Trial Outcomes & Findings for Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment (NCT NCT00121992)

NCT ID: NCT00121992

Last Updated: 2023-04-04

Results Overview

DFS is calculated from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1060 participants

Primary outcome timeframe

10 years

Results posted on

2023-04-04

Participant Flow

For the different subsets ("Hormone-receptor Positive and HER2 PositiveStatus Subjects", "Hormonal Receptor Positive and HER2 Negative Subjects", etc.), were assessed by central determination, and no all patients had tumor sample available.

Participant milestones

Participant milestones
Measure	Arm A: FAC FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
Overall Study STARTED	521	539
Overall Study Hormone-receptor Positive and HER2 Positive Status Subjects	28	30
Overall Study Hormone-receptor Negative and HER2 Positive Status Subjects	24	22
Overall Study Hormone-receptor Positive and HER2 Negative Status Subjects	209	220
Overall Study Hormone-receptor Negative and HER2 Negative Status Subjects	92	103
Overall Study COMPLETED	519	528
Overall Study NOT COMPLETED	2	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: FAC FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
Overall Study Treatment not received	2	11

Baseline Characteristics

Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: FAC n=521 Participants FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC n=539 Participants TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide	Total n=1060 Participants Total of all reporting groups
Age, Continuous	49 years n=5 Participants	50 years n=7 Participants	49 years n=5 Participants
Sex: Female, Male Female	521 Participants n=5 Participants	539 Participants n=7 Participants	1060 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Spain	475 participants n=5 Participants	487 participants n=7 Participants	962 participants n=5 Participants
Region of Enrollment Germany	26 participants n=5 Participants	30 participants n=7 Participants	56 participants n=5 Participants
Region of Enrollment Poland	20 participants n=5 Participants	22 participants n=7 Participants	42 participants n=5 Participants
Tumor size ≤2 cm	249 Participants n=5 Participants	285 Participants n=7 Participants	534 Participants n=5 Participants
Tumor size >2 to 5 cm	258 Participants n=5 Participants	241 Participants n=7 Participants	499 Participants n=5 Participants
Tumor size >5 cm	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Tumor size Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Tumor grade Grade 1	34 Participants n=5 Participants	38 Participants n=7 Participants	72 Participants n=5 Participants
Tumor grade Grade 2	230 Participants n=5 Participants	216 Participants n=7 Participants	446 Participants n=5 Participants
Tumor grade Grade 3	231 Participants n=5 Participants	259 Participants n=7 Participants	490 Participants n=5 Participants
Tumor grade Unknown	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Menopausal status Premenopausal	272 Participants n=5 Participants	285 Participants n=7 Participants	557 Participants n=5 Participants
Menopausal status Postmenopausal	249 Participants n=5 Participants	254 Participants n=7 Participants	503 Participants n=5 Participants
Hormone-receptor status Positive	349 Participants n=5 Participants	344 Participants n=7 Participants	693 Participants n=5 Participants
Hormone-receptor status Negative	170 Participants n=5 Participants	192 Participants n=7 Participants	362 Participants n=5 Participants
Hormone-receptor status Unknown	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Surgery Breast-conserving surgery: With radiation	247 Participants n=5 Participants	287 Participants n=7 Participants	534 Participants n=5 Participants
Surgery Breast-conserving surgery: Without radiation	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Surgery Mastectomy: With radiation	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Surgery Mastectomy: Without radiation	230 Participants n=5 Participants	206 Participants n=7 Participants	436 Participants n=5 Participants

PRIMARY outcome

Timeframe: 10 years

DFS is calculated from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death.

Outcome measures

Outcome measures
Measure	Arm A: FAC n=521 Participants FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC n=539 Participants TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
Disease-free Survival (DFS) Events	127 events	112 events

SECONDARY outcome

Timeframe: 10 years

OS was determined from the date of randomization until the date of death for any reason. OS is calculated from the date of randomization up to the first date of death by any cause.

Outcome measures

Outcome measures
Measure	Arm A: FAC n=521 Participants FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC n=539 Participants TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
Overall Survival (OS)	57 Participants with mortality event	53 Participants with mortality event

SECONDARY outcome

Timeframe: Through study treatment, and average of 4 months

Population: The safety analysis was conducted on all patients who started at least one infusion of the study treatment (Arm A 519, and Arm B 532).

Safety was assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 1.0.

Outcome measures

Outcome measures
Measure	Arm A: FAC n=519 Participants FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC n=532 Participants TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
The Number of Participants Who Experienced Adverse Events (AE) Number patients with One AE	519 participants	532 participants
The Number of Participants Who Experienced Adverse Events (AE) One G3-4 or severe treatment-emergent AE	88 participants	151 participants
The Number of Participants Who Experienced Adverse Events (AE) One serious treatment-emergent AE	22 participants	119 participants
The Number of Participants Who Experienced Adverse Events (AE) One serious G3-4 treatment-emergent AE	10 participants	55 participants
The Number of Participants Who Experienced Adverse Events (AE) Number of patients discontinued due to AE	4 participants	25 participants
The Number of Participants Who Experienced Adverse Events (AE) Number patients death due to AE	0 participants	1 participants

SECONDARY outcome

Timeframe: 120 weeks

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was used. Questionnaires were self-administered to patients during the 14 days prior to randomisation baseline, at six prospective time points corresponding to chemotherapy cycles, with the time window related to each chemotherapy cycle defined as the period between the day following the first chemotherapy dose of the corresponding cycle and the day of the first dose of the following cycle, and then at 44, 68 and 120 weeks of the study. The Global Health Status Scale has been used, which is calculated with questions 29 and 30 from the EORTC QLQ-C30. From this scale, the best score is the highest score observed during study (of all the questionnaires completed by patient). In this scale, scores range from 0 to 100 and a high score represents a high level of functioning or HRQoL.

Outcome measures

Outcome measures
Measure	Arm A: FAC n=519 Participants FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC n=532 Participants TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
Best Score During Study for Global Health Status Scale	79.30 score on a scale Standard Deviation 17.64	77.78 score on a scale Standard Deviation 18.87

SECONDARY outcome

Timeframe: 10 year

Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first.

Outcome measures

Outcome measures
Measure	Arm A: FAC n=28 Participants FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC n=30 Participants TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
Number of Disease Free Survival Events in Hormone-receptor Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Positive Status Subgroup	6 events	6 events

SECONDARY outcome

Timeframe: 10 year

Outcome measures

Outcome measures
Measure	Arm A: FAC n=209 Participants FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC n=220 Participants TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
Disease Free Survival in Hormonal Receptor Positive and HER2 Negative Subgroup	50 events	37 events

SECONDARY outcome

Timeframe: 10 year

Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally.

Outcome measures

Outcome measures
Measure	Arm A: FAC n=24 Participants FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC n=22 Participants TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
Disease Free Survival in Hormonal Receptor Negative and HER2 Positive Subgroup	6 events	5 events

SECONDARY outcome

Timeframe: 10 year

Outcome measures

Outcome measures
Measure	Arm A: FAC n=92 Participants FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC n=103 Participants TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
Disease Free Survival in Hormonal Receptor Negative and HER2 Negative Subgroup	29 events	28 events

Adverse Events

Arm A: FAC

Serious events: 21 serious events

Other events: 519 other events

Deaths: 57 deaths

Arm B: TAC

Serious events: 119 serious events

Other events: 532 other events

Deaths: 53 deaths

Serious adverse events

Other adverse events

Additional Information

Scientific Director / Medical Lead / Project Manager

Spanish Breast Cancer Research Group

Phone: +34916592870

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm A: FAC n=519 participants at risk FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv 5-fluorouracil Doxorubicin Cyclophosphamide	Arm B: TAC n=532 participants at risk TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv Docetaxel Doxorubicin Cyclophosphamide
Gastrointestinal disorders Abdominal pain	0.19% 1/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Blood and lymphatic system disorders Anaemia	0.19% 1/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Gastrointestinal disorders Anal fissure	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Cardiac disorders Arrhythmia	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
General disorders Asthenia	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Blood and lymphatic system disorders Blood bilirubin	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Reproductive system and breast disorders Breast cyst	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Reproductive system and breast disorders Breast infection	0.19% 1/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.00% 0/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Reproductive system and breast disorders Breast haematoma	0.19% 1/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.00% 0/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Cardiac disorders Carotid artery thrombosis	0.19% 1/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.00% 0/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Infections and infestations Cellulitis	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Respiratory, thoracic and mediastinal disorders Bronchopneumonia	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Gastrointestinal disorders Constipation	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Eye disorders Conjunctivitis	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Vascular disorders Deep vein thrombosis	0.19% 1/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.00% 0/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Infections and infestations Device related infection	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Gastrointestinal disorders Diarrhoea	0.19% 1/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	1.1% 6/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease progression	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Skin and subcutaneous tissue disorders Erysipelas	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Ear and labyrinth disorders Ear infection	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Gastrointestinal disorders Dyspepsia	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Investigations Febrile neutropenia	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.56% 3/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
General disorders Fever in absence of infection	2.3% 12/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	12.8% 68/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
General disorders General physical health deterioration	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Nervous system disorders Hypersensitivity	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Infections and infestations Localised infection	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Blood and lymphatic system disorders Leukopenia	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Gastrointestinal disorders Nausea	0.19% 1/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.75% 4/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Reproductive system and breast disorders Menorrhagia	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Blood and lymphatic system disorders Neutropenia	0.19% 1/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.94% 5/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Vascular disorders Oedema peripheral	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
General disorders Pyrexia	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.38% 2/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Metabolism and nutrition disorders Pancreatitis	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Infections and infestations Postoperative wound infection	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory tract infection	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Infections and infestations Skin infection	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.38% 2/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Vascular disorders Thrombosis	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Respiratory, thoracic and mediastinal disorders Tonsillitis	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.
Infections and infestations Wound infection	0.00% 0/519 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.	0.19% 1/532 • Deaths were assessed for up to 10 years. Adverse Events were assessed for an average of 4 months The safety analysis were conducted on all patients who started at least one infusion of the study treatment.