Trial Outcomes & Findings for Safety and Efficacy of Trastuzumab as Part of Breast Cancer Treatment Regimen (NCT NCT02419742)

NCT ID: NCT02419742

Last Updated: 2022-10-12

Results Overview

LVEF assessments were performed every three months (four cycles) using echocardiogram

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 110 participants
• Primary outcome timeframe: Baseline to every 4 cycles up to Cycle 21 (AC-TH), every 4 cycles up to Cycle 17 (TCH) (each cycle is 21 days), at study treatment completion (12 months post baseline) at 6 month (18 months post baseline) and 12 month follow-up (24 months post baseline)
• Results posted on: 2022-10-12

Participant Flow

The study was conducted at 6 investigational sites in India.

Of the 110 participants enrolled, 108 received at least one dose of trastuzumab and were included in the safety population.

Participant milestones

Measure	Trastuzumab With AC-TH Regimen Participants received trastuzumab with AC-TH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. AC-TH regimen consisted of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.	Trastuzumab With TCH Regimen Participants received trastuzumab with TCH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. TCH consisted of docetaxel and carboplatin. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.
Overall Study STARTED	58	52
Overall Study COMPLETED	53	50
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Measure	Trastuzumab With AC-TH Regimen Participants received trastuzumab with AC-TH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. AC-TH regimen consisted of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.	Trastuzumab With TCH Regimen Participants received trastuzumab with TCH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. TCH consisted of docetaxel and carboplatin. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.
Overall Study Adverse Event	2	0
Overall Study Disease Progression	0	1
Overall Study Withdrew Consent	2	1
Overall Study Any other reason which the Investigator deemed participant unsuitable for enrollment into the study	1	0

Baseline Characteristics

Safety and Efficacy of Trastuzumab as Part of Breast Cancer Treatment Regimen

Baseline characteristics by cohort

Measure	Trastuzumab With AC-TH Regimen n=58 Participants Participants received trastuzumab with AC-TH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. AC-TH regimen consisted of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.	Trastuzumab With TCH Regimen n=52 Participants Participants received trastuzumab with TCH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. TCH consisted of docetaxel and carboplatin. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.	Total n=110 Participants Total of all reporting groups
Age, Continuous	51.95 Years STANDARD_DEVIATION 7.96 • n=5 Participants	51.19 Years STANDARD_DEVIATION 10.94 • n=7 Participants	51.59 Years STANDARD_DEVIATION 9.45 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	52 Participants n=7 Participants	110 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	58 Participants n=5 Participants	52 Participants n=7 Participants	110 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to every 4 cycles up to Cycle 21 (AC-TH), every 4 cycles up to Cycle 17 (TCH) (each cycle is 21 days), at study treatment completion (12 months post baseline) at 6 month (18 months post baseline) and 12 month follow-up (24 months post baseline)

Population: Safety Population included all enrolled participants who received at least one dose of study medication.

LVEF assessments were performed every three months (four cycles) using echocardiogram

Outcome measures

Measure	Trastuzumab With AC-TH Regimen n=56 Participants Participants received trastuzumab with AC-TH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. AC-TH regimen consisted of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.	Trastuzumab With TCH Regimen n=52 Participants Participants received trastuzumab with TCH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. TCH consisted of docetaxel and carboplatin. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography Study Completion Visit	-3.3 Percentage of LVEF Standard Deviation 6.59	-0.7 Percentage of LVEF Standard Deviation 2.72
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography Baseline	60.1 Percentage of LVEF Standard Deviation 6.17	62.1 Percentage of LVEF Standard Deviation 2.30
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography Cycle 5	-0.2 Percentage of LVEF Standard Deviation 4.71	-0.4 Percentage of LVEF Standard Deviation 2.72
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography Cycle 9	-0.5 Percentage of LVEF Standard Deviation 4.64	-1.0 Percentage of LVEF Standard Deviation 2.98
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography Cycle 13	-2.0 Percentage of LVEF Standard Deviation 6.94	-1.0 Percentage of LVEF Standard Deviation 2.36
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography Cycle 17	-1.8 Percentage of LVEF Standard Deviation 4.77	-1.1 Percentage of LVEF Standard Deviation 3.15
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography Cycle 21	-1.8 Percentage of LVEF Standard Deviation 4.88	—
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography 6 Month Follow Up	-1.6 Percentage of LVEF Standard Deviation 5.89	-0.3 Percentage of LVEF Standard Deviation 3.18
Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography 12 Month Follow Up	-2.2 Percentage of LVEF Standard Deviation 6.28	-0.4 Percentage of LVEF Standard Deviation 2.92

PRIMARY outcome

Timeframe: Baseline up to approximately 5 years and 10 months

Population: Safety Population included all enrolled participants who received at least one dose of study medication.

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events.

Outcome measures

Measure	Trastuzumab With AC-TH Regimen n=56 Participants Participants received trastuzumab with AC-TH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. AC-TH regimen consisted of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.	Trastuzumab With TCH Regimen n=52 Participants Participants received trastuzumab with TCH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. TCH consisted of docetaxel and carboplatin. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.
Percentage of Participants With Adverse Events	46 Participants	51 Participants

SECONDARY outcome

Timeframe: The date of first study treatment to the date of local, regional or distant recurrence, contra-lateral breast cancer or death due to any cause within 12 months from the last dose of Trastuzumab for every participant

Population: ITT population included all participants enrolled in the study.

DFS was defined as time from the date of first study treatment to the date of local, regional or distant recurrence, contra-lateral breast cancer or death due to any cause. Local, regional or distant recurrence, and contra-lateral breast cancer was assessed by combination of physical examination, mammography and pelvic examination.

Outcome measures

Measure	Trastuzumab With AC-TH Regimen n=58 Participants Participants received trastuzumab with AC-TH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. AC-TH regimen consisted of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.	Trastuzumab With TCH Regimen n=52 Participants Participants received trastuzumab with TCH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. TCH consisted of docetaxel and carboplatin. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.
Disease Free Survival (DFS)	NA Months The median duration of DFS was not estimable as there were no disease progression during the study period.	NA Months The median duration of DFS was not estimable as there were no disease progression during the study period.

SECONDARY outcome

Timeframe: Time from the date of first study treatment until date of death, regardless of the cause of death within 12 months from the last dose of Trastuzumab for every participant. The follow up period was 52 weeks from the last dose of treatment in both arms.

Population: ITT population included all participants enrolled in the study.

Overall survival was defined as time from the date of first study treatment until date of death, regardless of the cause of death.

Outcome measures

Measure	Trastuzumab With AC-TH Regimen n=58 Participants Participants received trastuzumab with AC-TH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. AC-TH regimen consisted of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.	Trastuzumab With TCH Regimen n=52 Participants Participants received trastuzumab with TCH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. TCH consisted of docetaxel and carboplatin. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.
Overall Survival (OS)	NA Months The median duration of OS was not estimable because no deaths were reported during the study. The deaths occurred during the monitoring period of adverse events for the overall study, but not during the overall survival time frame and were censored for OS analysis.	NA Months The median duration of OS was not estimable because no deaths were reported during the study. The deaths occurred during the monitoring period of adverse events for the overall study, but not during the overall survival time frame and were censored for OS analysis.

Adverse Events

Trastuzumab With AC-TH Regimen

Serious events: 11 serious events

Other events: 46 other events

Deaths: 1 deaths

Trastuzumab With TCH Regimen

Serious events: 9 serious events

Other events: 51 other events

Deaths: 1 deaths

Serious adverse events

Measure	Trastuzumab With AC-TH Regimen n=56 participants at risk Participants received trastuzumab with AC-TH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. AC-TH regimen consisted of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.	Trastuzumab With TCH Regimen n=52 participants at risk Participants received trastuzumab with TCH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. TCH consisted of docetaxel and carboplatin. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.
Blood and lymphatic system disorders Anaemia	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	1.9% 1/52 • Number of events 1 • Baseline up to approximately 5 years and 10 months
Blood and lymphatic system disorders Febrile neutropenia	3.6% 2/56 • Number of events 2 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Blood and lymphatic system disorders Neutropenia	3.6% 2/56 • Number of events 2 • Baseline up to approximately 5 years and 10 months	1.9% 1/52 • Number of events 1 • Baseline up to approximately 5 years and 10 months
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	1.9% 1/52 • Number of events 1 • Baseline up to approximately 5 years and 10 months
Cardiac disorders Angina pectoris	1.8% 1/56 • Number of events 1 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Gastrointestinal disorders Diarrhoea	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	3.8% 2/52 • Number of events 2 • Baseline up to approximately 5 years and 10 months
Gastrointestinal disorders Intestinal obstruction	1.8% 1/56 • Number of events 1 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Gastrointestinal disorders Vomiting	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	1.9% 1/52 • Number of events 1 • Baseline up to approximately 5 years and 10 months
General disorders Disease progression	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	3.8% 2/52 • Number of events 2 • Baseline up to approximately 5 years and 10 months
General disorders Fatigue	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	1.9% 1/52 • Number of events 1 • Baseline up to approximately 5 years and 10 months
General disorders Pyrexia	3.6% 2/56 • Number of events 2 • Baseline up to approximately 5 years and 10 months	1.9% 1/52 • Number of events 1 • Baseline up to approximately 5 years and 10 months
Infections and infestations Catheter site infection	1.8% 1/56 • Number of events 1 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Infections and infestations Rectal abscess	1.8% 1/56 • Number of events 1 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Infections and infestations Septic shock	1.8% 1/56 • Number of events 1 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Infections and infestations Urinary tract infection	1.8% 1/56 • Number of events 1 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Infections and infestations Viral infection	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	1.9% 1/52 • Number of events 1 • Baseline up to approximately 5 years and 10 months
Investigations Ejection fraction decreased	1.8% 1/56 • Number of events 1 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Metabolism and nutrition disorders Hyponatremia	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	1.9% 1/52 • Number of events 2 • Baseline up to approximately 5 years and 10 months
Vascular disorders Jugular vein thrombosis	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	1.9% 1/52 • Number of events 1 • Baseline up to approximately 5 years and 10 months

Other adverse events

Measure	Trastuzumab With AC-TH Regimen n=56 participants at risk Participants received trastuzumab with AC-TH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. AC-TH regimen consisted of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.	Trastuzumab With TCH Regimen n=52 participants at risk Participants received trastuzumab with TCH regimen. The choice of the regimen was based on the investigator's discretion referring the local prescribing document of trastuzumab. TCH consisted of docetaxel and carboplatin. Trastuzumab was common in both treatment regimens and was administered weekly or every 3 weeks, as per investigator discretion. Each cycle was 3 weeks.
Blood and lymphatic system disorders Leukopenia	39.3% 22/56 • Number of events 56 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 3 • Baseline up to approximately 5 years and 10 months
Infections and infestations Urinary tract infection	25.0% 14/56 • Number of events 23 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 3 • Baseline up to approximately 5 years and 10 months
General disorders Pyrexia	21.4% 12/56 • Number of events 18 • Baseline up to approximately 5 years and 10 months	21.2% 11/52 • Number of events 15 • Baseline up to approximately 5 years and 10 months
Blood and lymphatic system disorders Anaemia	21.4% 12/56 • Number of events 19 • Baseline up to approximately 5 years and 10 months	51.9% 27/52 • Number of events 44 • Baseline up to approximately 5 years and 10 months
Respiratory, thoracic and mediastinal disorders Cough	12.5% 7/56 • Number of events 10 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 5 • Baseline up to approximately 5 years and 10 months
Nervous system disorders Peripheral motor neuropathy	10.7% 6/56 • Number of events 7 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Blood and lymphatic system disorders Neutropenia	8.9% 5/56 • Number of events 6 • Baseline up to approximately 5 years and 10 months	7.7% 4/52 • Number of events 9 • Baseline up to approximately 5 years and 10 months
Investigations Ejection fraction decreased	8.9% 5/56 • Number of events 6 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Blood and lymphatic system disorders Febrile neutropenia	5.4% 3/56 • Number of events 3 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Gastrointestinal disorders Diarrhoea	5.4% 3/56 • Number of events 4 • Baseline up to approximately 5 years and 10 months	17.3% 9/52 • Number of events 11 • Baseline up to approximately 5 years and 10 months
General disorders Fatigue	5.4% 3/56 • Number of events 3 • Baseline up to approximately 5 years and 10 months	15.4% 8/52 • Number of events 11 • Baseline up to approximately 5 years and 10 months
General disorders Pain	5.4% 3/56 • Number of events 4 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 5 • Baseline up to approximately 5 years and 10 months
Infections and infestations Paronychia	5.4% 3/56 • Number of events 4 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Musculoskeletal and connective tissue disorders Pain in extremity	5.4% 3/56 • Number of events 3 • Baseline up to approximately 5 years and 10 months	19.2% 10/52 • Number of events 11 • Baseline up to approximately 5 years and 10 months
Nervous system disorders Paraesthesia	5.4% 3/56 • Number of events 3 • Baseline up to approximately 5 years and 10 months	13.5% 7/52 • Number of events 8 • Baseline up to approximately 5 years and 10 months
Nervous system disorders Peripheral sensory neuropathy	5.4% 3/56 • Number of events 3 • Baseline up to approximately 5 years and 10 months	0.00% 0/52 • Baseline up to approximately 5 years and 10 months
Skin and subcutaneous tissue disorders Pruritus	5.4% 3/56 • Number of events 3 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 3 • Baseline up to approximately 5 years and 10 months
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	42.3% 22/52 • Number of events 30 • Baseline up to approximately 5 years and 10 months
General disorders Asthenia	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	23.1% 12/52 • Number of events 14 • Baseline up to approximately 5 years and 10 months
Gastrointestinal disorders Vomiting	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	17.3% 9/52 • Number of events 11 • Baseline up to approximately 5 years and 10 months
Reproductive system and breast disorders Breast pain	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	15.4% 8/52 • Number of events 13 • Baseline up to approximately 5 years and 10 months
Skin and subcutaneous tissue disorders Skin reaction	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	15.4% 8/52 • Number of events 9 • Baseline up to approximately 5 years and 10 months
Gastrointestinal disorders Abdominal pain	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	13.5% 7/52 • Number of events 9 • Baseline up to approximately 5 years and 10 months
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	13.5% 7/52 • Number of events 8 • Baseline up to approximately 5 years and 10 months
Nervous system disorders Headache	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	13.5% 7/52 • Number of events 7 • Baseline up to approximately 5 years and 10 months
Gastrointestinal disorders Constipation	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	11.5% 6/52 • Number of events 6 • Baseline up to approximately 5 years and 10 months
Ear and labyrinth disorders Vertigo	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	11.5% 6/52 • Number of events 7 • Baseline up to approximately 5 years and 10 months
General disorders Peripheral swelling	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	7.7% 4/52 • Number of events 4 • Baseline up to approximately 5 years and 10 months
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	7.7% 4/52 • Number of events 4 • Baseline up to approximately 5 years and 10 months
Nervous system disorders Hypoaesthesia	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	7.7% 4/52 • Number of events 5 • Baseline up to approximately 5 years and 10 months
Psychiatric disorders Insomnia	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	7.7% 4/52 • Number of events 4 • Baseline up to approximately 5 years and 10 months
Vascular disorders Hypertension	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	7.7% 4/52 • Number of events 4 • Baseline up to approximately 5 years and 10 months
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 3 • Baseline up to approximately 5 years and 10 months
Nervous system disorders Dizziness	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 3 • Baseline up to approximately 5 years and 10 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 3 • Baseline up to approximately 5 years and 10 months
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 3 • Baseline up to approximately 5 years and 10 months
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 4 • Baseline up to approximately 5 years and 10 months
Skin and subcutaneous tissue disorders Rash	0.00% 0/56 • Baseline up to approximately 5 years and 10 months	5.8% 3/52 • Number of events 3 • Baseline up to approximately 5 years and 10 months

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

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