Combination Chemotherapy and Paclitaxel Plus Trastuzumab... | NCT00513292

ID	Type	Description	Link
NCI-2009-00341	Registry Identifier	CTRP (Clinical Trial Reporting Program)
CDR0000559039
ACOSOG-Z1041
Z1041	Other Identifier	American College of Surgeons Oncology Group
ACOSOG-Z1041	Other Identifier	CTEP
U10CA012027	U.S. NIH Grant/Contract		View source

Description Module

Detailed Description

PRIMARY OBJECTIVES:

I. The primary objective of this study is to compare the pathologic complete response rate (pCR) within the breast of a sequential regimen of concurrent weekly paclitaxel and trastuzumab, followed by continued weekly trastuzumab administered concurrently with FEC-75 (Arm 2), to the pCR rate of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab (Arm 1).

SECONDARY OBJECTIVES:

I. To estimate the cardiotoxicity of a sequential regimen of concurrent weekly paclitaxel and trastuzumab, followed by continued weekly trastuzumab administered concurrently with FEC-75, followed postoperatively by q 3 week trastuzumab for a total duration of trastuzumab therapy through 52 weeks from the first dose (Arm 2), and compare the cardiotoxicity to that of a sequential regimen of FEC-75 alone followed by concurrent weekly paclitaxel and trastuzumab, followed by q 3 week trastuzumab for a total duration of trastuzumab therapy through 52 weeks from the first dose (Arm 1).

II. To compare the combined pCR rate in the breast and ipsilateral axilla obtained with the two regimens evaluated in this study.

III. To compare the clinical response rates (cRR) of the two regimens evaluated in this study.

IV. To compare the non-cardiac toxicity of the two regimens evaluated in this study.

V. To compare breast conservation rates achieved with the two regimens evaluated in this study.

VI. To evaluate disease-free survival and overall survival at 5 years post-randomization.

VII. To correlate pCR rate with potential molecular markers of response.

OUTLINE: Patients are stratified by clinical tumor size (breast tumor size < 2 cm and nodal metastases < 2 cm vs breast tumor size < 2 cm and nodal metastases ≥ 2 cm vs breast tumor size 2-4 cm [any nodal status] vs breast tumor size ≥ 4 cm [any nodal status]), age (< 50 vs ≥ 50) and hormone receptor status (estrogen receptor [ER]- and progesterone receptor [PgR]-negative vs ER- and/or PgR-positive). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive FEC comprising fluoroucacil intravenously (IV), epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks.

ARM II: Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after completion of paclitaxel and trastuzumab, patients receive FEC comprising fluoroucacil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I.

After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for 4 years.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
FEC-75 then Paclitaxel/trastuzumab	Active Comparator	Patients receive FEC comprising fluoroucacil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks.	Drug: Cyclophosphamide Drug: Epirubicin Hydrochloride Other: Laboratory Biomarker Analysis Drug: Paclitaxel Procedure: Therapeutic Conventional Surgery Biological: Trastuzumab
Paclitaxel/trastuzumab then trastuzumab/FEC-75	Experimental	Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluoroucacil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I.	Drug: Cyclophosphamide Drug: Epirubicin Hydrochloride Other: Laboratory Biomarker Analysis Drug: Paclitaxel Procedure: Therapeutic Conventional Surgery Biological: Trastuzumab

Name	Type	Description	Arm Group Labels	Other Names
Cyclophosphamide	Drug	Given IV	FEC-75 then Paclitaxel/trastuzumab Paclitaxel/trastuzumab then trastuzumab/FEC-75

Measure	Description	Time Frame
pCR Within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapy	Pathological complete response (pCR) rates will be based on institutional pathology reports. In the final analysis for publication, rates will be based on blinded central review of these institutional pathology reports. The Chi-squared test will be conducted at the two-sided 0.05 level. A 95% confidence interval will be computed for the difference in pCR rates.	Up to 5 years

