Weekly vs. Every 2 Week vs. Every 3 Week Administration o... | NCT00281528

Label	Type	Description	Intervention Names
260 mg/m^2 ABI-007 every 3 weeks	Experimental	260 mg/m^2 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks	Drug: ABI-007 (Abraxane) Drug: bevacizumab
260 mg/m^2 ABI-007 every 2 weeks	Experimental	260 mg/m^2 ABI-007 every 2 weeks and 10 mg/kg bevacizumab every 2 weeks	Drug: ABI-007 (Abraxane) Drug: bevacizumab
130 mg/m^2 ABI-007 weekly	Experimental	130 mg/m^2 ABI-007 weekly (without a week of 'rest') and 10 mg/kg bevacizumab every 2 weeks	Drug: ABI-007 (Abraxane) Drug: bevacizumab

Name	Type	Description	Arm Group Labels	Other Names
ABI-007 (Abraxane)	Drug	30 minute infusions	130 mg/m^2 ABI-007 weekly 260 mg/m^2 ABI-007 every 2 weeks 260 mg/m^2 ABI-007 every 3 weeks

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Percentage of Participants Confirmed Complete Response (CR) or Partial Response (PR) Based on Response Evaluation Criteria In Solid Tumors (RECIST v1.0)	Using the RECIST response criteria version 1.0, the percent of participants achieving either a complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions based on confirmed responses from the investigator assessment of best overall response during study treatment.	Up to 43 months
Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC) as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) ANC counts were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 75.010^9L; Grade 2 = <1.5 - 1.010^9L; Grade 3 = <1.0 - 0.510^9L; Grade 4 = <0.510^9L	up to 54 months
Participant Counts of the Most Severe Grade for White Blood Cells (WBC) as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) WBC counts were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal -3.010^9/L; Grade 2 = <3.0 - 2.010^9/L; Grade 3 = <2.0 - 1.010^9/L; Grade 4 = <1.010^9/L	up to 54 months
Participant Counts of the Most Severe Grade for Platelet Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)	Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) platelet counts were graded using NCI CTCAE version 3: Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 75.010^9/L; Grade 2 = <75.0 - 50.010^9/L; Grade 3 = <50.0 - 25.010^9/L; Grade 4 = <25.010^9/L

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response (i.e., Total Response) Based on Response Evaluation Criteria In Solid Tumors (RECIST v1.0)	Using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), the percentage of participants achieving either A complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or A partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions or Stable disease (SD) defined as neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for progressive disease.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Pathologically confirmed adenocarcinoma of the breast.
Stage IV disease
Measurable disease
Patients must not be a candidate for Herceptin therapy
At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be pathologic proof of progressive disease within the radiation portal.
At least 4 weeks since major surgery, with full recovery.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Female >18 years of age.
Patient has the following blood counts at Baseline:

Absolute neutrophil count ≥ 1.5 x 10^9cells/L; platelets ≥ 100 x 10^9 cells/L; hemoglobin ≥ 9 g/dL.

Patient has the following blood chemistry levels at Baseline: Aspartate transaminase (AST or SGOT), alanine aminotransferase (ALT or SGPT) ≤ 2.5x upper limit of normal range (ULN); total bilirubin ≤ ULN; creatinine ≤ 1.5 mg/dL.
If female of childbearing potential, pregnancy test is negative within 72 hours of first dose of study drug.
If fertile, the patient agrees to use an effective method to avoid pregnancy for the duration of the study.
Informed consent has been obtained.

Exclusion Criteria:

Prior neo-adjuvant or adjuvant chemotherapy is allowed, and patients must have recovered from the acute toxicity of such therapies. No prior therapy for metastatic disease is allowed. If a taxane was part of the adjuvant regimen, at least 12 months should have passed from completion of taxane regimen to relapse. If a non-taxane-based adjuvant therapy was administered, at least 6 months should have passed from completion to relapse.
Concurrent immunotherapy or hormonal therapy.
Parenchymal brain metastases, including leptomeningeal involvement.
Inadequately controlled hypertension (defined as blood pressure of > 150/100 mmHg) or New York Heart Association (NYHA) Grade 2 or greater congestive heart failure.
Any prior history of hypertensive crisis or hypertensive encephalopathy.
History of myocardial infarction or unstable angina within 6 months prior to study enrollment.
History of stroke or transient ischemic attack within 6 months prior to study enrollment.
Significant vascular disease (e.g., aortic aneurysm, aortic dissection).
Symptomatic peripheral vascular disease.
Evidence of bleeding diathesis or coagulopathy.
History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to study enrollment.
Proteinuria at screening as demonstrated by either: - Urine protein:creatinine (UPC) ratio > 1.0 at screening OR - Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
Known hypersensitivity to any component of bevacizumab.
Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to first dose.
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first dose, anticipation of need for major surgical procedure during the course of the study. Serious, non-healing wound, ulcer, or bone fracture. Serious intercurrent medical or psychiatric illness, including serious active infection.
History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer.
Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
Pregnant or nursing women.
Sensory neuropathy of > Grade 1 at baseline.

Name	Affiliation	Role
Andrew Seidman, MD	Memorial Sloan Kettering Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Division of Hematology/Oncology University of Alabama at Birmingham		Birmingham	Alabama		United States

PubMed Identifier	Type	Citation	Retractions
23829890	Background	Seidman AD, Conlin AK, Bach A, Moynahan ME, Lake D, Forero A, Wright GS, Hackney MH, Clawson A, Norton L, Hudis CA. Randomized phase II trial of weekly vs. every 2 weeks vs. every 3 weeks nanoparticle albumin-bound paclitaxel with bevacizumab as first-line chemotherapy for metastatic breast cancer. Clin Breast Cancer. 2013 Aug;13(4):239-246.e1. doi: 10.1016/j.clbc.2013.02.008.
20705560

ID	Title	Description
FG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
FG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Percentage of Participants Confirmed Complete Response (CR) or Partial Response (PR) Based on Response Evaluation Criteria In Solid Tumors (RECIST v1.0)

Using the RECIST response criteria version 1.0, the percent of participants achieving either a complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions based on confirmed responses from the investigator assessment of best overall response during study treatment.

Treated population

Posted

Number

Percent of Total Participants

Up to 43 months

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Units	Counts
Participants	OG00075 OG00154 OG00279

Title

Denominators

Categories

Title	Measurements
	OG00041 OG00143 OG00247

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002		Cochran-Mantel-Haenszel	Stratified by study site	0.4476	Group comparison was performed between group 260 mg/m^2 ABI-007 every 3 weeks and group 130 mg/m^2 ABI-007 weekly, as based on amended protocol, no type I error adjustment for multiplicity; a priori threshold for statistical significance is 0.05.						95							Superiority or Other (legacy)

Secondary

Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response (i.e., Total Response) Based on Response Evaluation Criteria In Solid Tumors (RECIST v1.0)

Using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), the percentage of participants achieving either

A complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or
A partial response (PR) defined as at least a 30% decrease in the sum of the longest diameters of target lesions and no progression in non-target lesions or
Stable disease (SD) defined as neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for progressive disease.

Treated population

Posted

Number

Percent of Total Participants

Up to 43 months (until progressed)

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Primary

Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC) as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)

Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) ANC counts were graded using NCI CTCAE version 3:

Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 75.0*10^9L; Grade 2 = <1.5 - 1.0*10^9L; Grade 3 = <1.0 - 0.5*10^9L; Grade 4 = <0.5*10^9L

Treated population who had at least one post baseline value

Posted

Number

participants

up to 54 months

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Secondary

Kaplan Meier Estimate for Time to Disease Progression (TTP)

Time to progression was defined as the time from the first dose of study drug to the start of progression. Participants that did not have progression were censored at the last known time the patient was evaluated for progression. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

Treated population

Posted

Median

95% Confidence Interval

Months

Up to 43 months (until progressed)

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Secondary

Kaplan Meier Estimate for Duration of Response

Duration of response was defined as the time from response to the time of disease progression for participants who achieve an objective confirmed complete (CR) or partial overall response (PR). Disease progression is based on the assessments by the investigator. Participants who did not have disease progression following a confirmed complete or partial target response were censored at the last known time that the participant was evaluated for response

Treated population who achieved a complete or partial response

Posted

Median

95% Confidence Interval

Months

Up to 43 months (until progressed)

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Secondary

Kaplan Meier Estimate for Participant Survival

Participant survival was summarized using Kaplan-Meier estimate of the time of first dose of study drug to the last known time that the participant was alive. Participants that were alive at the end of follow-up would be censored at the last known time that the patient was alive.

Treated population

Posted

Median

95% Confidence Interval

Months

Up to 56 months

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Units	Counts
Participants

Primary

Participant Counts of the Most Severe Grade for White Blood Cells (WBC) as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)

Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) WBC counts were graded using NCI CTCAE version 3:

Grade 0 = within normal limits; Grade 1 = < lower limit of normal -3.0*10^9/L; Grade 2 = <3.0 - 2.0*10^9/L; Grade 3 = <2.0 - 1.0*10^9/L; Grade 4 = <1.0*10^9/L

Treated population who had at least one post baseline value

Posted

Number

participants

up to 54 months

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Primary

Participant Counts of the Most Severe Grade for Platelet Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)

Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) platelet counts were graded using NCI CTCAE version 3:

Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 75.0*10^9/L; Grade 2 = <75.0 - 50.0*10^9/L; Grade 3 = <50.0 - 25.0*10^9/L; Grade 4 = <25.0*10^9/L

Treated population who had at least one post baseline value

Posted

Number

participants

up to 54 months

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Primary

Participant Counts of the Most Severe Grade for Hemoglobin Levels as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)

Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) hemoglobin levels were graded using NCI CTCAE version 3:

Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 100g/L; Grade 2 = <100 - 80g/L; Grade 3 = <80 - 65g/L; Grade 4 = <65g/L

Treated population who had at least one post baseline value

Posted

Number

participants

up to 54 months

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Primary

The Number of Participants With at Least One Dose Reduction for ABI-007

Participants with at least one dose reduction for ABI-007. ABI-007 (Abraxane) dose could be reduced according to protocol guidelines if the participant was experiencing toxicities. Participants were allowed two ABI-007 (Abraxane) dose reductions during the course of the trial. This outcome is considered to be both a safety and an efficacy outcome.

Treated population

Posted

Number

Participants

Up to 53 months

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Units	Counts

Primary

The Number of Participants With at Least One Dose Delay for ABI-007

Participants with at least one dose delay for ABI-007. Treatment delays of no longer than 2 weeks allowed participants to recovery from acute toxicity. If treatment was delayed beyond 2 weeks, continuing treatment on protocol was at the physician's discretion, based upon the best interests of the participant. This outcome is considered to be both a safety and an efficacy outcome.

Treated population

Posted

Number

Participants

Up to 53 months

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Units	Counts

Primary

The Number of Participants With a Dose Interruption of ABI-007

Number of participants who interrupted (omitted) a dose at some point in the treatment period. This outcome is considered to be both a safety and an efficacy outcome.

Treated population

Posted

Number

Participants

Up to 53 months

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Units	Counts
Participants

Secondary

Kaplan Meier Estimate for Progression-Free Survival (PFS)

PFS was defined as the time from the first dose of study drug to the start of progression or patient death (any cause) whichever occurred first. Participants that did not have progression or have not died were censored at the last known time the participant was progression free. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

Treated population

Posted

Median

95% Confidence Interval

months

up to 56 months

ID	Title	Description
OG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
OG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
OG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks

Units

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.0	Non-systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0022 events2 affected79 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 10.0	Non-systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Arrhythmia	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Colitis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0023 events3 affected79 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Ileus	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0011 events1 affected54 at risk EG0024 events4 affected79 at risk
Asthenia	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0022 events1 affected79 at risk
Catheter site pain	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Chest pain	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Fatigue	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0021 events1 affected79 at risk
Gait disturbance	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Mucosal inflammation	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0022 events2 affected79 at risk
Pyrexia	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0022 events2 affected79 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Appendicitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Breast cellulitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Cellulitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Diverticulitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0022 events2 affected79 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Pneumonia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Sepsis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0021 events1 affected79 at risk
Urinary tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Hepatic enzyme increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected75 at risk EG0012 events2 affected54 at risk EG0025 events5 affected79 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Polyarthritis	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Coordination abnormal	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Cranial neuropathy	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Dysgeusia	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Headache	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Neuropathy	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0012 events2 affected54 at risk EG0022 events2 affected79 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Confusional state	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Major depression	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Venous thrombosis limb	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Haematoma	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0020 events0 affected79 at risk
Hypertension	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0020 events0 affected79 at risk
Thrombosis	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0012 events1 affected54 at risk EG0020 events0 affected79 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected75 at risk EG0011 events1 affected54 at risk EG0022 events2 affected79 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG00024 events15 affected75 at risk EG00132 events20 affected54 at risk EG00237 events24 affected79 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG00032 events6 affected75 at risk EG0017 events4 affected54 at risk EG00223 events11 affected79 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG00052 events18 affected75 at risk EG00113 events9 affected54 at risk EG00263 events31 affected79 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0012 events2 affected54 at risk EG0025 events5 affected79 at risk
Dry eye	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0005 events5 affected75 at risk EG0010 events0 affected54 at risk EG0026 events4 affected79 at risk
Lacrimation increased	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0003 events3 affected75 at risk EG0015 events5 affected54 at risk EG00222 events14 affected79 at risk
Vision blurred	Eye disorders	MedDRA 10.0	Systematic Assessment	EG00010 events9 affected75 at risk EG00110 events9 affected54 at risk EG00213 events11 affected79 at risk
Visual disturbance	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0005 events4 affected75 at risk EG0012 events1 affected54 at risk EG0024 events4 affected79 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 events3 affected75 at risk EG0015 events3 affected54 at risk EG0025 events5 affected79 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00016 events9 affected75 at risk EG0012 events2 affected54 at risk EG00212 events11 affected79 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0006 events4 affected75 at risk EG0011 events1 affected54 at risk EG00210 events9 affected79 at risk
Constipation	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00041 events30 affected75 at risk EG00129 events28 affected54 at risk EG00254 events38 affected79 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00042 events24 affected75 at risk EG00136 events24 affected54 at risk EG00262 events43 affected79 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 events4 affected75 at risk EG0014 events3 affected54 at risk EG0026 events5 affected79 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00013 events11 affected75 at risk EG0013 events2 affected54 at risk EG0026 events6 affected79 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 events4 affected75 at risk EG0013 events3 affected54 at risk EG0023 events3 affected79 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected75 at risk EG0011 events1 affected54 at risk EG0028 events8 affected79 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0012 events1 affected54 at risk EG0025 events5 affected79 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 events3 affected75 at risk EG0012 events2 affected54 at risk EG0026 events6 affected79 at risk
Hypoaesthesia oral	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0014 events4 affected54 at risk EG0023 events2 affected79 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00053 events37 affected75 at risk EG00153 events36 affected54 at risk EG00258 events40 affected79 at risk
Oral pain	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0014 events4 affected54 at risk EG0025 events4 affected79 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0011 events1 affected54 at risk EG0027 events6 affected79 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00014 events10 affected75 at risk EG0019 events8 affected54 at risk EG00218 events13 affected79 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00020 events16 affected75 at risk EG00125 events18 affected54 at risk EG00228 events21 affected79 at risk
Asthenia	General disorders	MedDRA 10.0	Systematic Assessment	EG0005 events4 affected75 at risk EG00113 events11 affected54 at risk EG00210 events8 affected79 at risk
Chest pain	General disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected75 at risk EG0015 events4 affected54 at risk EG0029 events7 affected79 at risk
Chills	General disorders	MedDRA 10.0	Systematic Assessment	EG0008 events6 affected75 at risk EG0014 events4 affected54 at risk EG00213 events11 affected79 at risk
Fatigue	General disorders	MedDRA 10.0	Systematic Assessment	EG000127 events55 affected75 at risk EG00182 events43 affected54 at risk EG002137 events64 affected79 at risk
Gait disturbance	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0012 events2 affected54 at risk EG0024 events4 affected79 at risk
Mucosal inflammation	General disorders	MedDRA 10.0	Systematic Assessment	EG00017 events14 affected75 at risk EG00115 events13 affected54 at risk EG00228 events16 affected79 at risk
Oedema	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0011 events1 affected54 at risk EG0026 events5 affected79 at risk
Oedema peripheral	General disorders	MedDRA 10.0	Systematic Assessment	EG00010 events6 affected75 at risk EG00111 events10 affected54 at risk EG00215 events11 affected79 at risk
Pain	General disorders	MedDRA 10.0	Systematic Assessment	EG0006 events6 affected75 at risk EG00113 events11 affected54 at risk EG00215 events11 affected79 at risk
Pyrexia	General disorders	MedDRA 10.0	Systematic Assessment	EG00010 events9 affected75 at risk EG00112 events11 affected54 at risk EG00219 events11 affected79 at risk
Hypersensitivity	Immune system disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0013 events3 affected54 at risk EG0020 events0 affected79 at risk
Cellulitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0028 events4 affected79 at risk
Nail infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0025 events4 affected79 at risk
Nasopharyngitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0012 events2 affected54 at risk EG0027 events5 affected79 at risk
Oral candidiasis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0013 events3 affected54 at risk EG0022 events2 affected79 at risk
Sinusitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0004 events4 affected75 at risk EG0013 events3 affected54 at risk EG0029 events7 affected79 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG00010 events9 affected75 at risk EG0015 events5 affected54 at risk EG0029 events9 affected79 at risk
Urinary tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG00021 events13 affected75 at risk EG00110 events9 affected54 at risk EG00213 events12 affected79 at risk
Haemoglobin decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected75 at risk EG0013 events3 affected54 at risk EG0024 events3 affected79 at risk
Weight decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0007 events4 affected75 at risk EG00111 events9 affected54 at risk EG0024 events4 affected79 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG00020 events16 affected75 at risk EG00126 events19 affected54 at risk EG00233 events24 affected79 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0004 events4 affected75 at risk EG0014 events4 affected54 at risk EG0026 events6 affected79 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0003 events3 affected75 at risk EG0011 events1 affected54 at risk EG0028 events7 affected79 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0016 events6 affected54 at risk EG0028 events7 affected79 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG00060 events26 affected75 at risk EG00124 events21 affected54 at risk EG00220 events16 affected79 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG00012 events12 affected75 at risk EG00110 events9 affected54 at risk EG00220 events11 affected79 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG00016 events14 affected75 at risk EG00122 events18 affected54 at risk EG0029 events6 affected79 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0004 events2 affected75 at risk EG0015 events5 affected54 at risk EG0027 events7 affected79 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0003 events2 affected75 at risk EG0013 events3 affected54 at risk EG0024 events4 affected79 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG00014 events11 affected75 at risk EG00114 events10 affected54 at risk EG00210 events10 affected79 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG00020 events14 affected75 at risk EG00116 events11 affected54 at risk EG00219 events14 affected79 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0013 events3 affected54 at risk EG0020 events0 affected79 at risk
Shoulder pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0005 events5 affected75 at risk EG0012 events2 affected54 at risk EG0028 events6 affected79 at risk
Coordination abnormal	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0005 events5 affected75 at risk EG0014 events1 affected54 at risk EG0023 events3 affected79 at risk
Dizziness	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00017 events15 affected75 at risk EG00110 events10 affected54 at risk EG00213 events11 affected79 at risk
Dysgeusia	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00016 events14 affected75 at risk EG00117 events14 affected54 at risk EG00236 events28 affected79 at risk
Headache	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00017 events15 affected75 at risk EG00114 events11 affected54 at risk EG00228 events18 affected79 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0003 events1 affected75 at risk EG0015 events3 affected54 at risk EG0024 events4 affected79 at risk
Neuropathy	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00096 events34 affected75 at risk EG00177 events24 affected54 at risk EG00294 events34 affected79 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00036 events15 affected75 at risk EG00112 events9 affected54 at risk EG00241 events13 affected79 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0002 events1 affected75 at risk EG0014 events3 affected54 at risk EG0026 events4 affected79 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG000104 events34 affected75 at risk EG00163 events24 affected54 at risk EG002111 events36 affected79 at risk
Anxiety	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0004 events4 affected75 at risk EG0017 events7 affected54 at risk EG0028 events8 affected79 at risk
Depression	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG00012 events12 affected75 at risk EG0019 events8 affected54 at risk EG00213 events11 affected79 at risk
Insomnia	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG00019 events17 affected75 at risk EG00118 events17 affected54 at risk EG00211 events10 affected79 at risk
Dysuria	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0005 events5 affected75 at risk EG0014 events4 affected54 at risk EG0024 events2 affected79 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected75 at risk EG0010 events0 affected54 at risk EG0025 events4 affected79 at risk
Proteinuria	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0005 events5 affected75 at risk EG0011 events1 affected54 at risk EG0024 events3 affected79 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0013 events3 affected54 at risk EG0021 events1 affected79 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG00024 events20 affected75 at risk EG0019 events8 affected54 at risk EG00226 events20 affected79 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG00010 events10 affected75 at risk EG0014 events4 affected54 at risk EG00213 events13 affected79 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG00013 events13 affected75 at risk EG00111 events9 affected54 at risk EG00227 events21 affected79 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG00044 events32 affected75 at risk EG00125 events23 affected54 at risk EG00253 events42 affected79 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 events3 affected75 at risk EG0013 events3 affected54 at risk EG0022 events2 affected79 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 events3 affected75 at risk EG00110 events8 affected54 at risk EG0029 events8 affected79 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0006 events4 affected75 at risk EG0014 events4 affected54 at risk EG0025 events4 affected79 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 events3 affected75 at risk EG0014 events4 affected54 at risk EG00211 events9 affected79 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00051 events49 affected75 at risk EG00145 events35 affected54 at risk EG00268 events53 affected79 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0007 events7 affected75 at risk EG0018 events8 affected54 at risk EG00212 events12 affected79 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0002 events2 affected75 at risk EG0016 events5 affected54 at risk EG0026 events5 affected79 at risk
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0004 events4 affected75 at risk EG0016 events5 affected54 at risk EG00211 events10 affected79 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0009 events9 affected75 at risk EG00111 events8 affected54 at risk EG00242 events23 affected79 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0015 events4 affected54 at risk EG0022 events2 affected79 at risk
Onychorrhexis	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0014 events3 affected54 at risk EG0023 events1 affected79 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0006 events5 affected75 at risk EG0014 events3 affected54 at risk EG0027 events7 affected79 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00023 events20 affected75 at risk EG00125 events17 affected54 at risk EG00242 events31 affected79 at risk
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 events0 affected75 at risk EG0012 events2 affected54 at risk EG0028 events7 affected79 at risk
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0002 events1 affected75 at risk EG0013 events3 affected54 at risk EG0024 events4 affected79 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0013 events3 affected54 at risk EG0029 events7 affected79 at risk
Hot flush	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0007 events5 affected75 at risk EG0015 events4 affected54 at risk EG0027 events7 affected79 at risk
Hypertension	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG00027 events19 affected75 at risk EG0019 events9 affected54 at risk EG00217 events11 affected79 at risk
Lymphoedema	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0011 events1 affected54 at risk EG00212 events8 affected79 at risk
Ear infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 events1 affected75 at risk EG0010 events0 affected54 at risk EG0024 events4 affected79 at risk
Blood pressure increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0004 events4 affected75 at risk EG0010 events0 affected54 at risk EG0021 events1 affected79 at risk

ID	Term
D001943	Breast Neoplasms
D009362	Neoplasm Metastasis

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000068196	Albumin-Bound Paclitaxel
D000068258	Bevacizumab

ID	Term
D017239	Paclitaxel
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D000418	Albumins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.
BG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks
BG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	260 mg/m^2 ABI-007 Every 3 Weeks	260 mg/m^2 of ABI-007 every 3 weeks and 15 mg/kg bevacizumab every 3 weeks.	22	75	75	75
EG001	260 mg/m^2 ABI-007 Every 2 Weeks	260 mg/m^2 of ABI-007 every two weeks and 10 mg/kg bevacizumab every 2 weeks	16	54	54	54
EG002	130 mg/m^2 ABI-007 Weekly	130 mg/m^2 of ABI-007 every week and 10 mg/kg bevacizumab every 2 weeks	32	79	78	79