Trial Outcomes & Findings for Bevacizumab With or Without Radiation Therapy in Treating Patients With Recurrent Glioblastoma (NCT NCT01730950)

NCT ID: NCT01730950

Last Updated: 2022-12-29

Results Overview

Survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times will be compared between the arms, which is reported in the statistical analysis results. Eighteen-month rates are provided. Analysis was planned to occur when 135 deaths were reported.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 182 participants
• Primary outcome timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.
• Results posted on: 2022-12-29

Participant Flow

Participant milestones

Measure	Bevacizumab Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT Radiation therapy (35Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.
Overall Study STARTED	90	92
Overall Study Eligible Population	84	86
Overall Study Adverse Event Population	76	83
Overall Study Response Population	78	77
Overall Study 6-month Progression-free Analysis	79	81
Overall Study Delayed Toxicity Population	0	83
Overall Study COMPLETED	84	86
Overall Study NOT COMPLETED	6	6

Reasons for withdrawal

Measure	Bevacizumab Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT Radiation therapy (35Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.
Overall Study Protocol Violation	6	6

Baseline Characteristics

Bevacizumab With or Without Radiation Therapy in Treating Patients With Recurrent Glioblastoma

Baseline characteristics by cohort

Measure	Bevacizumab n=84 Participants Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT n=86 Participants Radiation therapy (35Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Total n=170 Participants Total of all reporting groups
Age, Continuous	57 years n=5 Participants	60 years n=7 Participants	59 years n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	43 Participants n=7 Participants	81 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	43 Participants n=7 Participants	89 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 Participants n=5 Participants	81 Participants n=7 Participants	153 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	66 Participants n=5 Participants	75 Participants n=7 Participants	141 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Karnofsky Performance Status 60	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Karnofsky Performance Status 70-80	42 Participants n=5 Participants	41 Participants n=7 Participants	83 Participants n=5 Participants
Karnofsky Performance Status 90-100	39 Participants n=5 Participants	37 Participants n=7 Participants	76 Participants n=5 Participants
Neurologic Function No symptoms	21 Participants n=5 Participants	24 Participants n=7 Participants	45 Participants n=5 Participants
Neurologic Function Minor symptoms	40 Participants n=5 Participants	36 Participants n=7 Participants	76 Participants n=5 Participants
Neurologic Function Moderate symptoms (fully active)	17 Participants n=5 Participants	15 Participants n=7 Participants	32 Participants n=5 Participants
Neurologic Function Moderate symptoms (required assistance)	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Neurologic Function Severe symptoms	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Surgery for Initial Brain Tumor Biopsy only	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Surgery for Initial Brain Tumor Subtotal resection	20 Participants n=5 Participants	25 Participants n=7 Participants	45 Participants n=5 Participants
Surgery for Initial Brain Tumor Gross total resection	56 Participants n=5 Participants	52 Participants n=7 Participants	108 Participants n=5 Participants
Surgery for Initial Brain Tumor Other	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Recent Resection No / biopsy only	49 Participants n=5 Participants	57 Participants n=7 Participants	106 Participants n=5 Participants
Recent Resection Yes	35 Participants n=5 Participants	29 Participants n=7 Participants	64 Participants n=5 Participants
Histologic Tumor Type Glioblastoma (WHO Grade IV)	79 Participants n=5 Participants	82 Participants n=7 Participants	161 Participants n=5 Participants
Histologic Tumor Type Gliosarcoma	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Histologic Tumor Type Other	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.

Population: Eligible participants

Survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times will be compared between the arms, which is reported in the statistical analysis results. Eighteen-month rates are provided. Analysis was planned to occur when 135 deaths were reported.

Outcome measures

Measure	Bevacizumab n=84 Participants Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT n=86 Participants Radiation therapy (35 Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.
Overall Survival	25.1 percentage of participants Interval 15.2 to 35.0	21.6 percentage of participants Interval 12.1 to 31.1

SECONDARY outcome

Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.

Population: Eligible participants with response evaluations

Best observed objective response determined by serial measures of the product of the two largest perpendicular cross-sectional diameters using MacDonald Criteria:

• Complete Response (CR): complete disappearance of measurable enhancing lesion sustained ≥ 4 weeks; and no new lesions; and no corticosteroids.
• Partial Response (PR): ≥ 50% decrease from baseline in sum of products of the measurable enhancing lesion sustained ≥ 4 weeks; and no new lesions; and stable/reduced corticosteroid dose.
• Progression (P): ≥ 25% increase in sum of products of enhancing lesions (patient has not had steroid dose decreased since the last evaluation period); or any new lesions. A concomitant decrease in steroid dose rules out progression designation during initial 12 weeks after radiotherapy.
• Stable Disease (SD): all of following: does not qualify for CR, PR, or P; receiving stable/decreasing doses of steroids.

Estimated using an exact binomial distribution.

Outcome measures

Measure	Bevacizumab n=78 Participants Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT n=77 Participants Radiation therapy (35 Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.
Percentage of Participants With Complete or Partial Best Response	20.5 percentage of participants Interval 12.2 to 31.2	29.9 percentage of participants Interval 20.0 to 41.4

SECONDARY outcome

Timeframe: From randomization to six months

Population: Eligible participants with data at six months

Best observed objective response determined by serial measures of the product of the two largest perpendicular cross-sectional diameters using MacDonald Criteria:

Progression (P): ≥ 25% increase in sum of products of enhancing lesions (patient has not had steroid dose decreased since the last evaluation period); or any new lesions. A concomitant decrease in steroid dose rules out progression designation during initial 12 weeks after radiotherapy. Progression-free at 6 months means patient alive without progression at 6 months.

Outcome measures

Measure	Bevacizumab n=79 Participants Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT n=81 Participants Radiation therapy (35 Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.
Percentage of Participants Progression-free at 6 Months	29.1 percentage of participants Interval 19.4 to 40.4	54.3 percentage of participants Interval 42.9 to 65.4

SECONDARY outcome

Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.

Population: Eligible participants

Progression using using MacDonald Criteria is defined as ≥ 25% increase from baseline in sum of products of the two largest perpendicular cross-sectional diameters of enhancing lesions (patient has not had steroid dose decreased since the last evaluation period); or any new lesions. A concomitant decrease in steroid dose rules out progression designation during initial 12 weeks after radiotherapy. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times will be compared between the arms, which is reported in the statistical analysis results. Eighteen-month rates are provided. Analysis was planned to occur when 135 deaths were reported.

Outcome measures

Measure	Bevacizumab n=84 Participants Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT n=86 Participants Radiation therapy (35 Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.
Progression-free Survival	8.9 percentage of participants Interval 2.6 to 15.2	7.9 percentage of participants Interval 1.9 to 13.9

SECONDARY outcome

Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.

Population: Eligible participants on the radiation therapy arm who started radiation therapy

Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.

Outcome measures

Measure	Bevacizumab n=83 Participants Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT Radiation therapy (35 Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.
Percentage of Participants With Grade 3+ Central Nervous System (CNS) Toxicity Within 90 Days of Start of Radiation Therapy Reported as Possibly/Probably/Definitely Related to Protocol Treatment	4.8 percentage of participants Interval 1.3 to 11.9	—

SECONDARY outcome

Timeframe: From 91 days after the start of radiation therapy to end of follow-up. Maximum follow-up at the time of analysis is 58.2 months.

Population: Eligible participants on the radiation therapy arm who started radiation therapy and were alive at least 91 days from the start of radiation therapy

Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Estimated using an exact binomial distribution together with 95% confidence interval. The difference between the two groups will be tested using a chi square test.

Outcome measures

Measure	Bevacizumab n=83 Participants Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT Radiation therapy (35 Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.
Number of Participants With Grade 3+ CNS Toxicity More Than 90 Days of Start of Radiation Therapy Reported as Possibly/Probably/Definitely Related to Protocol Treatment	0 Participants	—

Adverse Events

Bevacizumab

Serious events: 27 serious events

Other events: 70 other events

Deaths: 4 deaths

Bevacizumab + RT

Serious events: 29 serious events

Other events: 73 other events

Deaths: 8 deaths

Serious adverse events

Measure	Bevacizumab n=76 participants at risk Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT n=83 participants at risk Radiation therapy (35Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.
Blood and lymphatic system disorders Anemia	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Cardiac disorders Sinus bradycardia	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Eye disorders Blurred vision	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Colonic obstruction	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Colonic perforation	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Nausea	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Vomiting	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Death NOS	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Edema limbs	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Fatigue	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders General disorders and administration site conditions - Other	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Neck edema	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Non-cardiac chest pain	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Pain	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Sudden death NOS	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Hepatobiliary disorders Cholecystitis	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Infections and infestations Infections and infestations - Other	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Infections and infestations Lung infection	2.6% 2/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Infections and infestations Sepsis	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Infections and infestations Urinary tract infection	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Infections and infestations Wound infection	2.6% 2/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Injury, poisoning and procedural complications Fall	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Injury, poisoning and procedural complications Wound dehiscence	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Investigations Investigations - Other	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Alkalosis	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Dehydration	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Hypokalemia	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Hyponatremia	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Back pain	2.6% 2/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	3.6% 3/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Musculoskeletal deformity	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Cerebrospinal fluid leakage	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Cognitive disturbance	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Encephalopathy	3.9% 3/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Headache	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Intracranial hemorrhage	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Seizure	6.6% 5/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	8.4% 7/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Stroke	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Syncope	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Tremor	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Psychiatric disorders Confusion	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Renal and urinary disorders Proteinuria	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Skin and subcutaneous tissue disorders Alopecia	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Vascular disorders Hematoma	2.6% 2/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Vascular disorders Hypertension	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Vascular disorders Hypotension	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Vascular disorders Thromboembolic event	2.6% 2/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Vascular disorders Vasculitis	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	0.00% 0/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.

Other adverse events

Measure	Bevacizumab n=76 participants at risk Bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.	Bevacizumab + RT n=83 participants at risk Radiation therapy (35Gy in 10 fractions of 3.5 Gy) with bevacizumab (IV 10mg/kg) every 2 weeks until disease progression.
Musculoskeletal and connective tissue disorders Back pain	6.6% 5/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	9.6% 8/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Blood and lymphatic system disorders Anemia	15.8% 12/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	12.0% 10/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	9.2% 7/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Eye disorders Blurred vision	11.8% 9/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	12.0% 10/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Eye disorders Eye disorders - Other	6.6% 5/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	8.4% 7/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Abdominal pain	6.6% 5/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	3.6% 3/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Constipation	15.8% 12/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	9.6% 8/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Diarrhea	13.2% 10/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	14.5% 12/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Dyspepsia	6.6% 5/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	4.8% 4/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Nausea	26.3% 20/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	16.9% 14/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Gastrointestinal disorders Vomiting	9.2% 7/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	8.4% 7/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Edema limbs	19.7% 15/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	10.8% 9/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Fatigue	44.7% 34/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	56.6% 47/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Gait disturbance	18.4% 14/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	19.3% 16/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders General disorders and administration site conditions - Other	7.9% 6/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
General disorders Pain	13.2% 10/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	14.5% 12/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Infections and infestations Infections and infestations - Other	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	6.0% 5/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Infections and infestations Urinary tract infection	7.9% 6/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	9.6% 8/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Injury, poisoning and procedural complications Bruising	6.6% 5/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	4.8% 4/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Injury, poisoning and procedural complications Fall	10.5% 8/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	7.2% 6/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Investigations Alanine aminotransferase increased	9.2% 7/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	13.3% 11/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Investigations Aspartate aminotransferase increased	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	7.2% 6/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Investigations Lymphocyte count decreased	14.5% 11/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	8.4% 7/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Investigations Neutrophil count decreased	10.5% 8/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	4.8% 4/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Investigations Platelet count decreased	27.6% 21/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	14.5% 12/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Investigations Weight loss	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	9.6% 8/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Investigations White blood cell decreased	11.8% 9/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	8.4% 7/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Anorexia	10.5% 8/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	12.0% 10/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Hyperglycemia	18.4% 14/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	14.5% 12/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Hypoalbuminemia	9.2% 7/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Hypocalcemia	7.9% 6/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	3.6% 3/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Hypokalemia	9.2% 7/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	3.6% 3/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Metabolism and nutrition disorders Hyponatremia	6.6% 5/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	7.2% 6/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	9.6% 8/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	11.8% 9/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	6.0% 5/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	10.5% 8/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	6.0% 5/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	7.9% 6/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	6.0% 5/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	6.0% 5/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	3.6% 3/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	7.9% 6/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	3.6% 3/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Myalgia	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	4.8% 4/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Musculoskeletal and connective tissue disorders Pain in extremity	7.9% 6/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	3.6% 3/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Ataxia	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Cognitive disturbance	10.5% 8/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	4.8% 4/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Dizziness	15.8% 12/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	15.7% 13/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Dysarthria	6.6% 5/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	4.8% 4/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Dysphasia	23.7% 18/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	13.3% 11/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Headache	48.7% 37/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	37.3% 31/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Lethargy	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	1.2% 1/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Memory impairment	15.8% 12/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	20.5% 17/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Nervous system disorders - Other	13.2% 10/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	9.6% 8/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Paresthesia	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	6.0% 5/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Peripheral sensory neuropathy	10.5% 8/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	3.6% 3/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Nervous system disorders Seizure	14.5% 11/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	16.9% 14/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Psychiatric disorders Anxiety	17.1% 13/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	9.6% 8/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Psychiatric disorders Confusion	14.5% 11/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	14.5% 12/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Psychiatric disorders Depression	10.5% 8/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	10.8% 9/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Psychiatric disorders Insomnia	11.8% 9/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	14.5% 12/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Renal and urinary disorders Hematuria	3.9% 3/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	8.4% 7/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Renal and urinary disorders Proteinuria	21.1% 16/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	24.1% 20/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Renal and urinary disorders Renal and urinary disorders - Other	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	3.6% 3/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Renal and urinary disorders Urinary incontinence	9.2% 7/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	4.8% 4/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	6.6% 5/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	3.6% 3/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Respiratory, thoracic and mediastinal disorders Cough	10.5% 8/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	18.1% 15/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	9.2% 7/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	10.8% 9/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.3% 1/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	9.6% 8/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Respiratory, thoracic and mediastinal disorders Hoarseness	7.9% 6/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	7.2% 6/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Skin and subcutaneous tissue disorders Alopecia	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	13.3% 11/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Skin and subcutaneous tissue disorders Dry skin	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	6.0% 5/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Skin and subcutaneous tissue disorders Pruritus	6.6% 5/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Skin and subcutaneous tissue disorders Rash acneiform	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	2.4% 2/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	3.9% 3/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	6.0% 5/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	5.3% 4/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	8.4% 7/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Vascular disorders Hypertension	43.4% 33/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	34.9% 29/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.
Vascular disorders Thromboembolic event	7.9% 6/76 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.	4.8% 4/83 • Adverse events were to be reported every 2 months for first year, every 6 months for second year, then annually until study completion. Maximum follow-up at time of analysis was 52.8 months.

Additional Information

Wendy Seiferheld

NRG Oncology

Phone: 215-574-3208

Email: seiferheldw@nrgoncology.org

Results disclosure agreements

• Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
• Publication restrictions are in place

Restriction type: OTHER