Measure	Description	Time Frame
Combined pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy	pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy (among those with Metastasis to movable ipsilateral axillary lymph node(s) (cN1-3) disease).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of invasive adenocarcinoma by core needle biopsy
- Fine needle aspiration allowed provided primary tumor size < 2 cm and lymph node metastases are present
- Excisional biopsy of the primary tumor allowed provided biopsy-positive lymph nodes are present
Primary tumor ≥ 2 cm and/or ≥ 1 biopsy-positive lymph node
HER2-positive disease
- Confirmation by fluorescent in situ hybridization (FISH) requires gene amplification
- Confirmation by immunohistochemistry (IHC) requires a strongly positive (3+) staining intensity score
Ductal carcinoma in situ (DCIS) or synchronous DCIS of the contralateral breast regardless of prior therapy allowed
- Synchronous invasive breast cancer not allowed
Ipsilateral DCIS treated by local excision with or without hormonal therapy allowed
- Those treated with radiation therapy are not allowed
No definitive clinical or radiologic evidence of metastatic disease
No history of invasive breast cancer
Hormone receptor status known
Menopausal status not specified
ECOG performance status of 0 -1
Absolute neutrophil count ≥ 1,200/mm³
Platelet count ≥ 100,000/mm³
Total bilirubin normal unless the patient has a grade 1 bilirubin elevation (normal to 1.5 times upper limit of normal [ULN]) resulting from Gilbert disease or similar syndrome due to slow conjugation of bilirubin
Alkaline phosphatase ≤ 2.5 times ULN
AST ≤ 1.5 times ULN
Creatinine normal
Left ventricular ejection fraction (LVEF) ≥ 55 by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) within the past 3 months
Patients with either skeletal pain or alkaline phosphatase that is > ULN but ≤ 2.5 times ULN allowed if bone scans fail to demonstrate metastatic disease
- Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy
Prior non-breast malignancies allowed if disease-free for 5 years since completion of initial treatment regimen and deemed by their physician to be at low risk for recurrence
- Patients who had the following cancers are eligible if diagnosed and treated within the past 5 years:
  - Carcinoma in situ of the cervix
  - Colon carcinoma in situ
  - Melanoma in situ
  - Basal cell and squamous cell carcinoma of the skin
No cardiac disease that would preclude the use of epirubicin hydrochloride or trastuzumab (Herceptin®) including any of the following:
- Active cardiac disease
- Angina pectoris that requires the use of antianginal medication
- Cardiac arrhythmia requiring medication
- Severe conduction abnormality
- Clinically significant valvular disease
- Cardiomegaly on chest x-ray
- Ventricular hypertrophy on EKG
- Patient's with poorly controlled hypertension ( i.e., diastolic greater than 100 mm/Hg)
  - Patients with hypertension that is well controlled on medication are eligible
- History of cardiac disease
- Myocardial infarction documented as a clinical diagnosis or by EKG or any other tests
- Documented congestive heart failure
- Documented cardiomyopathy
No sensory or motor neuropathy ≥ grade 2, as defined by the NCI's CTCAE v3.0
Women of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy
Women of child bearing potential must have a negative urine or serum pregnancy test within 2 weeks of registration
Not pregnant or nursing
No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements
No non-malignant systemic disease (e.g., cardiovascular, renal, hepatic) that would preclude treatment with either of the treatment regimens
No prior surgical axillary staging procedure
- Prior non-excisional biopsy of an axillary node allowed
No prior treatment for this breast cancer
- Hormonal therapy allowed if had been given for up to a total of 28 days anytime after diagnosis and before study entry
- Hormonal therapy must stop at or before study entry and be re-started, if indicated, following surgery
No prior therapy with anthracyclines or taxanes for any malignancy
No other investigational agents within the past 30 days
No concurrent sex hormonal therapy (e.g., birth control pills, ovarian hormonal replacement therapy)
No concurrent therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention

Name	Affiliation	Role
Aman Buzdar	American College of Surgeons	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of South Alabama Mitchell Cancer Institute		Mobile	Alabama	36688	United States
Eden Hospital Medical Center

PubMed Identifier	Type	Citation	Retractions
30193295	Derived	Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig GW, Royce ME, Hunt KK. Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent Chemotherapy: The ACOSOG Z1041 (Alliance) Randomized Clinical Trial. JAMA Oncol. 2019 Jan 1;5(1):45-50. doi: 10.1001/jamaoncol.2018.3691.
28453704	Derived	Lesurf R, Griffith OL, Griffith M, Hundal J, Trani L, Watson MA, Aft R, Ellis MJ, Ota D, Suman VJ, Meric-Bernstam F, Leitch AM, Boughey JC, Unzeitig G, Buzdar AU, Hunt KK, Mardis ER. Genomic characterization of HER2-positive breast cancer and response to neoadjuvant trastuzumab and chemotherapy-results from the ACOSOG Z1041 (Alliance) trial. Ann Oncol. 2017 May 1;28(5):1070-1077. doi: 10.1093/annonc/mdx048.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive FEC comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive FEC comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
BG001	Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75	Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
BG002	Total	Total of all reporting groups

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

pCR Within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapy

Pathological complete response (pCR) rates will be based on institutional pathology reports. In the final analysis for publication, rates will be based on blinded central review of these institutional pathology reports. The Chi-squared test will be conducted at the two-sided 0.05 level. A 95% confidence interval will be computed for the difference in pCR rates.

All patients who started study treatment are included in the analysis of the primary endpoint.

Posted

Number

95% Confidence Interval

percentage of participants

Up to 5 years

ID	Title	Description
OG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive Fluorouracil, epirubicin, and cyclophosphamide (FEC) comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
OG001	Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75	Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies

Units	Counts
Participants	OG000138 OG001142

Title

Denominators

Categories

Title	Measurements
	OG00056.5(47.8 to 64.9) OG00154.2(45.7 to 62.6)

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 OG001	The difference in pCR rates between treatment arms for pCR within the Breast, Defined as no Evidence of Invasive Tumor Remaining in the Breast at Surgery Following Completion of Chemotherapy	Chi-squared		.7		difference in percentages between arms	2.3			2-Sided	95	-9.3	13.9					Superiority or Other

Secondary

Combined pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy

pCR Rate in the Breast and Axillary Lymph Nodes Defined as no Evidence of Invasive Tumor Remaining in Either the Breast or Axillary Nodes at Surgery Following Completion of Chemotherapy (among those with Metastasis to movable ipsilateral axillary lymph node(s) (cN1-3) disease).

