A total of 99 participants were screened, of which 91 were randomized.

Participant milestones

Participant milestones
Measure	Bevacizumab Participants received bevacizumab 10 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine Participants received fotemustine 75 milligrams per square meter (mg/m\^2) via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Overall Study STARTED	59	32
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	59	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab Participants received bevacizumab 10 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine Participants received fotemustine 75 milligrams per square meter (mg/m\^2) via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Overall Study Disease Progression	37	25
Overall Study Adverse Event	12	3
Overall Study Withdrawal by Subject	1	2
Overall Study Death	1	1
Overall Study Clinical Disease Progression	7	1
Overall Study Withdrawal for Economic Reason	1	0

Baseline Characteristics

A Study of Avastin (Bevacizumab) And Fotemustine in Patients With Recurrent Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab n=59 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Total n=91 Participants Total of all reporting groups
Age, Continuous	56.86 years STANDARD_DEVIATION 9.40 • n=5 Participants	55.63 years STANDARD_DEVIATION 10.64 • n=7 Participants	56.43 years STANDARD_DEVIATION 9.81 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	9 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	23 Participants n=7 Participants	62 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Intent-to-Treat (ITT) population included all randomized participants with at least one administration of the study drug.

Outcome measures

Outcome measures
Measure	Bevacizumab n=59 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Percentage of Participants Alive 6 Months After Start of Treatment	62.07 percentage of participants Interval 48.37 to 74.49	73.33 percentage of participants Interval 54.11 to 87.72

PRIMARY outcome

Timeframe: Baseline until death (up to 691 days)

Population: ITT population.

OS was defined as the time in months from the start of treatment to death due to any cause. If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of MRI assessment, date of last treatment, date of discontinuation and date of last available follow-up visit. Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Bevacizumab n=59 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Overall Survival (OS)	7.26 months Interval 5.82 to 9.2	8.66 months Interval 6.34 to 15.38

SECONDARY outcome

Timeframe: 6 months

Population: ITT population.

Progression-free survival (PFS) was defined as the time in months from the start of treatment to the date of the first occurrence of disease progression or death from any cause, whichever occurred first. PFS was estimated by the Kaplan-Meier method. Progression was assessed using Response Assessment in Neuro-Oncology (RANO) or Macdonald Response Criteria, whichever occurred first. As per the RANO criteria, progression was defined as 25% or more increase in enhancing lesions despite stable or increasing steroid dose; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease). As per the Macdonald criteria, progression was defined as 25% or more increase in enhancing lesions; any new lesions; and clinical deterioration.

Outcome measures

Outcome measures
Measure	Bevacizumab n=59 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Percentage of Participants Who Were Alive and Progression Free 6 Months After Start of Treatment	26.32 percentage of participants Interval 15.54 to 39.66	10.71 percentage of participants Interval 2.27 to 28.23

SECONDARY outcome

Timeframe: Baseline until disease progression or death (baseline, 46 days after first administration of study drug, and thereafter every 56 days up to 691 days)

Population: ITT population.

PFS was defined as the time in months from the start of treatment to the date of the first occurrence of disease progression or death from any cause, whichever occurred first. PFS was estimated by the Kaplan-Meier method. Progression was assessed using the RANO or the Macdonald Response Criteria, whichever occurred first. As per RANO criteria, progression was defined as 25% or more increase in enhancing lesions despite stable or increasing steroid dose; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease). As per Macdonald criteria, progression was defined as 25% or more increase in enhancing lesions; any new lesions; and clinical deterioration.

Outcome measures

Outcome measures
Measure	Bevacizumab n=59 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Progression-Free Survival (PFS)	3.38 months Interval 3.15 to 4.37	3.45 months Interval 1.87 to 3.84

SECONDARY outcome

Timeframe: 9 months

Population: ITT population.

Outcome measures

Outcome measures
Measure	Bevacizumab n=59 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Percentage of Participants Alive 9 Months After Start of Treatment	37.93 percentage of participants Interval 25.51 to 51.63	46.67 percentage of participants Interval 28.34 to 65.67

SECONDARY outcome

Timeframe: 12 months

Population: ITT population. Here, the number of participants analyzed signified participants with evaluable data for this outcome.

Outcome measures

Outcome measures
Measure	Bevacizumab n=58 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=30 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Percentage of Participants Alive 12 Months After Start of Treatment	25.86 percentage of participants Interval 15.26 to 39.04	40.00 percentage of participants Interval 22.66 to 59.4

SECONDARY outcome

Timeframe: 30 days after last dose of study drug (up to Day 600)

Population: ITT population. Here, the number of participants analyzed signified participants with evaluable data for this outcome.

