Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Herceptin® (Trastuzumab) in Combination With Arimidex® (Anastrozole) an Aromatase Inhibitor Compared to Arimidex® Alone in Patients With Metastatic Breast Cancer (NCT NCT00022672)

Last Updated: 2013-06-13

Results Overview

PFS was assessed by the investigator based on World Health Organization (WHO) criteria using radiographic tumor evaluations. Disease progression was defined as the appearance of any new lesion not previously identified or an estimated increase of 25% or more in existent bidimensionally or unidimensionally measurable lesions or progression of an existing non-measurable lesion. For bidimensionally measurable malignant lesions with an area of at least 2.0 centimeters squared (cm\^2) an increase of 1.0 cm\^2 was required and for unidimensionally measurable lesions of 1.0 cm or less an increase of 0.5 cm was required. PFS was defined as the number of days between date of randomization and date of documented disease progression or date of death. Kaplan Meier estimates of PFS are presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

208 participants

Primary outcome timeframe

24 Months, End of Study (Up to 5 years)

Results posted on

2013-06-13

Participant Flow

208 participants were randomized. 1 participant did not receive study drug. After the completion of the 24 month Main Phase or disease progression, participants in the anastrozole-alone treatment arm entered the Extension Phase where they received trastuzumab + anastrozole.

Participant milestones

Participant milestones
Measure	Trastuzumab + Anastrozole Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Main Phase: 24 Months STARTED	103	104
Main Phase: 24 Months Safety Set: Received Study Drug	103	104
Main Phase: 24 Months COMPLETED	16	4
Main Phase: 24 Months NOT COMPLETED	87	100
Extension Phase STARTED	14	58
Extension Phase Safety Set: Received Study Drug	14	58
Extension Phase COMPLETED	11	7
Extension Phase NOT COMPLETED	3	51

Reasons for withdrawal

Reasons for withdrawal
Measure	Trastuzumab + Anastrozole Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Main Phase: 24 Months Adverse Event	6	0
Main Phase: 24 Months Death	0	3
Main Phase: 24 Months Insufficient Therapeutic Response	75	91
Main Phase: 24 Months Violation of Selection Criteria at Entry	0	1
Main Phase: 24 Months Other Protocol Violation	1	0
Main Phase: 24 Months Refused Treatment	3	4
Main Phase: 24 Months Failure to Return	1	1
Main Phase: 24 Months Other	1	0
Extension Phase Adverse Event	1	3
Extension Phase Death	0	1
Extension Phase Insufficient Therapeutic Response	1	44
Extension Phase Refused Treatment	0	2
Extension Phase Other	1	1

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Herceptin® (Trastuzumab) in Combination With Arimidex® (Anastrozole) an Aromatase Inhibitor Compared to Arimidex® Alone in Patients With Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trastuzumab + Anastrozole n=103 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.	Total n=207 Participants Total of all reporting groups
Age Continuous	57.4 years STANDARD_DEVIATION 10.6 • n=5 Participants	55.5 years STANDARD_DEVIATION 10.7 • n=7 Participants	56.5 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	103 Participants n=5 Participants	104 Participants n=7 Participants	207 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 Months, End of Study (Up to 5 years)

Population: Full analysis population included all randomized participants who received study drug.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=103 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Progression Free Survival (PFS) 24 Months	4.8 Months Interval 3.7 to 7.0	2.4 Months Interval 2.0 to 4.6
Progression Free Survival (PFS) End of Study	5.8 Months Interval 4.6 to 8.3	2.9 Months Interval 2.1 to 4.5

SECONDARY outcome

Timeframe: 24 Months, End of Study (Up to 5 years)

Clinical Benefit was defined as stable disease for ≥ six months or complete response or partial response.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=103 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Percentage of Participants With Clinical Benefit 24 Months	42.7 Percentage of participants	27.9 Percentage of participants
Percentage of Participants With Clinical Benefit End of Study	45.6 Percentage of participants	30.8 Percentage of participants

SECONDARY outcome

Timeframe: 24 Months

Population: Participants from the Full Analysis population (all randomized participants who received study drug) evaluable for response.

Duration of response was defined as the number of days from the day complete response or partial response was first noted to the day of progression of disease, death or last follow-up.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=74 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=73 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Duration of Response at 24 Months	9.5 Months Interval 3.8 to 50.6	10.0 Months Interval 5.3 to 33.1

SECONDARY outcome

Timeframe: 24 Months

Population: Participants from the Full Analysis population (all randomized participants who received study drug) evaluable for response.

Time to response was defined as the number of days from the day of randomization to the day complete response or partial response was first noted.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=74 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=73 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Time to Response at 24 Months	2.0 Months Interval 1.4 to 12.1	2.0 Months Interval 1.7 to 4.1

SECONDARY outcome

Timeframe: 24 Months

Overall Survival is defined as the number of days from randomization to death.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=103 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Overall Survival at 24 Months	28.5 Months Interval 22.8 to 42.4	23.9 Months Interval 18.2 to 37.4

SECONDARY outcome

Timeframe: 24 Months

Population: Full Analysis Population included all randomized participants who received study drug.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=103 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Percentage of Participants With Two-Year Survival	52.4 Percentage of participants	45.2 Percentage of participants

SECONDARY outcome

Timeframe: 24 Months

Population: Participants from the Full Analysis Population (all randomized participants who received study drug) evaluable for response.

Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Overall Response was defined as either complete response or partial response.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=74 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=73 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Percentage of Participants With Overall Tumor Response at 24 Months	20.3 Percentage of participants	6.8 Percentage of participants

SECONDARY outcome

Timeframe: 24 Months

Population: Participants from the Full Analysis Population (all randomized participants who received study drug) evaluable for response.

Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Best Response was defined as the best response a patient achieves in the study.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=74 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=73 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Percentage of Participants With Best Tumor Response at 24 Months Response not assessed	1.4 Percentage of participants	5.5 Percentage of participants
Percentage of Participants With Best Tumor Response at 24 Months Complete Response	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Best Tumor Response at 24 Months Partial Response	20.3 Percentage of participants	6.8 Percentage of participants
Percentage of Participants With Best Tumor Response at 24 Months Stable Disease	37.8 Percentage of participants	38.4 Percentage of participants
Percentage of Participants With Best Tumor Response at 24 Months Progressive Disease	40.5 Percentage of participants	49.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Final Visit (Up to 24 Months)

Population: Participants from the Full Analysis Population (includes all randomized participants who received study drug) with data available for analyses.

Participants rated their performance status using the ECOG Questionnaire on the following scale: 0=Fully active, perform all pre-disease activities without restriction; 1=Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature; 2=Ambulatory, capable of self-care, unable to carry out any work activities, up and about more than \>50% of waking hours; 3=Capable of limited self-care, confined to bed or chair \>50% of waking hours; 4=Completely disabled, not capable of any self-care, totally confined to bed or chair; 5=Dead. The percentage of participants in the following categories: Improved: Score decrease from baseline. Unchanged: Score the same as baseline. Worse: Score increase from baseline.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=68 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=73 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Final Visit Compared to Baseline Worse	22.1 Percentage of participants	31.5 Percentage of participants
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Final Visit Compared to Baseline Improved	10.3 Percentage of participants	4.1 Percentage of participants
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Final Visit Compared to Baseline No Change	67.6 Percentage of participants	64.4 Percentage of participants

SECONDARY outcome

Timeframe: End of Study (Up to 5 years)

Population: Participants from the Full Analysis population (all randomized participants who received study drug) evaluable for response.

Duration of response was defined as the number of days from the day complete response or partial response was first noted to the day of progression of disease, death or last follow-up.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=103 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Duration of Response at End of Study	12.3 Months Interval 3.0 to 59.1	8.2 Months Interval 2.6 to 60.5

SECONDARY outcome

Timeframe: End of Study (Up to 5 years)

Population: Participants from the Full Analysis population (all randomized participants who received study drug) evaluable for response.

Time to response was defined as the number of days from the day of randomization to the day complete response or partial response was first noted.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=103 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Time to Response at End of Study	2.4 Months Interval 1.7 to 12.1	2.1 Months Interval 1.3 to 5.1

SECONDARY outcome

Timeframe: End of Study (Up to 5 years)

Population: Participants from the Full Analysis Population (all randomized participants who received study drug) evaluable for response.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=103 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Percentage of Participants With Overall Tumor Response at End of Study	22.3 Percentage of participants	8.7 Percentage of participants

SECONDARY outcome

Timeframe: End of Study (Up to 5 years)

Population: Full Analysis Population includes all randomized participants who received study drug.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=103 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Percentage of Participants With Best Tumor Response at End of Study Complete Response	1.0 Percentage of participants	3.8 Percentage of participants
Percentage of Participants With Best Tumor Response at End of Study Response not assessed	1.9 Percentage of participants	4.8 Percentage of participants
Percentage of Participants With Best Tumor Response at End of Study Partial Response	21.4 Percentage of participants	4.8 Percentage of participants
Percentage of Participants With Best Tumor Response at End of Study Stable Disease	47.6 Percentage of participants	40.4 Percentage of participants
Percentage of Participants With Best Tumor Response at End of Study Progressive Disease	28.1 Percentage of participants	46.2 Percentage of participants

SECONDARY outcome

Timeframe: Throughout the Study (Up to 5 years)

Population: Safety population included all participants who received at least one dose of study drug.

Number of participants with adverse events as a measure for safety as assessed by the collection of adverse events, laboratory tests for Hematology and Serum Chemistry, clinical assessments and cardiac monitoring.

Outcome measures

Outcome measures
Measure	Trastuzumab + Anastrozole n=103 Participants Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 Participants 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Number of Participants With Adverse Events	90 Participants	68 Participants

Adverse Events

Trastuzumab + Anastrozole

Serious events: 25 serious events

Other events: 89 other events

Deaths: 0 deaths

Anastrozole

Serious events: 6 serious events

Other events: 68 other events

Deaths: 0 deaths

Anastrozole (After Start of Trastuzumab)

Serious events: 8 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Trastuzumab + Anastrozole n=103 participants at risk Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 participants at risk 1 mg oral dose of anastrozole every day for 24 Months in the Main phase.	Anastrozole (After Start of Trastuzumab) n=58 participants at risk 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Gastrointestinal disorders Vomiting	2.9% 3/103	0.00% 0/104	0.00% 0/58
Gastrointestinal disorders Nausea	1.9% 2/103	0.00% 0/104	0.00% 0/58
Gastrointestinal disorders Abdominal pain	0.97% 1/103	0.00% 0/104	0.00% 0/58
Gastrointestinal disorders Constipation	0.97% 1/103	0.00% 0/104	0.00% 0/58
Gastrointestinal disorders Diarrhoea	0.97% 1/103	0.00% 0/104	0.00% 0/58
Gastrointestinal disorders Gastritis	0.97% 1/103	0.00% 0/104	0.00% 0/58
Gastrointestinal disorders Intestinal obstruction	0.97% 1/103	0.00% 0/104	0.00% 0/58
Gastrointestinal disorders Small intestinal obstruction	0.97% 1/103	0.00% 0/104	0.00% 0/58
Infections and infestations Catheter related infection	0.00% 0/103	0.96% 1/104	0.00% 0/58
Infections and infestations Folliculitis	0.97% 1/103	0.00% 0/104	0.00% 0/58
Infections and infestations Lower respiratory tract infection	0.97% 1/103	0.00% 0/104	0.00% 0/58
Infections and infestations Malaria	0.00% 0/103	0.96% 1/104	0.00% 0/58
Infections and infestations Respiratory tract infection	0.00% 0/103	0.96% 1/104	0.00% 0/58
Infections and infestations Streptococcal sepsis	0.97% 1/103	0.00% 0/104	0.00% 0/58
Infections and infestations Urinary tract infection pseudomonal	0.97% 1/103	0.00% 0/104	0.00% 0/58
General disorders Chest pain	2.9% 3/103	0.00% 0/104	0.00% 0/58
General disorders Pain	1.9% 2/103	0.00% 0/104	0.00% 0/58
General disorders Pyrexia	0.97% 1/103	0.96% 1/104	0.00% 0/58
General disorders Asthenia	0.97% 1/103	0.00% 0/104	0.00% 0/58
Injury, poisoning and procedural complications Contusion	0.97% 1/103	0.00% 0/104	0.00% 0/58
Injury, poisoning and procedural complications Fall	0.97% 1/103	0.00% 0/104	0.00% 0/58
Injury, poisoning and procedural complications Femur fracture	0.97% 1/103	0.00% 0/104	0.00% 0/58
Injury, poisoning and procedural complications Hip fracture	0.97% 1/103	0.00% 0/104	0.00% 0/58
Injury, poisoning and procedural complications Humerus fracture	0.97% 1/103	0.00% 0/104	0.00% 0/58
Injury, poisoning and procedural complications Upper limb fracture	0.97% 1/103	0.00% 0/104	0.00% 0/58
Metabolism and nutrition disorders Hypercalcaemia	1.9% 2/103	0.00% 0/104	0.00% 0/58
Metabolism and nutrition disorders Dehydration	0.97% 1/103	0.00% 0/104	0.00% 0/58
Metabolism and nutrition disorders Hyponatraemia	0.97% 1/103	0.00% 0/104	0.00% 0/58
Cardiac disorders Myocardial infarction	0.97% 1/103	0.96% 1/104	0.00% 0/58
Cardiac disorders Myocardial ischaemia	0.97% 1/103	0.00% 0/104	0.00% 0/58
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/103	0.96% 1/104	0.00% 0/58
Musculoskeletal and connective tissue disorders Back pain	0.97% 1/103	0.00% 0/104	0.00% 0/58
Musculoskeletal and connective tissue disorders Pathological fracture	0.97% 1/103	0.00% 0/104	1.7% 1/58
Vascular disorders Hypertension	0.97% 1/103	0.00% 0/104	1.7% 1/58
Vascular disorders Hypotension	0.97% 1/103	0.00% 0/104	0.00% 0/58
Vascular disorders Venous insufficiency	0.97% 1/103	0.00% 0/104	0.00% 0/58
Blood and lymphatic system disorders Febrile neutropenia	0.97% 1/103	0.96% 1/104	0.00% 0/58
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.97% 1/103	0.00% 0/104	0.00% 0/58
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.97% 1/103	0.00% 0/104	0.00% 0/58
Renal and urinary disorders Renal failure acute	0.00% 0/103	0.96% 1/104	0.00% 0/58
Renal and urinary disorders Urinary retention	0.97% 1/103	0.00% 0/104	0.00% 0/58
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.97% 1/103	0.96% 1/104	1.7% 1/58
Ear and labyrinth disorders Middle ear inflammation	0.97% 1/103	0.00% 0/104	0.00% 0/58
Hepatobiliary disorders Cholelithiasis	0.97% 1/103	0.00% 0/104	0.00% 0/58
Nervous system disorders Headache	0.97% 1/103	0.00% 0/104	0.00% 0/58
Psychiatric disorders Depression	0.97% 1/103	0.00% 0/104	0.00% 0/58
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.97% 1/103	0.00% 0/104	0.00% 0/58
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/103	0.00% 0/104	1.7% 1/58
Gastrointestinal disorders Dyspepsia	0.00% 0/103	0.00% 0/104	1.7% 1/58
General disorders Sudden death	0.00% 0/103	0.00% 0/104	1.7% 1/58
Renal and urinary disorders Ureteric obstruction	0.00% 0/103	0.00% 0/104	1.7% 1/58
Skin and subcutaneous tissue disorders Exfoliative rash	0.00% 0/103	0.00% 0/104	1.7% 1/58

Other adverse events

Other adverse events
Measure	Trastuzumab + Anastrozole n=103 participants at risk Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.	Anastrozole n=104 participants at risk 1 mg oral dose of anastrozole every day for 24 Months in the Main phase.	Anastrozole (After Start of Trastuzumab) n=58 participants at risk 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Gastrointestinal disorders Constipation	10.7% 11/103	4.8% 5/104	5.2% 3/58
Gastrointestinal disorders Diarrhoea	19.4% 20/103	7.7% 8/104	13.8% 8/58
Gastrointestinal disorders Nausea	14.6% 15/103	4.8% 5/104	8.6% 5/58
Gastrointestinal disorders Vomiting	20.4% 21/103	4.8% 5/104	8.6% 5/58
General disorders Chills	14.6% 15/103	0.00% 0/104	5.2% 3/58
General disorders Fatigue	21.4% 22/103	9.6% 10/104	6.9% 4/58
General disorders Oedema peripheral	6.8% 7/103	1.9% 2/104	6.9% 4/58
General disorders Pyrexia	16.5% 17/103	5.8% 6/104	6.9% 4/58
Infections and infestations Influenza	6.8% 7/103	3.8% 4/104	1.7% 1/58
Infections and infestations Nasopharyngitis	16.5% 17/103	1.9% 2/104	3.4% 2/58
Investigations Weight decreased	8.7% 9/103	3.8% 4/104	5.2% 3/58
Investigations Weight increased	8.7% 9/103	3.8% 4/104	1.7% 1/58
Metabolism and nutrition disorders Anorexia	6.8% 7/103	1.9% 2/104	5.2% 3/58
Musculoskeletal and connective tissue disorders Arthralgia	14.6% 15/103	8.7% 9/104	5.2% 3/58
Musculoskeletal and connective tissue disorders Back pain	14.6% 15/103	6.7% 7/104	5.2% 3/58
Musculoskeletal and connective tissue disorders Bone pain	10.7% 11/103	5.8% 6/104	3.4% 2/58
Musculoskeletal and connective tissue disorders Musculoskeletal pain	12.6% 13/103	2.9% 3/104	5.2% 3/58
Musculoskeletal and connective tissue disorders Myalgia	2.9% 3/103	1.9% 2/104	6.9% 4/58
Musculoskeletal and connective tissue disorders Pain in extremity	5.8% 6/103	3.8% 4/104	5.2% 3/58
Nervous system disorders Dizziness	9.7% 10/103	3.8% 4/104	3.4% 2/58
Nervous system disorders Headache	13.6% 14/103	5.8% 6/104	3.4% 2/58
Psychiatric disorders Depression	5.8% 6/103	0.96% 1/104	0.00% 0/58
Respiratory, thoracic and mediastinal disorders Cough	14.6% 15/103	5.8% 6/104	6.9% 4/58
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.6% 14/103	8.7% 9/104	6.9% 4/58
Skin and subcutaneous tissue disorders Alopecia	3.9% 4/103	1.9% 2/104	10.3% 6/58
Skin and subcutaneous tissue disorders Rash	5.8% 6/103	5.8% 6/104	1.7% 1/58
Vascular disorders Hot flush	8.7% 9/103	2.9% 3/104	0.00% 0/58
Vascular disorders Hypertension	5.8% 6/103	3.8% 4/104	3.4% 2/58
Blood and lymphatic system disorders Neutropenia	0.00% 0/103	0.00% 0/104	5.2% 3/58
Eye disorders Lacrimation increased	0.97% 1/103	0.00% 0/104	6.9% 4/58
General disorders Mucosal inflammation	4.9% 5/103	0.00% 0/104	6.9% 4/58

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Results disclosure agreements

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

Restriction type: OTHER