All patients who had clinical N1-3 disease prior to the start of treatment are included in the analysis of the pCR rate in the breast and axillary lymph nodes.

Posted

Number

95% Confidence Interval

Percentage (95% confidence Interval)

Up to 5 years

ID	Title	Description
OG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive Fluorouracil, epirubicin, and cyclophosphamide (FEC) comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
OG001	Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75

Secondary

Asymptomatic Decreases From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 12

The summary of asymptomatic decrease in LVEF.

All patients who had a MUGA or ECHO performed at week 12 are included in the summary of asymptomatic changed in LVEF at week 12.

Posted

Number

Percentage of participants

Baseline, at 12 week

ID	Title	Description
OG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive Fluorouracil, epirubicin, and cyclophosphamide (FEC) comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
OG001	Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75	Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies

Secondary

Asymptomatic Decreases From Baseline in LVEF at Week 24

The summary of asymptomatic changed in LVEF.

All patients who had a MUGA or ECHO performed at week 24 are included in the summary of asymptomatic changed in LVEF at week 24.

Posted

Number

Percentage of Participants

Baseline, at 24 week

ID	Title	Description
OG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive Fluorouracil, epirubicin, and cyclophosphamide (FEC) comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
OG001	Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75	Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies

Secondary

LVEFs From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans as Reported at 12 Week

All patients who had a MUGA or ECHO performed at week 12 are included in the summary of asymptomatic changed in LVEF at week 12. Difference from pretreatment LVEF (%) at 12 weeks [median change from baseline Inter Quartile Range (IQR)].

Posted

Median

Inter-Quartile Range

percent

At 12 week

ID	Title	Description
OG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive Fluorouracil, epirubicin, and cyclophosphamide (FEC) comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
OG001	Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75	Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies

Secondary

Change in LVEFs (From Regularly Scheduled Multi Gated Acquisition Scan (MUGA)/Echo Scans) From Baseline and at 24 Week

Difference from pretreatment LVEF (%) at 24 weeks [median change from baseline Inter Quartile Range (IQR)].

All patients who had a MUGA or ECHO performed at week 24 are included in the summary of asymptomatic changed in LVEF at week 24.

Posted

Median

Inter-Quartile Range

percent

Baseline, at 24 week

ID	Title	Description
OG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive Fluorouracil, epirubicin, and cyclophosphamide (FEC) comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
OG001	Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75	Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies

Secondary

Breast Conservation

Surgery was categorized as breast conserving surgery ("Partial Mastectomy") or non-conserving surgery ("Total Mastectomy" or "Modified Radical Mastectomy). Reported below is the percentage of patients receiving "Partial Mastectomy". This was calculated by dividing the number of patients receiving "Partial Mastectomy" by the total number of patients undergoing surgery multiplied by 100 (to obtain the percentage).

All patients that underwent breast surgery were included in this analysis.

Posted

Number

percentage of participants

From time surgery to up to 5 years

ID	Title	Description
OG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive Fluorouracil, epirubicin, and cyclophosphamide (FEC) comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
OG001	Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75

Secondary

Disease-free Survival (DFS)

DFS defined as inoperable progressive disease, gross residual disease following definitive surgery, local, regional or distant recurrence, contralateral breast cancer, other second primary cancers, and death prior to recurrence or second primary cancer. DFS of Arm I and Arm II patients will be estimated using the Kaplan-Meier method.

All patients that began protocol therapy are included in this analysis

Posted

Median

95% Confidence Interval

months

From time to registration to time of event, assessed up to 5 years

ID	Title	Description
OG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive Fluorouracil, epirubicin, and cyclophosphamide (FEC) comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
OG001	Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75	Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies

Secondary

Overall Survival (OS)

OS of Arm I and Arm II patients will be estimated using the Kaplan-Meier method.

All patients that began protocol therapy were included in this analysis.

Posted

Median

95% Confidence Interval

months

From time to registration to death, assessed up to 5 years

ID	Title	Description
OG000	FEC-75 Then Paclitaxel/Trastuzumab	Patients receive Fluorouracil, epirubicin, and cyclophosphamide (FEC) comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies
OG001	Paclitaxel/Trastuzumab Then Trastuzumab/FEC-75	Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A	Patients receive FEC comprising fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of FEC, patients receive paclitaxel IV once weekly and trastuzumab (Herceptin) IV once weekly for 12 weeks. Within 6 weeks after completion of paclitaxel and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab IV once every 3 weeks for up to 52 weeks. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies			19	138	136	138
EG001	Arm B	Patients receive paclitaxel IV once weekly and trastuzumab IV once weekly for 12 weeks. Beginning 7 days after the completion of paclitaxel and trastuzumab, patients receive FEC comprising fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients also receive trastuzumab IV once weekly for an additional 12 weeks. Within 6 weeks after completion of FEC and trastuzumab, patients undergo surgery. Beginning 3-4 weeks after surgery, patients receive trastuzumab as in arm I. epirubicin hydrochloride: Given IV, cyclophosphamide: Given IV, paclitaxel: Given IV, trastuzumab: Given IV, therapeutic conventional surgery: Undergo surgery, laboratory biomarker analysis: Correlative studies			26	142	141	142