Outcome measures

Outcome measures
Measure	Bevacizumab n=58 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=30 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Percentage of Participants Alive 30 Days After Last Dose of Study Drug	93.10 percentage of participants Interval 83.27 to 98.09	90.00 percentage of participants Interval 73.47 to 97.89

SECONDARY outcome

Timeframe: Baseline until disease progression or death (baseline, 46 days after first administration of study drug, and thereafter every 56 days up to 691 days)

Population: ITT population.

Percentage of participants achieving CR or PR as overall response between first drug administration and documented disease progression were calculated. Tumor response was evaluated according to both the RANO and the Macdonald response criteria. As per Macdonald criteria, CR was defined as the disappearance of all enhancing disease, sustained for at least 4 weeks, and no new lesions along with clinical features of clinically stable or improved, with no corticosteroid; PR was defined as a 50% or more decrease of all measurable enhancing lesions, sustained for at least 4 weeks, and no new lesion along with clinical features of clinically stable or improved, with stable or reduced corticosteroids. RANO criteria defined CR and PR the same as Macdonald criteria with the following additions: CR - improved non enhancing T2/FLAIR lesions; PR - no progression of non-measurable disease, stable or improved non enhancing FLAIR/T2 lesions.

Outcome measures

Outcome measures
Measure	Bevacizumab n=59 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) RANO Evaluation	28.81 percentage of participants	9.38 percentage of participants
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) MacDonald Evaluation	28.81 percentage of participants	6.25 percentage of participants

SECONDARY outcome

Timeframe: Screening, Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72

Population: ITT population. Here, the number of participants analyzed signified participants with evaluable data for this outcome, and "n" signified participants with evaluable data for specified category for each arm, respectively.

EORTC QLQ-C30: included global health status/quality of life (QOL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; a higher score for Global QOL/functional scales indicates better level of QOL/functioning, or a higher score for symptom scale indicates greater degree of symptoms.

