Trial Outcomes & Findings for An Observational Study of Patients With HER2-Positive Metastatic or Locally Advanced Breast Cancer Treated With Herceptin (Trastuzumab) in 1st Line and Without Progression For 3 Years (NCT NCT01480674)

Last Updated: 2017-08-16

Results Overview

The clinical and tumor characteristics including HER2 and Hormone Receptor (HR) status of metastatic breast cancer participants are analysed which are important factors which impact on Progression Free Survival.

Recruitment status

COMPLETED

Target enrollment

160 participants

Primary outcome timeframe

Up to 3 years

Results posted on

2017-08-16

Participant Flow

A total of 160 participants were recruited from 28 March 2011 to 16 November 2012.

Participant milestones

Participant milestones
Measure	Trastuzumab Eligible participants with human epidermal growth factor receptor 2 (HER2)-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab (Herceptin) as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Overall Study STARTED	160
Overall Study Safety Set	154
Overall Study Analysed Set	128
Overall Study COMPLETED	125
Overall Study NOT COMPLETED	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Trastuzumab Eligible participants with human epidermal growth factor receptor 2 (HER2)-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab (Herceptin) as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Overall Study Death	23
Overall Study Lost to Follow-up	2
Overall Study visit not done	10

Baseline Characteristics

An Observational Study of Patients With HER2-Positive Metastatic or Locally Advanced Breast Cancer Treated With Herceptin (Trastuzumab) in 1st Line and Without Progression For 3 Years

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trastuzumab n=128 Participants Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Age, Continuous	61.3 Years STANDARD_DEVIATION 12.2 • n=93 Participants
Sex: Female, Male Female	128 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: Up to 3 years

Population: Analyzed set population included all enrolled participants without any protocol deviation. This population set was used as a primary analysis population for all efficacy outcome measures. Participants with available data at the time of evaluation were reported.

Outcome measures

Outcome measures
Measure	Trastuzumab n=125 Participants Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Tumor Hormone Receptor Status of Participants Without Progression HR Positive	57.6 Percentage of participants Interval 48.8 to 65.9
Tumor Hormone Receptor Status of Participants Without Progression HR Negative	42.4 Percentage of participants Interval 34.1 to 51.2

PRIMARY outcome

Timeframe: Up to 3 years

Bone metastasis occurs when cancer cells spread from their original site to a bone. Percentage of participants with prevalence of bone metastases without progression were reported

Outcome measures

Outcome measures
Measure	Trastuzumab n=127 Participants Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Percentage of Participants With Prevalence of Bone Metastases Without Progression for at Least 3 Years After the Beginning of 1st Line Herceptin Treatment	42.5 Percentage of participants Interval 34.3 to 51.2

SECONDARY outcome

Timeframe: Up to 12 years

Population: Analyzed set population included all enrolled participants without any protocol deviation. This population set was used as a primary analysis population for all efficacy outcome measures.

The Progression-free survival (PFS) was defined as the time between the treatment start date (date of first trastuzumab infusion during the metastatic period) and the date of the first progressive disease or death from any cause. The method of assessment of disease progression was not outlined within the protocol, this was completed by each investigator in line with routine practice.

Outcome measures

Outcome measures
Measure	Trastuzumab n=128 Participants Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Progression-free Survival	6.44 Years Interval 5.68 to The value was not evaluated.

SECONDARY outcome

Timeframe: Up to 12 years

Population: Analyzed set population included all enrolled participants without any protocol deviation. This population set was used as a primary analysis population for all efficacy outcome measures.

The Time to progression (TTP) was defined as the time between the treatment start date (date of the first trastuzumab infusion during the metastatic period) and the date of the first progressive disease.

Outcome measures

Outcome measures
Measure	Trastuzumab n=128 Participants Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Time to Progression	6.44 Years Interval 5.77 to The value was not evaluated.

SECONDARY outcome

Timeframe: Up to 12 years

Population: Analyzed set population included all enrolled participants without any protocol deviation. This population set was used as a primary analysis population for all efficacy outcome measures.

The overall survival (OS) was defined as the time between the treatment start date (date of the first trastuzumab infusion during the metastatic period) and the death from any cause.

Outcome measures

Outcome measures
Measure	Trastuzumab n=128 Participants Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Overall Survival	NA Years Median OS not achieved (only 12.5% of participants died).

SECONDARY outcome

Timeframe: Up to 12 years

Participants who received trastuzumab are reported in the below table. The regimen of trastuzumab in first line treatment is presented as in frequency 1 infusion (inf) per week (W) and dose per infusion as mg/kg.

Outcome measures

Outcome measures
Measure	Trastuzumab n=125 Participants Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Dosage Schedule of Herceptin Treatment Dose and frequency of inf:1 inf / W, n= 125	40 Participants
Dosage Schedule of Herceptin Treatment 1 inf/2W, n= 125	2 Participants
Dosage Schedule of Herceptin Treatment 1 inf / 3W, n= 125	82 Participants
Dosage Schedule of Herceptin Treatment 3 inf/4W, n= 125	1 Participants
Dosage Schedule of Herceptin Treatment Dose per inf: 2 mg/kg, n= 124	10 Participants
Dosage Schedule of Herceptin Treatment 3 mg/kg, n= 124	1 Participants
Dosage Schedule of Herceptin Treatment 4 mg/kg, n= 124	39 Participants
Dosage Schedule of Herceptin Treatment 6 mg/kg, n= 124	25 Participants
Dosage Schedule of Herceptin Treatment 8 mg/kg, n= 124	49 Participants

SECONDARY outcome

Timeframe: Up to 12 years

Antineoplastic treatment given in combination with and after discontinuation (Aft. Dis) of herceptin treatment included chemotherapy and hormonotherapy.

Outcome measures

Outcome measures
Measure	Trastuzumab n=128 Participants Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Number of Participants With Antineoplastic Treatment in Combination With Trastuzumab and After Discontinuation of Trastuzumab Treatment With Trastuzumab, Chemotherapy, n= 119	117 Participants
Number of Participants With Antineoplastic Treatment in Combination With Trastuzumab and After Discontinuation of Trastuzumab Treatment With Trastuzumab, Hormonotherapy, n= 51	50 Participants
Number of Participants With Antineoplastic Treatment in Combination With Trastuzumab and After Discontinuation of Trastuzumab Treatment Aft. Dis, Chemotherapy n= 128	22 Participants
Number of Participants With Antineoplastic Treatment in Combination With Trastuzumab and After Discontinuation of Trastuzumab Treatment Aft. Dis, hormonotherapy n= 128	4 Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: The safety population set included of all participants who received at least one dose of study drug. Participants with available data in the prospective period were analysed.

An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. The data was reported for prospective period.

Outcome measures

Outcome measures
Measure	Trastuzumab n=134 Participants Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Number of Participants With Any Adverse Events and Serious Adverse Events Any AEs	30 Participants
Number of Participants With Any Adverse Events and Serious Adverse Events Any SAEs	6 Participants

SECONDARY outcome

Timeframe: Up to 1 Year

Population: Analyzed Set population included all enrolled participants without any protocol deviation used as a primary analysis population for all efficacy outcome measures.

Total treatment duration and duration of the first line of treatment is reported.

Outcome measures

Outcome measures
Measure	Trastuzumab n=128 Participants Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
The Duration of Treatment of Trastuzumab First line of treatment	4.89 Years Standard Deviation 2.13
The Duration of Treatment of Trastuzumab Total treatment duration	5.57 Years Standard Deviation 2.36

Adverse Events

Trastuzumab

Serious events: 6 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Trastuzumab n=134 participants at risk Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Nervous system disorders Paraplegia	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Nervous system disorders Coma	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Injury, poisoning and procedural complications Femoral neck fracture	1.5% 2/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Cardiac disorders Cardiac failure congestive	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Vascular disorders Lymphoedema	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.

Other adverse events

Other adverse events
Measure	Trastuzumab n=134 participants at risk Eligible participants with HER2-positive metastatic or locally advanced breast cancer, who were treated with trastuzumab as a first-line therapy and were progression-free for at least 3 years after treatment initiation, were included and were followed for one year.
Blood and lymphatic system disorders Leukopenia	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Blood and lymphatic system disorders Lymphopenia	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Cardiac disorders Atrioventricular extrasystoles	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Cardiac disorders Left ventricular dysfunction	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Ear and labyrinth disorders Deafness	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Ear and labyrinth disorders Tinnitus	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Ear and labyrinth disorders Vertigo	2.2% 3/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Endocrine disorders Cushing's syndrome	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Gastrointestinal disorders Abdominal pain	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Gastrointestinal disorders Abdominal pain upper	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Gastrointestinal disorders Aphthous stomatitis	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Gastrointestinal disorders Diarrhoea	3.7% 5/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Gastrointestinal disorders Gastrooesophageal reflux disease	1.5% 2/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Gastrointestinal disorders Gingival bleeding	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Gastrointestinal disorders Gingivitis	1.5% 2/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Gastrointestinal disorders Nausea	2.2% 3/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Gastrointestinal disorders Rectal haemorrhage	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Gastrointestinal disorders Vomiting	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
General disorders Asthenia	4.5% 6/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
General disorders Chest discomfort	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
General disorders Chest pain	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
General disorders Fatigue	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
General disorders Mucosal inflammation	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
General disorders Oedema	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
General disorders Oedema peripheral	1.5% 2/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Hepatobiliary disorders Cytolytic hepatitis	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Infections and infestations Erysipelas	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Infections and infestations Herpes virus infection	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Infections and infestations Sinobronchitis	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Infections and infestations Urinary tract infection	2.2% 3/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Injury, poisoning and procedural complications Radiation skin injury	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Injury, poisoning and procedural complications Rib fracture	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Investigations Alanine aminotransferase increased	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Investigations Aspartate aminotransferase increased	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Investigations Blood alkaline phosphatase increased	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Investigations Blood glucose	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Investigations Blood sodium	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Investigations Ejection fraction decreased	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Investigations Gamma-glutamyltransferase	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Investigations Gamma-glutamyltransferase increased	1.5% 2/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Metabolism and nutrition disorders Hypercalcaemia	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Metabolism and nutrition disorders Hypercreatininaemia	1.5% 2/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Metabolism and nutrition disorders Hyperglycaemia	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Metabolism and nutrition disorders Hypocalcaemia	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Metabolism and nutrition disorders Hypoglycaemia	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Metabolism and nutrition disorders Hypokalaemia	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Metabolism and nutrition disorders Hyponatraemia	1.5% 2/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Musculoskeletal and connective tissue disorders Arthralgia	2.2% 3/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Musculoskeletal and connective tissue disorders Back pain	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.5% 2/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Musculoskeletal and connective tissue disorders Myalgia	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Musculoskeletal and connective tissue disorders Pain in extremity	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Musculoskeletal and connective tissue disorders Periarthritis	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Nervous system disorders Brain oedema	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Nervous system disorders Headache	2.2% 3/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Nervous system disorders Neuropathy peripheral	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Nervous system disorders Paraesthesia	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Nervous system disorders Paresis	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Nervous system disorders Sciatic nerve neuropathy	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Nervous system disorders Sciatica	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Skin and subcutaneous tissue disorders Erythema	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	3.0% 4/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Skin and subcutaneous tissue disorders Rosacea	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Skin and subcutaneous tissue disorders Skin exfoliation	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Skin and subcutaneous tissue disorders Skin fissures	1.5% 2/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Surgical and medical procedures Cataract operation	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Surgical and medical procedures Mastectomy	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Vascular disorders Ischaemic limb pain	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Vascular disorders Lymphoedema	1.5% 2/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Vascular disorders Subclavian vein thrombosis	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Vascular disorders Thrombophlebitis superficial	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.
Vascular disorders Vascular compression	0.75% 1/134 • Up to 1 year An AE is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug .The data was reported for prospective period. Participants with available data in the prospective period were analysed.

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 616878333

Email: [email protected]

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