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Blood disorder	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0014 events3 affected142 at risk
Hemoglobin decreased	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG00012 events8 affected138 at risk EG00114 events11 affected142 at risk
Hemolysis	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Left ventricular failure	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG0016 events5 affected142 at risk
Myocardial ischemia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Extraocular muscle paresis	Eye disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Eyelid function disorder	Eye disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Vision blurred	Eye disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0003 events2 affected138 at risk EG0013 events3 affected142 at risk
Anal pain	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Colonic hemorrhage	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Constipation	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0004 events4 affected138 at risk EG0014 events4 affected142 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG00012 events9 affected138 at risk EG0018 events8 affected142 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0013 events2 affected142 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Ear, nose and throat examination abnormal	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0006 events4 affected138 at risk EG0010 events0 affected142 at risk
Gastritis	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Ileus	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Nausea	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG00011 events10 affected138 at risk EG00110 events8 affected142 at risk
Rectal hemorrhage	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Stomach pain	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Upper gastrointestinal hemorrhage	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Vomiting	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0005 events5 affected138 at risk EG0016 events6 affected142 at risk
Chest pain	General disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Chills	General disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Edema limbs	General disorders	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG0014 events4 affected142 at risk
Fatigue	General disorders	MedDRA 9	Systematic Assessment	EG00023 events13 affected138 at risk EG00123 events17 affected142 at risk
Fever	General disorders	MedDRA 9	Systematic Assessment	EG0007 events6 affected138 at risk EG0014 events4 affected142 at risk
Localized edema	General disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0010 events0 affected142 at risk
Pain	General disorders	MedDRA 9	Systematic Assessment	EG0002 events1 affected138 at risk EG0011 events1 affected142 at risk
Cytokine release syndrome	Immune system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Bladder infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Bronchitis	Infections and infestations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0014 events3 affected142 at risk
Peripheral nerve infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Pharyngitis	Infections and infestations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Pneumonia	Infections and infestations	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0014 events4 affected142 at risk
Skin infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0005 events5 affected138 at risk EG0012 events2 affected142 at risk
Soft tissue infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0002 events1 affected138 at risk EG0010 events0 affected142 at risk
Upper respiratory infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Urinary tract infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Wound infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Dermatitis radiation	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0002 events1 affected138 at risk EG0012 events2 affected142 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Vascular access complication	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Alanine aminotransferase increased	Investigations	MedDRA 9	Systematic Assessment	EG0007 events4 affected138 at risk EG0012 events2 affected142 at risk
Alkaline phosphatase increased	Investigations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 9	Systematic Assessment	EG0004 events2 affected138 at risk EG0013 events3 affected142 at risk
Creatinine increased	Investigations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
INR increased	Investigations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Laboratory test abnormal	Investigations	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0012 events1 affected142 at risk
Leukocyte count decreased	Investigations	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG00112 events8 affected142 at risk
Lymphocyte count decreased	Investigations	MedDRA 9	Systematic Assessment	EG0003 events1 affected138 at risk EG00111 events6 affected142 at risk
Neutrophil count decreased	Investigations	MedDRA 9	Systematic Assessment	EG0007 events6 affected138 at risk EG00120 events13 affected142 at risk
Platelet count decreased	Investigations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0013 events3 affected142 at risk
Serum cholesterol increased	Investigations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Weight gain	Investigations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0013 events3 affected142 at risk
Weight loss	Investigations	MedDRA 9	Systematic Assessment	EG0004 events3 affected138 at risk EG0012 events2 affected142 at risk
Alkalosis	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0004 events3 affected138 at risk EG0016 events6 affected142 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0004 events3 affected138 at risk EG0012 events2 affected142 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0013 events3 affected142 at risk
Hyperkalemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Hypernatremia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Hypocalcemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Hypoglycemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0002 events1 affected138 at risk EG0013 events3 affected142 at risk
Hyponatremia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0004 events2 affected138 at risk EG0010 events0 affected142 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Chest wall pain	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0014 events2 affected142 at risk
Joint pain	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG0013 events3 affected142 at risk
Muscle weakness	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0002 events1 affected138 at risk EG0012 events1 affected142 at risk
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Musculoskeletal disorder	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0014 events1 affected142 at risk
Dizziness	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0013 events3 affected142 at risk
Encephalopathy	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0002 events1 affected138 at risk EG0010 events0 affected142 at risk
Headache	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0007 events6 affected138 at risk EG00110 events9 affected142 at risk
Neurological disorder NOS	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0009 events1 affected138 at risk EG0010 events0 affected142 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events1 affected142 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0006 events5 affected138 at risk EG00110 events8 affected142 at risk
Syncope	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0012 events2 affected142 at risk
Taste alteration	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0004 events1 affected138 at risk EG0012 events1 affected142 at risk
Tremor	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Agitation	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Anxiety	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG0004 events2 affected138 at risk EG0012 events2 affected142 at risk
Confusion	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Depression	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG0004 events2 affected138 at risk EG0018 events7 affected142 at risk
Insomnia	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG0003 events1 affected138 at risk EG0015 events5 affected142 at risk
Breast pain	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Irregular menstruation	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Adult respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Bronchopulmonary hemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG0014 events4 affected142 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0007 events7 affected138 at risk EG0017 events7 affected142 at risk
Hemorrhage nasal	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0011 events1 affected142 at risk
Voice alteration	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0003 events1 affected138 at risk EG0011 events1 affected142 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00013 events9 affected138 at risk EG00114 events11 affected142 at risk
Hand-and-foot syndrome	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0004 events4 affected138 at risk EG0011 events1 affected142 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Rash desquamating	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Skin ulceration	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Sweating	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Hematoma	Vascular disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Hemorrhage	Vascular disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Hot flashes	Vascular disorders	MedDRA 9	Systematic Assessment	EG0003 events2 affected138 at risk EG0012 events2 affected142 at risk
Hypertension	Vascular disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0011 events1 affected142 at risk
Hypotension	Vascular disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0012 events1 affected142 at risk
Thrombosis	Vascular disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0014 events3 affected142 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Blood disorder	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG0006 events3 affected138 at risk EG0017 events5 affected142 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG0003 events2 affected138 at risk EG0013 events3 affected142 at risk
Hemoglobin decreased	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG000279 events53 affected138 at risk EG001269 events50 affected142 at risk
Hemolysis	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0018 events2 affected142 at risk
Lymph node pain	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Lymphatic disorder	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0015 events2 affected142 at risk
Thrombotic microangiopathy	Blood and lymphatic system disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0018 events5 affected142 at risk
Arrhythmia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0004 events3 affected138 at risk EG0011 events1 affected142 at risk
Cardiac disorder	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Left ventricular failure	Cardiac disorders	MedDRA 9	Systematic Assessment	EG00014 events9 affected138 at risk EG00125 events18 affected142 at risk
Myocardial ischemia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Palpitations	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0007 events5 affected138 at risk EG0014 events4 affected142 at risk
Pericardial effusion	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0014 events3 affected142 at risk
Premature ventricular contractions	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Sinus arrhythmia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG00012 events9 affected138 at risk EG00114 events8 affected142 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG00114 events2 affected142 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0019 events1 affected142 at risk
Ear disorder	Ear and labyrinth disorders	MedDRA 9	Systematic Assessment	EG0003 events1 affected138 at risk EG0012 events2 affected142 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
External ear inflammation	Ear and labyrinth disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
External ear pain	Ear and labyrinth disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Hearing loss	Ear and labyrinth disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events1 affected142 at risk
Middle ear inflammation	Ear and labyrinth disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Hypothyroidism	Endocrine disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Conjunctival disorder	Eye disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Dry eye syndrome	Eye disorders	MedDRA 9	Systematic Assessment	EG0003 events2 affected138 at risk EG0015 events3 affected142 at risk
Extraocular muscle paresis	Eye disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0010 events0 affected142 at risk
Eye disorder	Eye disorders	MedDRA 9	Systematic Assessment	EG0005 events1 affected138 at risk EG00117 events9 affected142 at risk
Eye pain	Eye disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Eyelid function disorder	Eye disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Vision blurred	Eye disorders	MedDRA 9	Systematic Assessment	EG00014 events11 affected138 at risk EG00137 events16 affected142 at risk
Watering eyes	Eye disorders	MedDRA 9	Systematic Assessment	EG0004 events2 affected138 at risk EG0019 events3 affected142 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0019 events4 affected142 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG00012 events9 affected138 at risk EG00124 events16 affected142 at risk
Anal hemorrhage	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Anal mucositis	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Colitis	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Constipation	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG000142 events57 affected138 at risk EG001113 events51 affected142 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG000172 events72 affected138 at risk EG001210 events79 affected142 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0013 events3 affected142 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG00048 events16 affected138 at risk EG00152 events24 affected142 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0005 events4 affected138 at risk EG0019 events6 affected142 at risk
Ear, nose and throat examination abnormal	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG00086 events46 affected138 at risk EG00178 events41 affected142 at risk
Endoscopy large bowel abnormal	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Enteritis	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Esophageal mucositis	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0004 events2 affected138 at risk EG0011 events1 affected142 at risk
Esophagitis	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0002 events1 affected138 at risk EG0010 events0 affected142 at risk
Flatulence	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Gastric mucositis	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Gastritis	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG00110 events8 affected142 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0004 events3 affected138 at risk EG00110 events9 affected142 at risk
Gingival pain	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0013 events3 affected142 at risk
Hemorrhoids	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0006 events3 affected138 at risk EG0019 events7 affected142 at risk
Ileus	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0010 events0 affected142 at risk
Mucositis oral	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG00031 events21 affected138 at risk EG00131 events17 affected142 at risk
Nausea	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG000325 events101 affected138 at risk EG001315 events108 affected142 at risk
Oral hemorrhage	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Oral pain	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0011 events1 affected142 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Proctitis	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Rectal hemorrhage	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0011 events1 affected142 at risk
Salivary gland disorder	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Stomach pain	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0015 events5 affected142 at risk
Tooth disorder	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Toothache	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0014 events4 affected142 at risk
Vomiting	Gastrointestinal disorders	MedDRA 9	Systematic Assessment	EG00098 events54 affected138 at risk EG00189 events46 affected142 at risk
Chest pain	General disorders	MedDRA 9	Systematic Assessment	EG0005 events5 affected138 at risk EG00112 events9 affected142 at risk
Chills	General disorders	MedDRA 9	Systematic Assessment	EG00014 events8 affected138 at risk EG00112 events7 affected142 at risk
Edema limbs	General disorders	MedDRA 9	Systematic Assessment	EG00047 events28 affected138 at risk EG00185 events29 affected142 at risk
Fatigue	General disorders	MedDRA 9	Systematic Assessment	EG000768 events124 affected138 at risk EG001711 events126 affected142 at risk
Fever	General disorders	MedDRA 9	Systematic Assessment	EG00011 events10 affected138 at risk EG00128 events21 affected142 at risk
Flu-like symptoms	General disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0012 events2 affected142 at risk
General symptom	General disorders	MedDRA 9	Systematic Assessment	EG0004 events3 affected138 at risk EG0014 events3 affected142 at risk
Ill-defined disorder	General disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Localized edema	General disorders	MedDRA 9	Systematic Assessment	EG0009 events8 affected138 at risk EG0017 events4 affected142 at risk
Pain	General disorders	MedDRA 9	Systematic Assessment	EG00044 events21 affected138 at risk EG00146 events28 affected142 at risk
Visceral edema	General disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Cytokine release syndrome	Immune system disorders	MedDRA 9	Systematic Assessment	EG0005 events4 affected138 at risk EG0016 events4 affected142 at risk
Hypersensitivity	Immune system disorders	MedDRA 9	Systematic Assessment	EG0009 events2 affected138 at risk EG0016 events4 affected142 at risk
Immune system disorder	Immune system disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0018 events3 affected142 at risk
Anal infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Bladder infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG0013 events3 affected142 at risk
Bronchitis	Infections and infestations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Catheter related infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events1 affected142 at risk
Gingival infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG00011 events9 affected138 at risk EG00116 events12 affected142 at risk
Infectious colitis	Infections and infestations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Laryngitis	Infections and infestations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Nail infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Otitis externa	Infections and infestations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Peripheral nerve infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG0010 events0 affected142 at risk
Pharyngitis	Infections and infestations	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG0010 events0 affected142 at risk
Pneumonia	Infections and infestations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0015 events4 affected142 at risk
Rhinitis infective	Infections and infestations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Sepsis	Infections and infestations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Sinusitis	Infections and infestations	MedDRA 9	Systematic Assessment	EG0009 events6 affected138 at risk EG00111 events10 affected142 at risk
Skin infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG00010 events7 affected138 at risk EG0014 events3 affected142 at risk
Tooth infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Upper respiratory infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG00018 events14 affected138 at risk EG00114 events13 affected142 at risk
Urinary tract infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0005 events4 affected138 at risk EG0017 events7 affected142 at risk
Vaginal infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0015 events3 affected142 at risk
Wound infection	Infections and infestations	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Aortic injury	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Bruising	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0003 events2 affected138 at risk EG00110 events3 affected142 at risk
Dermatitis radiation	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0009 events8 affected138 at risk EG0019 events9 affected142 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0006 events1 affected138 at risk EG0011 events1 affected142 at risk
Intraoperative breast injury	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Pharyngeal anastomotic leak	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Radiation recall reaction (dermatologic)	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0004 events3 affected138 at risk EG0014 events4 affected142 at risk
Seroma	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0016 events6 affected142 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0012 events1 affected142 at risk
Vascular access complication	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0004 events3 affected138 at risk EG0011 events1 affected142 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 9	Systematic Assessment	EG0004 events4 affected138 at risk EG0014 events4 affected142 at risk
Alanine aminotransferase increased	Investigations	MedDRA 9	Systematic Assessment	EG000104 events27 affected138 at risk EG00187 events35 affected142 at risk
Alkaline phosphatase increased	Investigations	MedDRA 9	Systematic Assessment	EG00044 events14 affected138 at risk EG00141 events12 affected142 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 9	Systematic Assessment	EG00077 events26 affected138 at risk EG00178 events28 affected142 at risk
Bilirubin increased	Investigations	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0014 events3 affected142 at risk