Outcome measures

Outcome measures
Measure	Bevacizumab n=58 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=31 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Role Fn: Change at Week 64 (n=1,0)	-50.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Emotional Fn: Change at Week 48 (n=4,1)	14.58 units on a scale Standard Deviation 27.53	8.33 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Emotional Fn: Change at Week 56 (n=4,0)	-4.17 units on a scale Standard Deviation 27.64	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Nausea: Change at Week 8 (n=27,16)	1.85 units on a scale Standard Deviation 10.68	-8.33 units on a scale Standard Deviation 14.91
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Diarrhea: Screening (n=58,31)	1.15 units on a scale Standard Deviation 6.14	2.15 units on a scale Standard Deviation 8.32
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Social Fn: Change at Week 32 (n=7,2)	-7.14 units on a scale Standard Deviation 38.32	8.33 units on a scale Standard Deviation 11.79
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Physical Functioning (Fn): Screening (n=58,31)	71.95 units on a scale Standard Deviation 25.65	78.92 units on a scale Standard Deviation 25.07
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Physical Fn: Change at Week 8 (n=27,16)	10.37 units on a scale Standard Deviation 19.07	7.08 units on a scale Standard Deviation 12.76
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Physical Fn: Change at Week 16 (n=15,7)	7.56 units on a scale Standard Deviation 19.17	8.57 units on a scale Standard Deviation 13.72
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Physical Fn: Change at Week 24 (n=14,1)	13.81 units on a scale Standard Deviation 24.17	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Physical Fn: Change at Week 32 (n=7,2)	18.10 units on a scale Standard Deviation 28.21	13.33 units on a scale Standard Deviation 9.43
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Physical Fn: Change at Week 40 (n=9,1)	4.44 units on a scale Standard Deviation 19.72	6.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Physical Fn: Change at Week 48 (n=4,1)	3.33 units on a scale Standard Deviation 16.78	6.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Physical Fn: Change at Week 56 (n=4,0)	6.67 units on a scale Standard Deviation 9.43	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Physical Fn: Change at Week 64 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Physical Fn: Change at Week 72 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Role Fn: Screening (n=58,31)	67.82 units on a scale Standard Deviation 31.04	73.66 units on a scale Standard Deviation 32.14
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Role Fn: Change at Week 8 (n=27,16)	6.17 units on a scale Standard Deviation 34.01	4.17 units on a scale Standard Deviation 21.52
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Role Fn: Change at Week 16 (n=15,7)	2.22 units on a scale Standard Deviation 25.87	2.38 units on a scale Standard Deviation 26.23
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Role Fn: Change at Week 24 (n=14,1)	14.29 units on a scale Standard Deviation 33.88	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Role Fn: Change at Week 32 (n=7,2)	16.67 units on a scale Standard Deviation 28.87	0.00 units on a scale Standard Deviation 0.00
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Role Fn: Change at Week 40 (n=9,1)	0.00 units on a scale Standard Deviation 22.05	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Role Fn: Change at Week 48 (n=4,1)	0.00 units on a scale Standard Deviation 36.00	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Role Fn: Change at Week 56 (n=4,0)	-12.50 units on a scale Standard Deviation 36.96	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Role Fn: Change at Week 72 (n=1,0)	-50.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Emotional Fn: Screening (n=58,31)	73.56 units on a scale Standard Deviation 23.47	74.19 units on a scale Standard Deviation 23.41
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Emotional Fn: Change at Week 8 (n=27,16)	-8.02 units on a scale Standard Deviation 23.62	8.33 units on a scale Standard Deviation 24.91
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Emotional Fn: Change at Week 16 (n=15,7)	-0.56 units on a scale Standard Deviation 14.25	-2.38 units on a scale Standard Deviation 27.52
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Emotional Fn: Change at Week 24 (n=14,1)	10.12 units on a scale Standard Deviation 29.63	-33.33 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Emotional Fn: Change at Week 32 (n=7,2)	-2.38 units on a scale Standard Deviation 15.00	16.67 units on a scale Standard Deviation 0.00
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Emotional Fn: Change at Week 40 (n=9,1)	-5.56 units on a scale Standard Deviation 24.65	8.33 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Emotional Fn: Change at Week 64 (n=1,0)	8.33 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Emotional Fn: Change at Week 72 (n=1,0)	8.33 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Cognitive Fn: Screening (n=58,31)	70.40 units on a scale Standard Deviation 25.18	79.03 units on a scale Standard Deviation 24.33
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Cognitive Fn: Change at Week 8 (n=27,16)	4.94 units on a scale Standard Deviation 23.49	7.29 units on a scale Standard Deviation 23.55
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Cognitive Fn: Change at Week 16 (n=15,7)	2.22 units on a scale Standard Deviation 17.67	-4.76 units on a scale Standard Deviation 34.31
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Cognitive Fn: Change at Week 24 (n=14,1)	10.71 units on a scale Standard Deviation 24.11	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Cognitive Fn: Change at Week 32 (n=7,2)	0.00 units on a scale Standard Deviation 16.67	8.33 units on a scale Standard Deviation 11.79
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Cognitive Fn: Change at Week 40 (n=9,1)	-1.85 units on a scale Standard Deviation 19.44	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Cognitive Fn: Change at Week 48 (n=4,1)	0.00 units on a scale Standard Deviation 0.00	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Cognitive Fn: Change at Week 56 (n=4,0)	-4.17 units on a scale Standard Deviation 20.97	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Cognitive Fn: Change at Week 64 (n=1,0)	16.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Cognitive Fn: Change at Week 72 (n=1,0)	16.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Social Fn: Screening (n=58,31)	72.99 units on a scale Standard Deviation 28.07	81.18 units on a scale Standard Deviation 24.24
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Social Fn: Change at Week 8 (n=27,16)	1.85 units on a scale Standard Deviation 31.12	4.17 units on a scale Standard Deviation 23.96
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Social Fn: Change at Week 16 (n=15,7)	1.11 units on a scale Standard Deviation 27.07	-2.38 units on a scale Standard Deviation 26.23
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Social Fn: Change at Week 24 (n=14,1)	13.10 units on a scale Standard Deviation 39.32	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Social Fn: Change at Week 40 (n=9,1)	-5.56 units on a scale Standard Deviation 22.05	16.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Social Fn: Change at Week 48 (n=4,1)	-4.17 units on a scale Standard Deviation 36.96	16.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Social Fn: Change at Week 56 (n=4,0)	-12.50 units on a scale Standard Deviation 28.46	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Social Fn: Change at Week 64 (n=1,0)	-66.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Social Fn: Change at Week 72 (n=1,0)	-66.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 QOL: Screening (n=58,31)	58.05 units on a scale Standard Deviation 26.40	66.13 units on a scale Standard Deviation 24.90
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 QOL: Change at Week 8 (n=27,16)	-3.09 units on a scale Standard Deviation 20.17	6.25 units on a scale Standard Deviation 22.87
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 QOL: Change at Week 16 (n=15,7)	-4.44 units on a scale Standard Deviation 14.39	7.14 units on a scale Standard Deviation 23.78
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 QOL: Change at Week 24 (n=14,1)	4.76 units on a scale Standard Deviation 21.11	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 QOL: Change at Week 32 (n=7,2)	3.57 units on a scale Standard Deviation 17.91	-12.50 units on a scale Standard Deviation 17.68
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 QOL: Change at Week 40 (n=9,1)	-2.78 units on a scale Standard Deviation 25.34	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 QOL: Change at Week 48 (n=4,1)	10.42 units on a scale Standard Deviation 14.23	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 QOL: Change at Week 56 (n=4,0)	2.08 units on a scale Standard Deviation 34.94	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 QOL: Change at Week 64 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 QOL: Change at Week 72 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Fatigue: Screening (n=58,31)	31.99 units on a scale Standard Deviation 25.50	24.01 units on a scale Standard Deviation 22.05
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Fatigue: Change at Week 8 (n=27,16)	-3.29 units on a scale Standard Deviation 32.59	-13.19 units on a scale Standard Deviation 25.73
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Fatigue: Change at Week 16 (n=15,7)	2.22 units on a scale Standard Deviation 21.50	-9.52 units on a scale Standard Deviation 17.48
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Fatigue: Change at Week 24 (n=14,1)	-6.35 units on a scale Standard Deviation 29.79	-11.11 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Fatigue: Change at Week 32 (n=7,2)	3.17 units on a scale Standard Deviation 17.82	-5.56 units on a scale Standard Deviation 7.86
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Fatigue: Change at Week 40 (n=9,1)	9.88 units on a scale Standard Deviation 23.20	-11.11 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Fatigue: Change at Week 48 (n=4,1)	-8.33 units on a scale Standard Deviation 18.98	-11.11 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Fatigue: Change at Week 56 (n=4,0)	2.78 units on a scale Standard Deviation 30.60	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Fatigue: Change at Week 64 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Fatigue: Change at Week 72 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Nausea: Screening (n=58,31)	2.01 units on a scale Standard Deviation 7.70	1.08 units on a scale Standard Deviation 4.16
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Nausea: Change at Week 16 (n=15,7)	0.00 units on a scale Standard Deviation 6.30	-14.29 units on a scale Standard Deviation 20.25
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Nausea: Change at Week 24 (n=14,1)	-5.95 units on a scale Standard Deviation 10.56	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Nausea: Change at Week 32 (n=7,2)	-2.38 units on a scale Standard Deviation 6.30	0.00 units on a scale Standard Deviation 0.00
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Constipation: Change at Week 16 (n=15,7)	4.44 units on a scale Standard Deviation 17.21	-9.52 units on a scale Standard Deviation 25.20
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Nausea: Change at Week 40 (n=9,1)	-9.26 units on a scale Standard Deviation 8.78	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Nausea: Change at Week 48 (n=4,1)	0.00 units on a scale Standard Deviation 0.00	-16.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Nausea: Change at Week 56 (n=4,0)	-4.17 units on a scale Standard Deviation 8.33	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Nausea: Change at Week 64 (n=1,0)	-16.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Nausea: Change at Week 72 (n=1,0)	-16.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Pain: Screening (n=58,31)	6.90 units on a scale Standard Deviation 16.82	14.52 units on a scale Standard Deviation 23.47
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Pain: Change at Week 8 (n=27,16)	-1.85 units on a scale Standard Deviation 24.61	-6.25 units on a scale Standard Deviation 26.44
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Pain: Change at Week 16 (n=15,7)	-10.00 units on a scale Standard Deviation 19.72	-2.38 units on a scale Standard Deviation 20.25
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Pain: Change at Week 24 (n=14,1)	-8.33 units on a scale Standard Deviation 28.31	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Pain: Change at Week 32 (n=7,2)	0.00 units on a scale Standard Deviation 16.67	-8.33 units on a scale Standard Deviation 11.79
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Pain: Change at Week 40 (n=9,1)	-7.41 units on a scale Standard Deviation 18.84	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Pain: Change at Week 48 (n=4,1)	-29.17 units on a scale Standard Deviation 28.46	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Pain: Change at Week 56 (n=4,0)	0.00 units on a scale Standard Deviation 19.25	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Pain: Change at Week 64 (n=1,0)	-16.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Pain: Change at Week 72 (n=1,0)	-16.67 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Dyspnea: Screening (n=58,31)	11.49 units on a scale Standard Deviation 22.12	3.23 units on a scale Standard Deviation 10.02
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Dyspnea: Change at Week 8 (n=27,16)	4.94 units on a scale Standard Deviation 28.80	-6.25 units on a scale Standard Deviation 21.84
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Dyspnea: Change at Week 16 (n=15,7)	0.00 units on a scale Standard Deviation 25.20	4.76 units on a scale Standard Deviation 12.60
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Dyspnea: Change at Week 24 (n=14,1)	-9.52 units on a scale Standard Deviation 27.51	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Dyspnea: Change at Week 32 (n=7,2)	0.00 units on a scale Standard Deviation 27.22	0.00 units on a scale Standard Deviation 0.00
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Dyspnea: Change at Week 40 (n=9,1)	3.70 units on a scale Standard Deviation 20.03	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Dyspnea: Change at Week 48 (n=4,1)	-8.33 units on a scale Standard Deviation 16.67	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Dyspnea: Change at Week 56 (n=4,0)	0.00 units on a scale Standard Deviation 27.22	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Dyspnea: Change at Week 64 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Dyspnea: Change at Week 72 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Insomnia: Screening (n=58,31)	18.39 units on a scale Standard Deviation 28.73	18.28 units on a scale Standard Deviation 22.51
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Insomnia: Change at Week 8 (n=27,16)	1.23 units on a scale Standard Deviation 25.29	-8.33 units on a scale Standard Deviation 33.33
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Insomnia: Change at Week 16 (n=15,7)	2.22 units on a scale Standard Deviation 32.04	-4.76 units on a scale Standard Deviation 29.99
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Insomnia: Change at Week 24 (n=14,1)	-9.52 units on a scale Standard Deviation 46.09	-33.33 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Insomnia: Change at Week 32 (n=7,2)	28.57 units on a scale Standard Deviation 23.00	16.67 units on a scale Standard Deviation 23.57
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Insomnia: Change at Week 40 (n=9,1)	14.81 units on a scale Standard Deviation 24.22	33.33 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Insomnia: Change at Week 48 (n=4,1)	25.00 units on a scale Standard Deviation 31.91	33.33 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Insomnia: Change at Week 56 (n=4,0)	33.33 units on a scale Standard Deviation 27.22	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Insomnia: Change at Week 64 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Insomnia: Change at Week 72 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Appetite loss: Screening (n=58,31)	7.47 units on a scale Standard Deviation 19.79	5.38 units on a scale Standard Deviation 12.46
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Appetite loss: Change at Week 8 (n=27,16)	0.00 units on a scale Standard Deviation 22.65	-10.42 units on a scale Standard Deviation 23.47
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Appetite loss: Change at Week 16 (n=15,7)	-2.22 units on a scale Standard Deviation 8.61	-14.29 units on a scale Standard Deviation 26.23
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Appetite loss: Change at Week 24 (n=14,1)	-7.14 units on a scale Standard Deviation 19.30	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Appetite loss: Change at Week 32 (n=7,2)	-4.76 units on a scale Standard Deviation 12.60	0.00 units on a scale Standard Deviation 0.00
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Appetite loss: Change at Week 40 (n=9,1)	-7.41 units on a scale Standard Deviation 14.70	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Appetite loss: Change at Week 48 (n=4,1)	-16.67 units on a scale Standard Deviation 19.25	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Appetite loss: Change at Week 56 (n=4,0)	-16.67 units on a scale Standard Deviation 19.25	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Appetite loss: Change at Week 64 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Appetite loss: Change at Week 72 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Constipation: Screening (n=58,31)	17.82 units on a scale Standard Deviation 24.36	17.20 units on a scale Standard Deviation 25.63
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Constipation: Change at Week 8 (n=26,16)	3.85 units on a scale Standard Deviation 25.52	-4.17 units on a scale Standard Deviation 26.87
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Constipation: Change at Week 24 (n=14,1)	2.38 units on a scale Standard Deviation 20.52	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Constipation: Change at Week 32 (n=7,2)	-0.00 units on a scale Standard Deviation 38.49	16.67 units on a scale Standard Deviation 23.57
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Constipation: Change at Week 40 (n=9,1)	3.70 units on a scale Standard Deviation 26.06	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Constipation: Change at Week 48 (n=4,1)	-16.67 units on a scale Standard Deviation 19.25	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Constipation: Change at Week 56 (n=4,0)	0.00 units on a scale Standard Deviation 27.22	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Constipation: Change at Week 64 (n=1,0)	-33.33 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Constipation: Change at Week 72 (n=1,0)	-33.33 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Diarrhea: Change at Week 8 (n=27,16)	0.00 units on a scale Standard Deviation 9.25	0.00 units on a scale Standard Deviation 0.00
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Diarrhea: Change at Week 16 (n=15,7)	-6.67 units on a scale Standard Deviation 18.69	0.00 units on a scale Standard Deviation 0.00
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Diarrhea: Change at Week 24 (n=14,1)	-7.14 units on a scale Standard Deviation 19.30	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Diarrhea: Change at Week 32 (n=7,2)	-4.76 units on a scale Standard Deviation 12.60	0.00 units on a scale Standard Deviation 0.00
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Diarrhea: Change at Week 40 (n=9,1)	0.00 units on a scale Standard Deviation 0.00	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Diarrhea: Change at Week 48 (n=4,1)	0.00 units on a scale Standard Deviation 0.00	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Diarrhea: Change at Week 56 (n=4,0)	0.00 units on a scale Standard Deviation 0.00	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Diarrhea: Change at Week 64 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Diarrhea: Change at Week 72 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Financial Fn: Screening (n=58,31)	17.82 units on a scale Standard Deviation 25.91	25.81 units on a scale Standard Deviation 34.11
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Financial Fn: Change at Week 8 (n=27,16)	6.17 units on a scale Standard Deviation 26.21	-4.17 units on a scale Standard Deviation 11.39
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Financial Fn: Change at Week 16 (n=15,7)	2.22 units on a scale Standard Deviation 15.26	9.52 units on a scale Standard Deviation 46.00
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Financial Fn: Change at Week 24 (n=14,1)	-4.76 units on a scale Standard Deviation 22.10	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Financial Fn: Change at Week 32 (n=7,2)	0.00 units on a scale Standard Deviation 19.25	-16.67 units on a scale Standard Deviation 23.57
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Financial Fn: Change at Week 40 (n=9,1)	-3.70 units on a scale Standard Deviation 26.06	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Financial Fn: Change at Week 48 (n=4,1)	-16.67 units on a scale Standard Deviation 19.25	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Financial Fn: Change at Week 56 (n=4,0)	-8.33 units on a scale Standard Deviation 31.91	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Financial Fn: Change at Week 64 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.
Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 Financial Fn: Change at Week 72 (n=1,0)	0.00 units on a scale Standard Deviation NA Standard deviation not available as only 1 participant was evaluable.	NA units on a scale Standard Deviation NA Data not available as no participant was evaluable.

SECONDARY outcome

Timeframe: Baseline until recurrence (up to 691 days)

Population: ITT population. Number of participants analyzed signified participants who were not receiving corticosteroids at screening.

Corticosteroid initiation was assessed in participants not receiving corticosteroids at screening. The participant had the event if he/she started on corticosteroids with a dosage greater than equal to (\>/=) 2 mg dexamethasone equivalent.

Outcome measures

Outcome measures
Measure	Bevacizumab n=17 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=12 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Percentage of Participants With Corticosteroid Initiation During the Study Period	58.82 percentage of participants	41.67 percentage of participants

SECONDARY outcome

Timeframe: Baseline until recurrence (up to 691 days)

Population: ITT population. Number of participants analyzed signified participants who were not receiving corticosteroids at screening.

Time to corticosteroid initiation was defined as the time from screening to the start date of the first corticosteroid administration in participants not receiving corticosteroids at screening. The participant had the event if he/she started on corticosteroids with a dosage ≥2 mg dexamethasone equivalent. Instead, if the participant was not known to have the event, time was censored at the last available visit date. Time to corticosteroid initiation was estimated using Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Bevacizumab n=17 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=12 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Time to Corticosteroid Initiation	4.49 months Interval 1.87 to The upper limit of 95% confidence interval (CI) was not reached due to higher number (\>40%) of censored participants.	5.93 months Interval 0.3 to The upper limit of 95% confidence interval (CI) was not reached due to higher number (\>40%) of censored participants.

SECONDARY outcome

Timeframe: Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, post-treatment follow-up (up to Day 691)

Corticosteroid use was classified as: 1. No Change (if corticosteroid dose at each assessment was equal to baseline); 2. Decreased (if corticosteroid dose at each assessment was lower than baseline); 3. Increased (corticosteroid dose at each assessment was greater than baseline).

Outcome measures

Outcome measures
Measure	Bevacizumab n=52 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=28 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Percentage of Participants in Each Class of Corticosteroid Use Week 16: Decreased (n=33,18)	36.36 percentage of participants	27.78 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Follow-up: Decreased (n=9,3)	0.00 percentage of participants	33.33 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 8: Increased (n=52,28)	17.31 percentage of participants	17.86 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 8: Decreased (n=52,28)	23.08 percentage of participants	21.43 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 8: No Change (n=52,28)	59.62 percentage of participants	60.71 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 16: Increased (n=33,18)	21.21 percentage of participants	22.22 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 16: No Change (n=33,18)	42.42 percentage of participants	50.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 24: Increased (n=21,5)	28.57 percentage of participants	20.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 24: Decreased (n=21,5)	33.33 percentage of participants	40.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 24: No Change (n=21,5)	38.10 percentage of participants	40.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 32: Increased (n=14,3)	14.29 percentage of participants	33.33 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 32: Decreased (n=14,3)	42.86 percentage of participants	0.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 32: No Change (n=14,3)	42.86 percentage of participants	66.67 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 40: Increased (n=10,2)	0.00 percentage of participants	50.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 40: Decreased (n=10,2)	60.00 percentage of participants	0.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 40: No Change (n=10,2)	40.00 percentage of participants	50.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 48: Increased (n=8,1)	0.00 percentage of participants	0.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 48: Decreased (n=8,1)	50.00 percentage of participants	0.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 48: No Change (n=8,1)	50.00 percentage of participants	100.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 56: Increased (n=6,1)	0.00 percentage of participants	0.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 56: Decreased (n=6,1)	33.33 percentage of participants	0.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 56: No Change (n=6,1)	66.67 percentage of participants	100.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 64: Increased (n=3,1)	0.00 percentage of participants	0.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 64: Decreased (n=3,1)	0.00 percentage of participants	0.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 64: No Change (n=3,1)	100.00 percentage of participants	100.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Week 72: Increased (n=3,0)	0.00 percentage of participants	NA percentage of participants Data not available as no participant was evaluable.
Percentage of Participants in Each Class of Corticosteroid Use Week 72: Decreased (n=3,0)	0.00 percentage of participants	NA percentage of participants Data not available as no participant was evaluable.
Percentage of Participants in Each Class of Corticosteroid Use Week 72: No Change (n=3,0)	100.00 percentage of participants	NA percentage of participants Data not available as no participant was evaluable.
Percentage of Participants in Each Class of Corticosteroid Use Week 80: Increased (n=1,0)	0.00 percentage of participants	NA percentage of participants Data not available as no participant was evaluable.
Percentage of Participants in Each Class of Corticosteroid Use Week 80: Decreased (n=1,0)	0.00 percentage of participants	NA percentage of participants Data not available as no participant was evaluable.
Percentage of Participants in Each Class of Corticosteroid Use Week 80: No Change (n=1,0)	100.00 percentage of participants	NA percentage of participants Data not available as no participant was evaluable.
Percentage of Participants in Each Class of Corticosteroid Use Week 88: Increased (n=1,0)	100.00 percentage of participants	NA percentage of participants Data not available as no participant was evaluable.
Percentage of Participants in Each Class of Corticosteroid Use Week 88: Decreased (n=1,0)	0.00 percentage of participants	NA percentage of participants Data not available as no participant was evaluable.
Percentage of Participants in Each Class of Corticosteroid Use Week 88: No Change (n=1,0)	0.00 percentage of participants	NA percentage of participants Data not available as no participant was evaluable.
Percentage of Participants in Each Class of Corticosteroid Use Follow-up: Increased (n=9,3)	33.33 percentage of participants	0.00 percentage of participants
Percentage of Participants in Each Class of Corticosteroid Use Follow-up: No Change (n=9,3)	66.67 percentage of participants	66.67 percentage of participants

SECONDARY outcome

Timeframe: Baseline until KPS deterioration (up to 691 days)

Population: ITT population. Here, number of participants analyzed signified participants with evaluable data for this outcome.

Deterioration of KPS was defined as a decrease of at least 20 percentage points with respect to the screening. KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks.

Outcome measures

Outcome measures
Measure	Bevacizumab n=37 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=14 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Percentage of Participants With Karnofsky Performance Status (KPS) Deterioration	18.92 percentage of participants	14.29 percentage of participants

SECONDARY outcome

Timeframe: Baseline until KPS deterioration (up to 691 days)

Population: ITT population. Here, number of participants analyzed signified participants with evaluable data for this outcome.

Time to KPS deterioration was defined as the time from screening to the first date of deterioration of the KPS score. Deterioration of KPS was defined as a decrease of at least 20 percentage points with respect to the screening. KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks. Time to KPS deterioration was estimated using Kaplan Meier method. If the participant was not known to have the event, time was censored at the last available visit date.

Outcome measures

Outcome measures
Measure	Bevacizumab n=37 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=14 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Time to Karnofsky Performance Status (KPS) Deterioration	NA months Median was not reached as \<50% of participants had an event of interest.	NA months Median was not reached as \<50% of participants had an event of interest.

SECONDARY outcome

Timeframe: Baseline until WHO PS deterioration (Up to 691 days)

Population: ITT population.

WHO PS deterioration was defined as a decrease of at least 1 point with respect to the screening value. WHO PS is a 6-level score which ranges between 0 (fully active) to 5 (death); a lower score represents a higher ability to perform daily tasks.

Outcome measures

Outcome measures
Measure	Bevacizumab n=59 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Percentage of Participants With World Health Organization (WHO) Performance Status (PS) Deterioration	47.46 percentage of participants	37.50 percentage of participants

SECONDARY outcome

Timeframe: Baseline until WHO PS deterioration (Up to 691 days)

Population: ITT population.

Time to WHO PS deterioration was defined as the time from randomization to the first date of deterioration of the WHO performance status score. WHO PS deterioration was defined as a decrease of at least 1 point with respect to the screening value. WHO PS is a 6-level score which ranges between 0 (fully active) to 5 (death); a lower score represents a higher ability to perform daily tasks.

Outcome measures

Outcome measures
Measure	Bevacizumab n=59 Participants Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 Participants Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Time to WHO PS Deterioration	8.87 months Interval 4.17 to Data could not be estimated as \<50% of participants had an event of interest.	NA months Data could not be estimated as \<50% of participants had an event of interest.

Adverse Events

Bevacizumab

Serious events: 17 serious events

Other events: 35 other events

Deaths: 0 deaths

Fotemustine

Serious events: 6 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bevacizumab n=59 participants at risk Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 participants at risk Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Blood and lymphatic system disorders Leukopenia	0.00% 0/59 • Up to 691 days	3.1% 1/32 • Up to 691 days
Blood and lymphatic system disorders Pancytopenia	0.00% 0/59 • Up to 691 days	3.1% 1/32 • Up to 691 days
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/59 • Up to 691 days	3.1% 1/32 • Up to 691 days
Cardiac disorders Acute myocardial infarction	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Gastrointestinal disorders Abdominal pain	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Gastrointestinal disorders Ascites	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Gastrointestinal disorders Intestinal perforation	3.4% 2/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
General disorders Condition aggravated	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
General disorders Pyrexia	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Infections and infestations Anal abscess	0.00% 0/59 • Up to 691 days	3.1% 1/32 • Up to 691 days
Infections and infestations Orchitis	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Infections and infestations Respiratory tract infection	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/59 • Up to 691 days	3.1% 1/32 • Up to 691 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Nervous system disorders Cerebral haemorrhage	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Nervous system disorders Cerebral ischaemia	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Nervous system disorders Convulsion	3.4% 2/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Nervous system disorders Epilepsy	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Nervous system disorders Partial seizures with secondary generalisation	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Nervous system disorders Status epilepticus	0.00% 0/59 • Up to 691 days	3.1% 1/32 • Up to 691 days
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.4% 2/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Vascular disorders Thrombophlebitis	1.7% 1/59 • Up to 691 days	0.00% 0/32 • Up to 691 days

Other adverse events

Other adverse events
Measure	Bevacizumab n=59 participants at risk Participants received bevacizumab 10 mg/kg via IV infusion every 14 days until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.	Fotemustine n=32 participants at risk Participants received fotemustine 75 mg/m\^2 via IV infusion on Days 1, 8, and 15 (induction phase), followed by a 35-day drug-free interval, and then fotemustine 100 mg/m\^2 every 21 days (maintenance phase) until disease progression was radiographically documented or the onset of toxicity prevented treatment continuation.
Blood and lymphatic system disorders Anaemia	1.7% 1/59 • Up to 691 days	15.6% 5/32 • Up to 691 days
Blood and lymphatic system disorders Leukopenia	1.7% 1/59 • Up to 691 days	9.4% 3/32 • Up to 691 days
Blood and lymphatic system disorders Neutropenia	3.4% 2/59 • Up to 691 days	25.0% 8/32 • Up to 691 days
Blood and lymphatic system disorders Thrombocytopenia	3.4% 2/59 • Up to 691 days	43.8% 14/32 • Up to 691 days
Gastrointestinal disorders Constipation	5.1% 3/59 • Up to 691 days	6.2% 2/32 • Up to 691 days
Gastrointestinal disorders Diarrhoea	5.1% 3/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Gastrointestinal disorders Nausea	3.4% 2/59 • Up to 691 days	12.5% 4/32 • Up to 691 days
General disorders Asthenia	22.0% 13/59 • Up to 691 days	12.5% 4/32 • Up to 691 days
General disorders Fatigue	1.7% 1/59 • Up to 691 days	6.2% 2/32 • Up to 691 days
General disorders Oedema peripheral	1.7% 1/59 • Up to 691 days	6.2% 2/32 • Up to 691 days
General disorders Pyrexia	8.5% 5/59 • Up to 691 days	9.4% 3/32 • Up to 691 days
Infections and infestations Fungal infection	1.7% 1/59 • Up to 691 days	9.4% 3/32 • Up to 691 days
Infections and infestations Urinary tract infection	5.1% 3/59 • Up to 691 days	3.1% 1/32 • Up to 691 days
Investigations Transaminases increased	5.1% 3/59 • Up to 691 days	12.5% 4/32 • Up to 691 days
Investigations Weight increased	6.8% 4/59 • Up to 691 days	3.1% 1/32 • Up to 691 days
Nervous system disorders Convulsion	6.8% 4/59 • Up to 691 days	6.2% 2/32 • Up to 691 days
Nervous system disorders Epilepsy	3.4% 2/59 • Up to 691 days	6.2% 2/32 • Up to 691 days
Nervous system disorders Headache	8.5% 5/59 • Up to 691 days	3.1% 1/32 • Up to 691 days
Nervous system disorders Partial seizures with secondary generalisation	5.1% 3/59 • Up to 691 days	0.00% 0/32 • Up to 691 days
Psychiatric disorders Anxiety	1.7% 1/59 • Up to 691 days	6.2% 2/32 • Up to 691 days
Respiratory, thoracic and mediastinal disorders Cough	5.1% 3/59 • Up to 691 days	3.1% 1/32 • Up to 691 days
Vascular disorders Hypertension	22.0% 13/59 • Up to 691 days	3.1% 1/32 • Up to 691 days

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER