Trial Outcomes & Findings for Safety Study of Pertuzumab (in Combination With Trastuzumab and Docetaxel) in Indian Participants With Breast Cancer (NCT NCT02445586)

NCT ID: NCT02445586

Last Updated: 2019-10-29

Results Overview

The number of participants with serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (\>) 1, or 0 serious adverse events. Participants with multiple occurrences of events (the ≥1 and \>1 serious adverse event categories) were only counted once per category.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 52 participants
• Primary outcome timeframe: From Baseline until end of study (up to approximately 3 years)
• Results posted on: 2019-10-29

Participant Flow

Participant milestones

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Study STARTED	52
Overall Study Received at Least One Dose of Study Drug	52
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	39

Reasons for withdrawal

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Study Death	14
Overall Study Withdrawal by Subject	13
Overall Study Disease Progression	10
Overall Study Protocol Violation	1
Overall Study Medical Condition	1

Baseline Characteristics

Safety Study of Pertuzumab (in Combination With Trastuzumab and Docetaxel) in Indian Participants With Breast Cancer

Baseline characteristics by cohort

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Age, Continuous	50.2 years STANDARD_DEVIATION 9.05 • n=93 Participants
Sex: Female, Male Female	52 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Race/Ethnicity, Customized Race: Asian	52 Participants n=93 Participants
Race/Ethnicity, Customized Ethnicity: Indian Subcontinent	52 Participants n=93 Participants
Diagnosis of Metastatic or Locally Recurrent Breast Cancer Metastatic	52 Participants n=93 Participants
Diagnosis of Metastatic or Locally Recurrent Breast Cancer Locally Recurrent	0 Participants n=93 Participants
Histological Grade of Breast Cancer Well Differentiated	14 Participants n=93 Participants
Histological Grade of Breast Cancer Moderately Differentiated	16 Participants n=93 Participants
Histological Grade of Breast Cancer Poorly Differentiated	11 Participants n=93 Participants
Histological Grade of Breast Cancer Anaplastic	0 Participants n=93 Participants
Histological Grade of Breast Cancer Unknown	11 Participants n=93 Participants
Breast Cancer Subtype by Histology Ductal	47 Participants n=93 Participants
Breast Cancer Subtype by Histology Lobular	0 Participants n=93 Participants
Breast Cancer Subtype by Histology Other	5 Participants n=93 Participants
Presence or Absence of Ductal Carcinoma In Situ (DCIS) DCIS Present	22 Participants n=93 Participants
Presence or Absence of Ductal Carcinoma In Situ (DCIS) DCIS Absent	29 Participants n=93 Participants
Presence or Absence of Ductal Carcinoma In Situ (DCIS) DCIS Assessment Missing	1 Participants n=93 Participants
HER2-Positive Breast Cancer Confirmation Method Immunohistochemistry (IHC)	31 Participants n=93 Participants
HER2-Positive Breast Cancer Confirmation Method In Situ Hybridization (ISH)	1 Participants n=93 Participants
HER2-Positive Breast Cancer Confirmation Method Both IHC and ISH	20 Participants n=93 Participants
HER2 Expression Score by IHC 0	0 Participants n=93 Participants
HER2 Expression Score by IHC 1+	0 Participants n=93 Participants
HER2 Expression Score by IHC 2+	4 Participants n=93 Participants
HER2 Expression Score by IHC 3+	47 Participants n=93 Participants
HER2 Expression Score by IHC Assessment Missing	1 Participants n=93 Participants
HER2 Expression Score by ISH Negative (Non-Amplified)	1 Participants n=93 Participants
HER2 Expression Score by ISH Positive (Amplified)	20 Participants n=93 Participants
HER2 Expression Score by ISH Not Assessed by ISH	31 Participants n=93 Participants
Hormone Receptor Status (Positive or Negative) Estrogen Receptor · Positive	21 Participants n=93 Participants
Hormone Receptor Status (Positive or Negative) Estrogen Receptor · Negative	31 Participants n=93 Participants
Hormone Receptor Status (Positive or Negative) Progesterone Receptor · Positive	18 Participants n=93 Participants
Hormone Receptor Status (Positive or Negative) Progesterone Receptor · Negative	34 Participants n=93 Participants
Any Previous Therapy for Breast Cancer Yes	19 Participants n=93 Participants
Any Previous Therapy for Breast Cancer No	33 Participants n=93 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (>) 1, or 0 serious adverse events. Participants with multiple occurrences of events (the ≥1 and >1 serious adverse event categories) were only counted once per category.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant ≥1 Serious Adverse Event	31 Participants
Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant 1 Serious Adverse Event	17 Participants
Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant >1 Serious Adverse Events	14 Participants
Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant 0 Serious Adverse Events	21 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population; the number analyzed in each category represents the number of participants with at least one serious adverse event (denominator).

The number of participants with serious adverse events was counted by the initial and most extreme levels of severity of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of serious adverse events of the same severity were only counted once per severity category.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) Initial Severity - Grade 1	1 Participants
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) Initial Severity - Grade 2	4 Participants
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) Initial Severity - Grade 3	15 Participants
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) Initial Severity - Grade 4	7 Participants
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) Initial Severity - Grade 5	14 Participants
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) Most Extreme Severity - Grade 1	1 Participants
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) Most Extreme Severity - Grade 2	3 Participants
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) Most Extreme Severity - Grade 3	16 Participants
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) Most Extreme Severity - Grade 4	7 Participants
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) Most Extreme Severity - Grade 5	15 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with docetaxel, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Serious Adverse Events Related to Docetaxel Any Serious AEs Related to Docetaxel	15 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Diarrhoea	5 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Left ventricular dysfunction	2 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Fatigue	2 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Sinus tachycardia	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Abdominal pain	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Febrile neutropenia	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Enteritis	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Salivary hypersecretion	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Stomatitis	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Vomiting	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Pyrexia	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Device related sepsis	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Septic shock	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Infusion related reaction	1 Participants
Number of Participants With Serious Adverse Events Related to Docetaxel Rash	1 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with pertuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Serious Adverse Events Related to Pertuzumab Any Serious AEs Related to Pertuzumab	13 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Diarrhoea	4 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Ejection fraction decreased	3 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Left ventricular dysfunction	2 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Sinus tachycardia	1 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Abdominal pain	1 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Enteritis	1 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Stomatitis	1 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Fatigue	1 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Pyrexia	1 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Gastroenteritis	1 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Dyspnoea	1 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Rash	1 Participants
Number of Participants With Serious Adverse Events Related to Pertuzumab Shock	1 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with trastuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Serious Adverse Events Related to Trastuzumab Shock	1 Participants
Number of Participants With Serious Adverse Events Related to Trastuzumab Any Serious AEs Related to Trastuzumab	10 Participants
Number of Participants With Serious Adverse Events Related to Trastuzumab Ejection fraction decreased	3 Participants
Number of Participants With Serious Adverse Events Related to Trastuzumab Left ventricular dysfunction	2 Participants
Number of Participants With Serious Adverse Events Related to Trastuzumab Diarrhoea	2 Participants
Number of Participants With Serious Adverse Events Related to Trastuzumab Enteritis	1 Participants
Number of Participants With Serious Adverse Events Related to Trastuzumab Fatigue	1 Participants
Number of Participants With Serious Adverse Events Related to Trastuzumab Pyrexia	1 Participants
Number of Participants With Serious Adverse Events Related to Trastuzumab Sinus tachycardia	1 Participants
Number of Participants With Serious Adverse Events Related to Trastuzumab Rash	1 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population; the number analyzed represents participants with at least one serious adverse event (denominator).

The number of participants with serious adverse events was counted by the type of action taken with the study drug (docetaxel, pertuzumab, and trastuzumab) in response to the adverse event in the three following categories: infusion reduced, temporarily interrupted, or permanently discontinued. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events that required the same action to be taken with the study drug were only counted once per category.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug Infusion of Docetaxel Reduced	0 Participants
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug Infusion of Docetaxel Temporarily Interrupted	1 Participants
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug Infusion of Docetaxel Permanently Discontinued	1 Participants
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug Infusion of Pertuzumab Reduced	0 Participants
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug Infusion of Pertuzumab Temporarily Interrupted	3 Participants
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug Infusion of Pertuzumab Permanently Discontinued	4 Participants
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug Infusion of Trastuzumab Reduced	0 Participants
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug Infusion of Trastuzumab Temporarily Interrupted	3 Participants
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug Infusion of Trastuzumab Permanently Discontinued	5 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population; the number analyzed represents participants with at least one serious adverse event (denominator).

The number of participants with serious adverse events was counted by the event outcome in the six following categories: fatal, recovered/resolved, recovered/resolved with sequelae, recovering/resolving, not recovered/not resolved, or unknown. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events with the same outcome were only counted once per category.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Number of Participants With Serious Adverse Events by Event Outcome Fatal	15 Participants
Overall Number of Participants With Serious Adverse Events by Event Outcome Recovered / Resolved	18 Participants
Overall Number of Participants With Serious Adverse Events by Event Outcome Recovered / Resolved with Sequelae	1 Participants
Overall Number of Participants With Serious Adverse Events by Event Outcome Recovering / Resolving	3 Participants
Overall Number of Participants With Serious Adverse Events by Event Outcome Not Recovered / Not Resolved	2 Participants
Overall Number of Participants With Serious Adverse Events by Event Outcome Unknown	0 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with hematological laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Hematological Abnormalities Reported as Serious Adverse Events	2 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with serum chemistry laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Serum Chemistry Abnormalities Reported as Serious Adverse Events	0 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with coagulation laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Coagulation Abnormalities Reported as Serious Adverse Events	1 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants who died due to a serious adverse event was counted by the cause of death.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death Disease progression	10 Participants
Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death Sepsis and disease progression	1 Participants
Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death Dyspnoea	1 Participants
Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death Septic shock	1 Participants
Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death Shock	1 Participants
Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death Unknown cause	1 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with non-serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (>) 1, or 0 non-serious adverse events. Participants with multiple occurrences of events (the ≥1 and >1 non-serious adverse event categories) were only counted once per category.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Number of Participants by the Number of Non-Serious Adverse Events Reported Per Participant 1 Non-Serious Adverse Event	11 Participants
Overall Number of Participants by the Number of Non-Serious Adverse Events Reported Per Participant ≥1 Non-Serious Adverse Event	47 Participants
Overall Number of Participants by the Number of Non-Serious Adverse Events Reported Per Participant >1 Non-Serious Adverse Events	36 Participants
Overall Number of Participants by the Number of Non-Serious Adverse Events Reported Per Participant 0 Non-Serious Adverse Events	5 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population; the number analyzed represents participants with at least one non-serious adverse event (denominator).

The number of participants with non-serious adverse events was counted by the severity level of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of non-serious adverse events of the same severity were only counted once per severity category.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03 Grade 1	38 Participants
Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03 Grade 2	34 Participants
Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03 Grade 3	12 Participants
Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03 Grade 4	1 Participants
Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03 Grade 5	0 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with docetaxel, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Urinary tract infection	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Liver function test abnormal	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Any Non-Serious AEs Related to Docetaxel	30 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Diarrhoea	12 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Anaemia	7 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Stomatitis	6 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Leukopenia	4 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Alopecia	4 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Vomiting	4 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Pain	4 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Fatigue	4 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Oedema peripheral	3 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Skin ulcer	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Hypokalaemia	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Lacrimation increased	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Asthenia	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Pyrexia	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Paraesthesia	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Peripheral sensory neuropathy	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Dry skin	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Rash	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Skin exfoliation	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Muscular weakness	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Febrile neutropenia	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Thrombocytopenia	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Sinus tachycardia	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Abdominal pain	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Anal fistula	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Anorectal discomfort	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Constipation	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Frequent bowel movements	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Gastritis	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Haemorrhoidal haemorrhage	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Hyperchlorhydria	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Oral discomfort	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Chest pain	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Peripheral swelling	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Genital herpes	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Pyoderma	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Skin infection	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Decreased appetite	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Hypomagnesaemia	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Hypophosphataemia	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Joint swelling	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Limb discomfort	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Pain in extremity	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Burning sensation	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Neuropathy peripheral	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Productive cough	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Dermatitis acneiform	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Rash maculo-papular	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Seborrhoeic dermatitis	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Skin hypertrophy	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Docetaxel Stevens-Johnson syndrome	1 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with pertuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Rash	3 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Lacrimation increased	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Any Non-Serious AEs Related to Pertuzumab	20 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Diarrhoea	10 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Stomatitis	5 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Pain	3 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Ejection fraction decreased	3 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Chills	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Nasal dryness	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Dry skin	2 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Oedema peripheral	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Skin ulcer	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Left ventricular dysfunction	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Sinus tachycardia	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Abdominal discomfort	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Generalised oedema	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Pyrexia	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Hypokalaemia	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Hypomagnesaemia	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Myalgia	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Burning sensation	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Neuropathy peripheral	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Breast discomfort	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Productive cough	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Dermatitis acneiform	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Onycholysis	1 Participants
Number of Participants With Non-Serious Adverse Events Related to Pertuzumab Rash maculo-papular	1 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with trastuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Non-Serious Adverse Events Related to Trastuzumab	0 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population; the number analyzed represents participants with at least one non-serious adverse event (denominator).

The number of participants with non-serious adverse events was counted by the type of action taken with docetaxel and/or trastuzumab in response to the adverse event in the three following categories: no adjustment, dosage modified/interrupted, and discontinued. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Number of Participants With Non-Serious Adverse Events by Chemotherapy Adjustment With Docetaxel and/or Trastuzumab No Adjustment	45 Participants
Overall Number of Participants With Non-Serious Adverse Events by Chemotherapy Adjustment With Docetaxel and/or Trastuzumab Dosage Modified / Interrupted	9 Participants
Overall Number of Participants With Non-Serious Adverse Events by Chemotherapy Adjustment With Docetaxel and/or Trastuzumab Discontinued	7 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population; the number analyzed represents participants with at least one non-serious adverse event (denominator).

The number of participants with non-serious adverse events was counted by the type of action taken with pertuzumab in response to the adverse event in the three following categories: no action taken, infusion slow down, infusion interrupted, and appropriate medical therapies administered. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Number of Participants With Non-Serious Adverse Events by Action Taken With Pertuzumab No Action Taken	47 Participants
Overall Number of Participants With Non-Serious Adverse Events by Action Taken With Pertuzumab Infusion Slow Down	0 Participants
Overall Number of Participants With Non-Serious Adverse Events by Action Taken With Pertuzumab Infusion Interrupted	0 Participants
Overall Number of Participants With Non-Serious Adverse Events by Action Taken With Pertuzumab Appropriate Medical Therapies Administered	0 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population; the number analyzed represents participants with at least one non-serious adverse event (denominator).

The number of participants with non-serious adverse events was counted by the event outcome in the four following categories: resolved with no sequelae, resolved with sequelae, unresolved, or death. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events with the same outcome were only counted once per category.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Number of Participants With Non-Serious Adverse Events by Event Outcome Resolved with No Sequelae	42 Participants
Overall Number of Participants With Non-Serious Adverse Events by Event Outcome Unresolved	27 Participants
Overall Number of Participants With Non-Serious Adverse Events by Event Outcome Resolved with Sequelae	12 Participants
Overall Number of Participants With Non-Serious Adverse Events by Event Outcome Death	2 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with non-serious adverse events was counted according to whether the event was considered a treatment emergent adverse event (TEAE), which is defined as an adverse event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. Participants with multiple occurrences of non-serious adverse events were only counted once per category.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Number of Participants With Non-Serious Adverse Events by Treatment Emergence (TEAE Versus Non-TEAE) TEAEs	47 Participants
Overall Number of Participants With Non-Serious Adverse Events by Treatment Emergence (TEAE Versus Non-TEAE) Non-TEAEs	3 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with hematological laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events Febrile neutropenia	1 Participants
Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events Anaemia	8 Participants
Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events Leukopenia	4 Participants
Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events Neutropenia	2 Participants
Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events Iron deficiency	1 Participants
Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events Thrombocytopenia	1 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with serum chemistry laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events Hypomagnesaemia	4 Participants
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events Hypokalaemia	2 Participants
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events Hypoalbuminaemia	1 Participants
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events Hypophosphataemia	1 Participants
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events Hyperglycaemia	1 Participants
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events Hyperuricaemia	1 Participants
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events Liver function test abnormal	1 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with coagulation laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events Thrombocytopenia	1 Participants
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events Anal haemorrhage	1 Participants
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events Haemorrhoidal haemorrhage	1 Participants
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events Rectal haemorrhage	1 Participants
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events Upper gastrointestinal haemorrhage	1 Participants
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events Vaginal haemorrhage	1 Participants
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events Thrombophlebitis	1 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Congestive Heart Failure	0 Participants

PRIMARY outcome

Timeframe: Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)

Population: Safety Population

Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF of ≥50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 9	-0.2 percentage points of LVEF Standard Deviation 4.43
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 6	-0.8 percentage points of LVEF Standard Deviation 4.09
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 15	-0.8 percentage points of LVEF Standard Deviation 4.33
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 45	0.0 percentage points of LVEF Standard Deviation 1.41
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Safety Follow-Up	-4.3 percentage points of LVEF Standard Deviation 12.98
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at 6 Month Follow-Up	-1.8 percentage points of LVEF Standard Deviation 4.41
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at 18 Month Follow-Up	-10.0 percentage points of LVEF Standard Deviation 7.07
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Baseline (BL) - Value at Visit	59.6 percentage points of LVEF Standard Deviation 3.92
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 3	-0.7 percentage points of LVEF Standard Deviation 2.95
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 12	0.2 percentage points of LVEF Standard Deviation 3.99
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 18	-1.3 percentage points of LVEF Standard Deviation 4.07
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 21	-1.8 percentage points of LVEF Standard Deviation 5.72
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 24	-0.7 percentage points of LVEF Standard Deviation 4.03
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 27	0.0 percentage points of LVEF Standard Deviation 2.83
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 30	-1.3 percentage points of LVEF Standard Deviation 6.55
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 33	-0.5 percentage points of LVEF Standard Deviation 3.21
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 36	0.0 percentage points of LVEF Standard Deviation 2.90
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 39	-1.3 percentage points of LVEF Standard Deviation 3.51
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 42	1.0 percentage points of LVEF Standard Deviation 0
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 48	-2.0 percentage points of LVEF Standard Deviation 2.83
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at Cycle 51	-18.0 percentage points of LVEF Standard Deviation NA Standard deviation could not be calculated for a value from a single participant.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at 3 Month Follow-Up	-2.1 percentage points of LVEF Standard Deviation 4.80
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at 9 Month Follow-Up	-3.4 percentage points of LVEF Standard Deviation 6.44
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at 12 Month Follow-Up	-2.3 percentage points of LVEF Standard Deviation 4.40
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at 15 Month Follow-Up	-4.7 percentage points of LVEF Standard Deviation 5.51
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at 21 Month Follow-Up	-5.0 percentage points of LVEF Standard Deviation NA Standard deviation could not be calculated for a value from a single participant.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time Change from BL at 24 Month Follow-Up	-5.0 percentage points of LVEF Standard Deviation NA Standard deviation could not be calculated for a value from a single participant.

PRIMARY outcome

Timeframe: Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)

Population: Safety Population

Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF greater than or equal to (≥)50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution. The following are definitions for the three categories of LVEF findings: 'Normal' was defined as LVEF ≥45%; 'Abnormal but not clinically significant' was defined as LVEF <45% but not clinically significant in the investigator's judgment; 'Abnormal and clinically significant' was defined as LVEF <45% and clinically significant in the investigator's judgment.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 18 · Abnormal But Not Clinically Significant	2 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 24 · Normal	8 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 24 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Safety Follow-Up · Abnormal But Not Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 9 Month Follow-Up · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Baseline · Normal	50 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Baseline · Abnormal But Not Clinically Significant	2 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Baseline · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 3 · Normal	48 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 3 · Abnormal But Not Clinically Significant	3 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 3 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 6 · Normal	37 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 6 · Abnormal But Not Clinically Significant	3 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 6 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 9 · Normal	24 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 9 · Abnormal But Not Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 9 · Abnormal and Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 12 · Normal	17 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 12 · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 12 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 15 · Normal	16 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 15 · Abnormal But Not Clinically Significant	2 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 15 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 18 · Normal	11 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 18 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 21 · Normal	10 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 21 · Abnormal But Not Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 21 · Abnormal and Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 24 · Abnormal But Not Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 27 · Normal	5 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 27 · Abnormal But Not Clinically Significant	2 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 27 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 30 · Normal	3 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 30 · Abnormal But Not Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 30 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 33 · Normal	5 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 33 · Abnormal But Not Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 33 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 36 · Normal	5 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 36 · Abnormal But Not Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 36 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 39 · Normal	2 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 39 · Abnormal But Not Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 39 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 42 · Normal	2 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 42 · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 42 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 45 · Normal	2 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 45 · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 45 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 48 · Normal	2 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 48 · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 48 · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 51 · Normal	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 51 · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Cycle 51 · Abnormal and Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Safety Follow-Up · Normal	24 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time Safety Follow-Up · Abnormal and Clinically Significant	3 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 3 Month Follow-Up · Normal	17 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 3 Month Follow-Up · Abnormal But Not Clinically Significant	3 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 3 Month Follow-Up · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 6 Month Follow-Up · Normal	18 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 6 Month Follow-Up · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 6 Month Follow-Up · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 9 Month Follow-Up · Normal	13 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 9 Month Follow-Up · Abnormal and Clinically Significant	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 12 Month Follow-Up · Normal	10 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 12 Month Follow-Up · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 12 Month Follow-Up · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 15 Month Follow-Up · Normal	3 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 15 Month Follow-Up · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 15 Month Follow-Up · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 18 Month Follow-Up · Normal	2 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 18 Month Follow-Up · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 18 Month Follow-Up · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 21 Month Follow-Up · Normal	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 21 Month Follow-Up · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 21 Month Follow-Up · Abnormal and Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 24 Month Follow-Up · Normal	1 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 24 Month Follow-Up · Abnormal But Not Clinically Significant	0 Participants
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time 24 Month Follow-Up · Abnormal and Clinically Significant	0 Participants

PRIMARY outcome

Timeframe: From Baseline until end of study (up to approximately 3 years)

Population: Safety Population

The number of participants with any adverse event (serious or non-serious) that led to treatment discontinuation during the study was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one adverse event that led to treatment discontinuation may have been reported per participant.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Adverse Events Leading to Treatment Discontinuation Any AEs Leading to Treatment Discontinuation	16 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Disease progression	5 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Ejection fraction decreased	3 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Headache	2 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Anaemia	1 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Death	1 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Diarrhoea	1 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Dyspnoea	1 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Febrile neutropenia	1 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Infusion related reaction	1 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Sepsis	1 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Septic shock	1 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Shock	1 Participants
Number of Participants With Adverse Events Leading to Treatment Discontinuation Stevens-Johnson syndrome	1 Participants

SECONDARY outcome

Timeframe: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)

Population: ITT Population

The overall response rate (ORR) was defined as the percentage of participants with best overall response of Complete Response (CR) or Partial Response (PR), confirmed by repeat assessment no less than 4 weeks after the response criteria were first met, using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Participants who either had not achieved CR or PR or were without a post-baseline tumor assessment were to be considered non-responders. All measurable and non-measurable lesions were documented at screening and re-assessed at each subsequent tumor evaluation. Response was assessed by the investigator on the basis of physical examinations, computed tomography (CT) scans, and magnetic resonance imaging (MRI). The same radiographic procedure was used throughout the study, and assessments were preferably performed by the same evaluator. The 95% confidence intervals were calculated using Clopper-Pearson methodology.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Overall Response Rate Responders (ORR)	82.7 percentage of participants Interval 69.67 to 91.77
Overall Response Rate Non-Responders	17.3 percentage of participants Interval 8.23 to 30.33

SECONDARY outcome

Timeframe: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)

Population: ITT Population

The best overall response was defined as the best response, out of all the documented responses over the course of the entire study period, using RECIST v1.1. All measurable and non-measurable lesions were documented at screening and re-assessed at each subsequent tumor evaluation. Response was assessed by the investigator on the basis of physical examinations, computed tomography (CT) scans, and magnetic resonance imaging (MRI). The same radiographic procedure was used throughout the study, and assessments were preferably performed by the same evaluator.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants by Best Overall Response Complete Response (CR)	0 Participants
Number of Participants by Best Overall Response Partial Response (PR)	43 Participants
Number of Participants by Best Overall Response Progressive Disease (PD)	1 Participants
Number of Participants by Best Overall Response Stable Disease (SD)	6 Participants
Number of Participants by Best Overall Response Unable to Assess	2 Participants

SECONDARY outcome

Timeframe: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)

Population: ITT Population

Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed or died or were lost to follow up at the time of the analysis were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants With Disease Progression or Death or Who Were Censored for Progression-Free Survival Analysis Disease Progression or Death	32 Participants
Number of Participants With Disease Progression or Death or Who Were Censored for Progression-Free Survival Analysis Censored	20 Participants

SECONDARY outcome

Timeframe: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)

Population: ITT Population

Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed or died, or were lost to follow up at the time of the analysis, were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Median Duration of Progression-Free Survival	23.0 months Interval 13.0 to 29.0

SECONDARY outcome

Timeframe: Months 2, 3, 5, 6, 7, 8, 9, 11, 13, 15, 16, 17, 18, 19, 23, 24, 25, 27, 29, and 32

Population: ITT Population

Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed, died or were lost to follow up at the time of the analysis were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 6 Months	88.30 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 2 Months	98.08 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 3 Months	96.15 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 5 Months	90.27 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 7 Months	82.42 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 8 Months	78.49 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 9 Months	74.57 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 11 Months	68.52 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 13 Months	64.49 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 15 Months	60.33 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 16 Months	58.10 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 17 Months	55.86 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 18 Months	53.63 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 19 Months	51.30 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 23 Months	48.96 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 24 Months	46.63 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 25 Months	41.72 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 27 Months	36.16 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 29 Months	32.87 Percent probability of PFS
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months At 32 Months	29.59 Percent probability of PFS

SECONDARY outcome

Timeframe: From Baseline up to death from any cause (up to approximately 3 years)

Population: ITT Population

Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Number of Participants Who Died or Were Censored for Overall Survival Analysis Death	15 Participants
Number of Participants Who Died or Were Censored for Overall Survival Analysis Censored	37 Participants

SECONDARY outcome

Timeframe: From Baseline up to death from any cause (up to approximately 3 years)

Population: ITT Population

Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Median Duration of Overall Survival	NA months Interval 26.0 to The median and the upper limit of the inter-quartile range of OS duration were not estimable because they were not reached at the time of analysis.

SECONDARY outcome

Timeframe: Months 3, 9, 13, 14, 15, 18, 19, 20, 24, 25, 27, 32, 33, and 34

Population: ITT Population

Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method.

Outcome measures

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 Participants Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 3 Months	96.15 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 9 Months	88.30 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 13 Months	88.30 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 14 Months	88.30 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 15 Months	88.30 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 18 Months	83.66 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 19 Months	83.66 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 20 Months	83.66 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 24 Months	81.12 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 25 Months	81.12 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 27 Months	68.14 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 32 Months	68.14 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 33 Months	64.36 Percent probability of OS
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months At 34 Months	64.36 Percent probability of OS

Adverse Events

Pertuzumab in Combination With Trastuzumab and Docetaxel

Serious events: 31 serious events

Other events: 47 other events

Deaths: 15 deaths

Serious adverse events

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 participants at risk Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Blood and lymphatic system disorders Febrile neutropenia	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Cardiac disorders Left ventricular dysfunction	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Diarrhoea	9.6% 5/52 • Number of events 5 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Death	5.8% 3/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Disease progression	11.5% 6/52 • Number of events 6 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Fatigue	5.8% 3/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Multiple organ dysfunction syndrome	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Septic shock	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Investigations Ejection fraction decreased	5.8% 3/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.8% 3/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Salivary hypersecretion	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Cardiac disorders Sinus tachycardia	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Gastroenteritis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Enteritis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Abdominal pain	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Rash	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Vascular disorders Shock	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Device related sepsis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Injury, poisoning and procedural complications Infusion related reaction	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Vomiting	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Stomatitis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Pyrexia	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Congenital, familial and genetic disorders Congenital arterial malformation	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Haematemesis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Osteomyelitis salmonella	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Sepsis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Injury, poisoning and procedural complications Clavicle fracture	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Injury, poisoning and procedural complications Spinal fracture	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Metabolism and nutrition disorders Decreased appetite	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Nervous system disorders Dizziness	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Nervous system disorders Seizure	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Product Issues Device dislocation	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.

Other adverse events

Measure	Pertuzumab in Combination With Trastuzumab and Docetaxel n=52 participants at risk Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Gastrointestinal disorders Diarrhoea	32.7% 17/52 • Number of events 43 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Stomatitis	15.4% 8/52 • Number of events 13 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Blood and lymphatic system disorders Anaemia	15.4% 8/52 • Number of events 11 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Pyrexia	15.4% 8/52 • Number of events 10 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Blood and lymphatic system disorders Leukopenia	7.7% 4/52 • Number of events 6 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Vascular disorders Lymphoedema	7.7% 4/52 • Number of events 5 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Rash	9.6% 5/52 • Number of events 5 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Myalgia	9.6% 5/52 • Number of events 5 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Metabolism and nutrition disorders Hypomagnesaemia	7.7% 4/52 • Number of events 7 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Back pain	13.5% 7/52 • Number of events 8 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Arthralgia	9.6% 5/52 • Number of events 7 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Vomiting	11.5% 6/52 • Number of events 7 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Pain	9.6% 5/52 • Number of events 7 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Nasopharyngitis	9.6% 5/52 • Number of events 7 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Oedema peripheral	7.7% 4/52 • Number of events 7 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Alopecia	7.7% 4/52 • Number of events 6 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Eye disorders Lacrimation increased	9.6% 5/52 • Number of events 6 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Nervous system disorders Headache	11.5% 6/52 • Number of events 7 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Respiratory, thoracic and mediastinal disorders Cough	13.5% 7/52 • Number of events 11 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Pain in extremity	15.4% 8/52 • Number of events 13 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Nervous system disorders Dizziness	11.5% 6/52 • Number of events 7 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Fatigue	15.4% 8/52 • Number of events 8 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Asthenia	7.7% 4/52 • Number of events 4 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Abdominal pain	5.8% 3/52 • Number of events 4 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Chills	7.7% 4/52 • Number of events 4 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Peripheral swelling	5.8% 3/52 • Number of events 4 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Viral infection	5.8% 3/52 • Number of events 4 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Investigations Ejection fraction decreased	5.8% 3/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Metabolism and nutrition disorders Decreased appetite	7.7% 4/52 • Number of events 4 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Bone pain	5.8% 3/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Nervous system disorders Paraesthesia	5.8% 3/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Psychiatric disorders Insomnia	7.7% 4/52 • Number of events 4 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.8% 3/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.8% 3/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Dry skin	5.8% 3/52 • Number of events 4 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Pruritus generalised	5.8% 3/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Blood and lymphatic system disorders Febrile neutropenia	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Blood and lymphatic system disorders Neutropenia	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Blood and lymphatic system disorders Thrombocytopenia	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Cardiac disorders Left ventricular dysfunction	3.8% 2/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Cardiac disorders Pericardial effusion	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Cardiac disorders Sinus tachycardia	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Ear and labyrinth disorders Ear pain	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Abdominal discomfort	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Abdominal pain upper	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Anal fissure	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Anal fistula	1.9% 1/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Anal haemorrhage	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Anal inflammation	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Anorectal discomfort	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Constipation	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Dry mouth	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Frequent bowel movements	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Gastric ulcer	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Gastritis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Gingival swelling	1.9% 1/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Haemorrhoidal haemorrhage	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Hyperchlorhydria	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Nausea	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Oral discomfort	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Rectal haemorrhage	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Gastrointestinal disorders Toothache	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Chest pain	3.8% 2/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Disease progression	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Generalised oedema	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
General disorders Non-cardiac chest pain	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Acute sinusitis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Carbuncle	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Cellulitis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Fungal skin infection	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Furuncle	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Genital herpes	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Herpes zoster	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Hordeolum	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Lymph gland infection	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Pyoderma	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Respiratory tract infection	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Rhinitis	1.9% 1/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Skin infection	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Infections and infestations Urinary tract infection	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Eye disorders Meibomianitis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Eye disorders Ocular hyperaemia	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Injury, poisoning and procedural complications Breast procedural complication	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Injury, poisoning and procedural complications Incision site pain	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Injury, poisoning and procedural complications Infusion related reaction	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Injury, poisoning and procedural complications Procedural site reaction	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Investigations Liver function test abnormal	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Joint swelling	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Limb discomfort	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Muscular weakness	1.9% 1/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	1.9% 1/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Infected neoplasm	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Nervous system disorders Burning sensation	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Nervous system disorders Neuropathy peripheral	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Nervous system disorders Peripheral sensory neuropathy	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Nervous system disorders Speech disorder developmental	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Reproductive system and breast disorders Breast discomfort	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Reproductive system and breast disorders Vaginal haemorrhage	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Respiratory, thoracic and mediastinal disorders Nasal dryness	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Respiratory, thoracic and mediastinal disorders Productive cough	3.8% 2/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Respiratory, thoracic and mediastinal disorders Rales	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Respiratory, thoracic and mediastinal disorders Wheezing	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Dermatitis acneiform	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Lichen planus	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Onycholysis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Pain of skin	1.9% 1/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Pruritus	1.9% 1/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Rash maculo-papular	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Scar pain	1.9% 1/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Skin discolouration	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Skin exfoliation	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	3.8% 2/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Skin hypertrophy	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Skin ulcer	3.8% 2/52 • Number of events 4 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Vascular disorders Hypertension	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Vascular disorders Thrombophlebitis	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Metabolism and nutrition disorders Hyperglycaemia	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Metabolism and nutrition disorders Hyperuricaemia	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Metabolism and nutrition disorders Hypoalbuminaemia	1.9% 1/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Metabolism and nutrition disorders Hypokalaemia	3.8% 2/52 • Number of events 3 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Metabolism and nutrition disorders Hypophosphataemia	1.9% 1/52 • Number of events 2 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Metabolism and nutrition disorders Iron deficiency	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.
Metabolism and nutrition disorders Vitamin B12 deficiency	1.9% 1/52 • Number of events 1 • From Baseline until end of study (up to 3 years) After informed consent, and prior to dosing, serious adverse events (SAEs) considered related to a study mandated procedure were reportable. As of cycle 1 all adverse events and SAEs were monitored continuously and collected until the end-of-study visit.

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