Creatinine increased	Investigations	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0015 events3 affected142 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 9	Systematic Assessment	EG0005 events2 affected138 at risk EG00110 events2 affected142 at risk
Laboratory test abnormal	Investigations	MedDRA 9	Systematic Assessment	EG0008 events3 affected138 at risk EG00122 events7 affected142 at risk
Leukocyte count decreased	Investigations	MedDRA 9	Systematic Assessment	EG000129 events38 affected138 at risk EG001149 events35 affected142 at risk
Lymphocyte count decreased	Investigations	MedDRA 9	Systematic Assessment	EG00099 events22 affected138 at risk EG001103 events21 affected142 at risk
Neutrophil count decreased	Investigations	MedDRA 9	Systematic Assessment	EG000147 events70 affected138 at risk EG001202 events75 affected142 at risk
Platelet count decreased	Investigations	MedDRA 9	Systematic Assessment	EG0006 events6 affected138 at risk EG00130 events13 affected142 at risk
Weight gain	Investigations	MedDRA 9	Systematic Assessment	EG00020 events10 affected138 at risk EG00139 events14 affected142 at risk
Weight loss	Investigations	MedDRA 9	Systematic Assessment	EG00017 events9 affected138 at risk EG00121 events8 affected142 at risk
Alkalosis	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG00071 events27 affected138 at risk EG00178 events27 affected142 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0005 events4 affected138 at risk EG0016 events6 affected142 at risk
Hypercalcemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG00014 events3 affected138 at risk EG0014 events4 affected142 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG00052 events16 affected138 at risk EG00189 events22 affected142 at risk
Hyperkalemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0015 events5 affected142 at risk
Hypertriglyceridemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0013 events1 affected142 at risk
Hypocalcemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG00112 events9 affected142 at risk
Hypoglycemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events1 affected142 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG00033 events14 affected138 at risk EG00132 events15 affected142 at risk
Hypomagnesemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0016 events2 affected142 at risk
Hyponatremia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0009 events7 affected138 at risk EG00114 events7 affected142 at risk
Hypophosphatemia	Metabolism and nutrition disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG00111 events6 affected142 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG00021 events13 affected138 at risk EG00130 events21 affected142 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG00023 events11 affected138 at risk EG00122 events16 affected142 at risk
Chest wall pain	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG00017 events15 affected138 at risk EG00119 events14 affected142 at risk
Fibrosis	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0005 events3 affected138 at risk EG0011 events1 affected142 at risk
Joint disorder	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0005 events3 affected138 at risk EG0013 events3 affected142 at risk
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Joint pain	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG00069 events38 affected138 at risk EG001103 events45 affected142 at risk
Muscle weakness	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0006 events5 affected138 at risk EG0018 events8 affected142 at risk
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Muscle weakness upper limb	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Musculoskeletal deformity	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Musculoskeletal disorder	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0004 events2 affected138 at risk EG0014 events4 affected142 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG000107 events39 affected138 at risk EG001132 events48 affected142 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0008 events8 affected138 at risk EG0015 events5 affected142 at risk
Neck soft tissue necrosis	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0013 events1 affected142 at risk
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG0002 events1 affected138 at risk EG0011 events1 affected142 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 9	Systematic Assessment	EG00036 events23 affected138 at risk EG00134 events18 affected142 at risk
Tumor pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Ataxia	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0003 events3 affected138 at risk EG0012 events1 affected142 at risk
Cognitive disturbance	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0011 events1 affected142 at risk
Dizziness	Nervous system disorders	MedDRA 9	Systematic Assessment	EG00034 events23 affected138 at risk EG00135 events23 affected142 at risk
Facial nerve disorder	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events1 affected142 at risk
Headache	Nervous system disorders	MedDRA 9	Systematic Assessment	EG00072 events40 affected138 at risk EG00179 events38 affected142 at risk
Hypoglossal nerve disorder	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0013 events1 affected142 at risk
Intracranial hemorrhage	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Leukoencephalopathy	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0013 events1 affected142 at risk
Memory impairment	Nervous system disorders	MedDRA 9	Systematic Assessment	EG00013 events7 affected138 at risk EG0015 events5 affected142 at risk
Mini mental status examination abnormal	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Neuralgia	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0013 events2 affected142 at risk
Neurological disorder NOS	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0004 events2 affected138 at risk EG00110 events6 affected142 at risk
Olfactory nerve disorder	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 9	Systematic Assessment	EG00022 events11 affected138 at risk EG00131 events15 affected142 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 9	Systematic Assessment	EG000352 events92 affected138 at risk EG001436 events104 affected142 at risk
Seizure	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Sinus pain	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Syncope	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0003 events1 affected138 at risk EG0011 events1 affected142 at risk
Taste alteration	Nervous system disorders	MedDRA 9	Systematic Assessment	EG00037 events10 affected138 at risk EG00162 events20 affected142 at risk
Tremor	Nervous system disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Agitation	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG0006 events5 affected138 at risk EG0012 events2 affected142 at risk
Anxiety	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG00062 events15 affected138 at risk EG00160 events23 affected142 at risk
Confusion	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0011 events1 affected142 at risk
Depression	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG00042 events15 affected138 at risk EG00150 events19 affected142 at risk
Insomnia	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG00073 events30 affected138 at risk EG00176 events43 affected142 at risk
Libido decreased	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0016 events1 affected142 at risk
Psychosis	Psychiatric disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Bladder pain	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Cystitis	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0010 events0 affected142 at risk
Hemoglobinuria	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0010 events0 affected142 at risk
Hemorrhage urinary tract	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Kidney pain	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0010 events0 affected142 at risk
Proteinuria	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0010 events0 affected142 at risk
Urinary frequency	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0014 events4 affected142 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0016 events2 affected142 at risk
Urinary retention	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0012 events1 affected142 at risk
Urine discoloration	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Urogenital disorder	Renal and urinary disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0014 events3 affected142 at risk
Breast pain	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG00038 events28 affected138 at risk EG00146 events28 affected142 at risk
Irregular menstruation	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0018 events6 affected142 at risk
Lactation disorder	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Ovulation pain	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG00110 events5 affected142 at risk
Reproductive tract disorder	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0003 events1 affected138 at risk EG0010 events0 affected142 at risk
Uterine hemorrhage	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Vaginal discharge	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0015 events4 affected142 at risk
Vaginal dryness	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0007 events4 affected138 at risk EG0017 events4 affected142 at risk
Vaginal hemorrhage	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0013 events3 affected142 at risk
Vaginal inflammation	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Vaginal mucositis	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Vaginal pain	Reproductive system and breast disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0009 events9 affected138 at risk EG00123 events16 affected142 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0012 events2 affected142 at risk
Bronchial hemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Bronchopulmonary hemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0013 events2 affected142 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0006 events4 affected138 at risk EG0010 events0 affected142 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG00054 events27 affected138 at risk EG00140 events21 affected142 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG00040 events24 affected138 at risk EG00150 events25 affected142 at risk
Hemorrhage nasal	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG00013 events8 affected138 at risk EG00121 events13 affected142 at risk
Hiccough	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Laryngeal edema	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Laryngeal mucositis	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0004 events1 affected138 at risk EG0011 events1 affected142 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0009 events7 affected138 at risk EG00124 events13 affected142 at risk
Pharyngeal mucositis	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0008 events5 affected138 at risk EG00111 events9 affected142 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0013 events3 affected142 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0000 events0 affected138 at risk EG0011 events1 affected142 at risk
Pulmonary hemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG00023 events11 affected138 at risk EG00111 events10 affected142 at risk
Voice alteration	Respiratory, thoracic and mediastinal disorders	MedDRA 9	Systematic Assessment	EG0006 events3 affected138 at risk EG0013 events2 affected142 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG000588 events93 affected138 at risk EG001579 events98 affected142 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0012 events2 affected142 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00011 events7 affected138 at risk EG0016 events4 affected142 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00011 events8 affected138 at risk EG0016 events5 affected142 at risk
Hand-and-foot syndrome	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00026 events17 affected138 at risk EG00128 events15 affected142 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00071 events33 affected138 at risk EG00193 events42 affected142 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0007 events4 affected138 at risk EG0017 events6 affected142 at risk
Photosensitivity	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0010 events0 affected142 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00016 events11 affected138 at risk EG00114 events14 affected142 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00021 events15 affected138 at risk EG00129 events16 affected142 at risk
Rash desquamating	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00042 events24 affected138 at risk EG00159 events40 affected142 at risk
Scalp pain	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0016 events1 affected142 at risk
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00022 events12 affected138 at risk EG00115 events9 affected142 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00024 events9 affected138 at risk EG00160 events25 affected142 at risk
Skin hypopigmentation	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0015 events2 affected142 at risk
Skin induration	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Skin ulceration	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0012 events2 affected142 at risk
Sweating	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG00010 events7 affected138 at risk EG00113 events7 affected142 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Flushing	Vascular disorders	MedDRA 9	Systematic Assessment	EG0005 events2 affected138 at risk EG00110 events8 affected142 at risk
Hemorrhage	Vascular disorders	MedDRA 9	Systematic Assessment	EG0002 events2 affected138 at risk EG0016 events4 affected142 at risk
Hot flashes	Vascular disorders	MedDRA 9	Systematic Assessment	EG000101 events40 affected138 at risk EG001101 events45 affected142 at risk
Hypertension	Vascular disorders	MedDRA 9	Systematic Assessment	EG000100 events25 affected138 at risk EG00183 events24 affected142 at risk
Hypotension	Vascular disorders	MedDRA 9	Systematic Assessment	EG0006 events3 affected138 at risk EG00110 events6 affected142 at risk
Peripheral ischemia	Vascular disorders	MedDRA 9	Systematic Assessment	EG0001 events1 affected138 at risk EG0011 events1 affected142 at risk
Phlebitis	Vascular disorders	MedDRA 9	Systematic Assessment	EG0003 events2 affected138 at risk EG0010 events0 affected142 at risk
Thrombosis	Vascular disorders	MedDRA 9	Systematic Assessment	EG0005 events4 affected138 at risk EG0015 events5 affected142 at risk

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D003520	Cyclophosphamide
D015251	Epirubicin
D017239	Paclitaxel
D013660	Taxes
D000068878	Trastuzumab
C000598430	PF-05280014

ID	Term
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D004317	Doxorubicin
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D004224	Diterpenes
D013729	Terpenes
D004467	Economics
D004472	Health Care Economics and Organizations
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins