A Study to Evaluate Patient Preference for Home Administr... | NCT05415215

ID	Type	Description	Link
2021-002346-33	EudraCT Number
2023-506380-33-00	EU Trial (CTIS) Number

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A: Pertuzumab IV and Trastuzumab IV Plus Investigator's Choice of Chemotherapy	Other	During the neoadjuvant phase, the enrolled participants randomized to this arm will receive treatment with pertuzumab and trastuzumab intravenously (PH IV) plus investigator's choice of chemotherapy (Option 1, 2, or 3). With chemotherapy Option 1, PH IV will be administered at each cycle from Cycles 1 to 6 (1 cycle is 3 weeks); with chemotherapy Options 2 and 3, PH IV will be administered once per cycle from Cycles 5 to 8 (1 cycle is 3 weeks).	Drug: Pertuzumab IV Drug: Trastuzumab IV Drug: Investigator's Choice of Chemotherapy Procedure: Surgery Radiation: Radiotherapy
Arm B: PH FDC SC Plus Investigator's Choice of Chemotherapy	Other	During the neoadjuvant phase, the enrolled participants randomized to this arm will receive treatment with the fixed dose combination of pertuzumab and trastuzumab for subcutaneous use (PH FDC SC) plus investigator's choice of chemotherapy (Option 1, 2, or 3). With chemotherapy Option 1, PH FDC SC will be administered at each cycle from Cycles 1 to 6 (1 cycle is 3 weeks); with chemotherapy Options 2 and 3, PH FDC SC will be administered once per cycle from Cycles 5 to 8 (1 cycle is 3 weeks).	Drug: Fixed Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Use (PH FDC SC) Drug: Investigator's Choice of Chemotherapy Procedure: Surgery Radiation: Radiotherapy
Arm C: Adjuvant PH FDC SC in Hospital, Then at Home	Experimental	During the adjuvant phase, participants who have achieved pCR after surgery will be treated with 2 cycles of PH FDC SC in the hospital (run-in period). After completion of the last cycle of radiotherapy and the last cycle of PH FDC SC (run-in period), participants will then be randomized with a ratio of 1:1 into one of two treatment arms (Arm C or D) in a cross-over treatment period to receive the next 6 cycles of PH FDC SC treatment. Participants in Arm C will receive 3 cycles of PH FDC SC in the hospital and then 3 cycles of PH FDC SC in the home setting. After the cross-over treatment period, participants will receive the remaining PH FDC SC treatment cycles required to complete the planned 18 cycles of HER2-directed therapy, unless of disease recurrence, unacceptable toxicity, or withdrawal. Study treatment during this treatment continuation period will be administered either in the hospital or in the home setting as selected by the participant at the end of the crossover period.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Fixed Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Use (PH FDC SC)	Drug	PH FDC SC is administered subcutaneously (SC) as a fixed non-weight-based dose. A loading dose of 1200 milligram (mg) pertuzumab, 600 mg trastuzumab, and 30,000 units of recombinant human PH20 hyaluronidase (rHuPH20) is given in the first cycle (1 cycle is 21 days). In subsequent cycles, maintenance doses of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units rHuPH20 are administered once every 3 weeks (Q3W).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cross-over Period: Percentage of Participants Who Preferred the Administration of PH FDC SC in the Home Setting Compared With the Hospital Setting in Question 1 of the Patient Preference Questionnaire (PPQ)	The PPQ was used to evaluate the participant preference for PH FDC SC compared to P+H IV. Participants completed the PPQ, where Question (Q) 1 was: "All things considered, which setting for your treatment did you prefer?" Participants were required to select one of the following options: home, hospital or no preference. The reported results show the percentage of participants who preferred receiving PH FDC SC at home setting over the hospital setting. Percentages were rounded off.	Upon completion of adjuvant cross-over period (Day 1 of Cycle 8 or 9; Cycle length = 21 days)

Secondary Outcomes

Measure	Description	Time Frame
Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 1a of HCPQ - Drug Preparation Area	HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with preparation of P+H IV and/or administration of PH FDC SC completed the following question of the HCPQ: Q1a: "Please indicate which treatment preparation the estimates relate to". HCPs were required to select one of the following options: PH FDC SC or P+H IV. The response to Q1a was used to further assess Q1b: How long did it take to prepare the treatment for use? Percentages were rounded off.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Intact skin at planned site of subcutaneous (SC) injections
Left ventricular ejection fraction (LVEF) greater than or equal to (≥)55% by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
Negative human immunodeficiency virus (HIV) test at screening
Negative hepatitis B surface antigen (HBsAg) test at screening
Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: Negative total hepatitis B core antibody (HBcAb); Positive total HBcAb test followed by a negative (per local laboratory definition) hepatitis B virus (HBV) DNA test
Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
For female participants of childbearing potential: agreement to remain abstinent or use contraception and agree to refrain from donating eggs during the treatment period and for 7 months after the final dose of the study treatment
For male participants: agreement to remain abstinent or use a condom, and agree to refrain from donating sperm during the treatment period and for 7 months after the final dose of study treatment

Disease-specific Inclusion Criteria:

Female and male participants with stage II-IIIC early or locally advanced/inflammatory human epidermal growth factor receptor 2-positive (HER2+) breast cancer
Primary tumor >2 centimetres (cm) in diameter, or node-positive disease
HER2+ breast cancer confirmed by a local laboratory prior to study enrollment. HER2+ status will be determined based on pretreatment breast biopsy material and defined as 3+ by Immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) following American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines 2018 and updates (Wolff et al. Arch Pathol Lab Med 2018)
Hormone receptor status of the primary tumor determined by local assessment following American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and updates (Allison et al. J Clin Oncol 2020)
Agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy, including the axillary nodes
Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for local confirmation of HER2 and hormone receptor status following current ASCO/CAP guidelines

Inclusion Criteria for Treatment with Adjuvant PH FDC SC:

Completed the neoadjuvant phase of this study and underwent surgery, and achieved pathologic complete response (pCR), defined as eradication of invasive disease in the breast and axilla according to the current American Joint Committee on Cancer (AJCC) staging system classification, and using the resected specimen by the local pathologist on the basis of guidelines to be provided in a pathology manual
Adequate wound healing after breast cancer surgery per investigator's assessment to allow initiation of study treatment within less than or equal to (≤)9 weeks of last systemic neoadjuvant therapy

Exclusion Criteria:

Stage IV (metastatic) breast cancer
History of concurrent or previously treated non-breast malignancies, except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin. A participant with previous invasive non-breast cancer is eligible provided he/she has been disease free for more than 5 years
Participants who are pregnant or breastfeeding or intending to become pregnant during the study or within 7 months after the final dose of study treatments
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Active, unresolved infections at screening requiring treatment
Participants who may have had a recent episode of thromboembolism and are still trying to optimize the anticoagulation dose and/or have not normalized their International Normalized Ratio (INR)
Serious cardiac illness or medical conditions
History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
Inadequate bone marrow function
Impaired liver function
Renal function with creatinine clearance <50 mL/min using the Cockroft-Gault formula and serum creatinine >1.5x upper limit of normal (ULN)
Major surgical procedure unrelated to breast cancer within 28 days prior to study entry or anticipation of the need for major surgery during the course of study treatment
Current severe, uncontrolled systemic disease that may interfere with planned treatment
Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
Treatment with a live vaccine (e.g., FluMist) in the 30 days prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment or within 90 days after the final dose of study treatment
Known active liver disease, for example, active viral hepatitis infection, autoimmune hepatic disorders, or sclerosing cholangitis
Known hypersensitivity to any of the study drugs, excipients, and/or murine proteins or a history of severe allergic or immunological reactions, e.g., difficult to control asthma
Current chronic daily treatment with corticosteroids
Assessment by the investigator as being unable or unwilling to comply with the requirements of the protocol

Cancer-specific Exclusion Criteria for Neoadjuvant Phase:

Participants who have received any previous systemic therapy for treatment or prevention of breast cancer, or previous chest irradiation for the treatment of cancer
Participants who have a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment or radiation therapy to the ipsi- or contralateral breast cancer
Participants with high-risk for breast cancer who have received chemopreventive drugs in the past
Participants with multicentric breast cancer, unless all tumors are HER2+
Participants with bilateral breast cancer
Participants who have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes
Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy
Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy

Exclusion Criterion for Treatment with Adjuvant Trastuzumab Emtansine (Arm E):

Current Grade ≥3 peripheral neuropathy (according to the NCI CTCAE v5.0)

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Centro de Investigaciones Médicas y Desarrollo LC S.R.L		Buenos Aires	Ciudad Autónoma de BuenosAires	C1113AAE	Argentina

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 25, 2024	Nov 19, 2025

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cross-over Period: Percentage of Participants Who Preferred the Administration of PH FDC SC in the Home Setting Compared With the Hospital Setting in Question 1 of the Patient Preference Questionnaire (PPQ)

The PPQ was used to evaluate the participant preference for PH FDC SC compared to P+H IV. Participants completed the PPQ, where Question (Q) 1 was: "All things considered, which setting for your treatment did you prefer?" Participants were required to select one of the following options: home, hospital or no preference. The reported results show the percentage of participants who preferred receiving PH FDC SC at home setting over the hospital setting. Percentages were rounded off.

Adjuvant cross-over modified intent-to-treat (mITTcross) population included all randomized participants assigned into the cross-over period who received at least one dose of PH FDC SC, completed Question 1 of the PPQ, and completed radiotherapy before entering the cross-over period.

Posted

Number

percentage of participants

Upon completion of adjuvant cross-over period (Day 1 of Cycle 8 or 9; Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home	Participants who completed the run-in period and were randomized to Arm C received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the hospital setting, followed by 3 cycles in the home setting (Cycle length = 21 days).
OG001	Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital	Participants who completed the run-in period and were randomized to Arm D received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the home setting, followed by 3 cycles in the hospital setting (Cycle length = 21 days).

Units	Counts
Participants	OG00087 OG00183

Title

Denominators

Categories

Home

Title	Measurements
	OG00069.0 OG00159.0

Hospital

Title	Measurements
	OG000

Secondary

Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 1a of HCPQ - Drug Preparation Area

HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with preparation of P+H IV and/or administration of PH FDC SC completed the following question of the HCPQ: Q1a: "Please indicate which treatment preparation the estimates relate to". HCPs were required to select one of the following options: PH FDC SC or P+H IV. The response to Q1a was used to further assess Q1b: How long did it take to prepare the treatment for use? Percentages were rounded off.

Participants could have changed from P+H IV treatment to PH FDC SC treatment, in exceptional circumstances and at the investigator discretion. Overall number analyzed is the number of HCPs who answered Q1a of the HCPQ. Number analyzed is the number of HCPs who answered Q1a of the HCPQ at the specified time point.

Posted

Number

percentage of HCPs

Day 1 of Cycles 1-8 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).
OG001	Arm B, Neoadjuvant Phase: PH FDC SC

Secondary

Neoadjuvant Phase: Duration of Treatment Preparation, According to Healthcare Professionals' Responses to Question 1b of HCPQ - Drug Preparation Area

HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with preparation of P+H IV and/or administration of PH FDC SC completed the following question of the HCPQ: Q1b: "How long did it take to prepare the treatment for use?" This was a follow up question to Q1a: "Please indicate which treatment preparation the estimates relate to" for which HCPs were required to select one of the following options: PH FDC SC or P+H IV.

Overall number analyzed is the number of HCPs who answered Q1b of the HCPQ. Number analyzed is the number of HCPs who answered Q1b of the HCPQ at the specified time point.

Posted

Median

Full Range

minutes

Day 1 of Cycles 1-8 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).
OG001	Arm B, Neoadjuvant Phase: PH FDC SC	Participants received a loading dose of pertuzumab, 1200 mg, trastuzumab, 600 mg, and recombinant human PH20 hyaluronidase (rHuPH20), 30,000 units (U), as a SC injection on Day 1 of Cycle 1 (Cycle length = 21 days) followed by maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg and rHuPH20, 20,000 U, as a SC injection, Q3W along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Secondary

Neoadjuvant Phase: Percentage of HCPs by Their Response to Question 2 of the HCPQ - Drug Preparation Area

HCP=any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with preparation of P+H IV and/or administration of PH FDC SC completed the following question 2 of the HCPQs: In your opinion, if all P+H IV infusions were switched to PH FDC SC injections, please indicate how strongly you agree/disagree with each of the following statements. 2a: Staff will have increased availability for other tasks in the pharmacy. 2b: Administrative procedures related to PH FDC SC require less time. 2c: Using PH FDC SC provides more flexibility for pharmacy staff in managing their workload. 2d: As PH FDC SC is fixed-dose, potential dosing errors are avoided. 2e: As PH FDC SC is fixed-dose, there is less drug wastage. 2f: Less storage space for PH FDC SC-related supplies is required in the pharmacy, as there is no need for reconstitution. 2g: Number of preparation steps & staff time commitment are reduced. Percentages were rounded off.

Overall number analyzed is the number of HCPs who answered Q2 of the HCPQ. Number analyzed is the number of HCPs who responded to each sub-question of Q2 (Q2a-Q2g) of the HCPQ.

Posted

Number

percentage of HCPs

Up to Day 1 of Cycle 8 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Secondary

Neoadjuvant Phase: Percentage of HCPs by Their Responses to Questions 1a-1e of the HCPQ - Administering Treatment

HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with administration of P+H IV and/or PH FDC SC completed the following Questions of the HCPQ: Q1a: Please indicate which treatment preparation the estimates relate to. Q1b: Did the participant have existing IV access? Q1c: If new IV access was needed for this cycle of treatment, please indicate what type of IV access was provided. Q1d: What type of existing IV access did the participant have? Q1e: When did the existing IV access place? Percentages were rounded off.

PICC = peripherally inserted central catheter.

Participants could have changed from P+H IV treatment to PH FDC SC treatment, in exceptional circumstances and at the investigator discretion. Overall number analyzed is the number of HCPs who answered Q1a to Q1e of the HCPQ. Number analyzed is the number of HCPs who answered Q1a to Q1e of the HCPQ at the specified time point.

Posted

Number

percentage of HCPs

Day 1 of Cycles 1-8 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Secondary

Neoadjuvant Phase: Duration of Treatment Administration According to HCPs' Responses to Questions 1c (Sub-part), 1f, and 1g of the HCPQ - Administering Treatment

HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with administration of P+H IV and/or PH FDC SC completed the following Questions of the HCPQ: Q1c: If new IV access was needed for this cycle of treatment, how long (in minutes) this took to set up? Q1f: How long (in minutes) did it take to administer the treatment (P+H IV or PH FDC SC)? Q1g: How long (in minutes) was the participant in the Treatment Area in total? Percentages have been rounded off.

Overall number analyzed is the number of HCPs who answered Q1c, Q1f and Q1g of the HCPQ. Number analyzed is the number of HCPs who answered Q1c, Q1f and Q1g of the HCPQ at the specified time point.

Posted

Median

Full Range

minutes

Day 1 of Cycles 1-8 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).
OG001	Arm B, Neoadjuvant Phase: PH FDC SC

Secondary

Neoadjuvant Phase: Percentage of HCPs by Their Response to Question 2 (2a to 2e) of the HCPQ - Administering Treatment

HCP was defined as any personnel involved in the drug preparation &/or drug administration processes. HCPs who have had experience with administration of P+H IV &/or PH FDC SC completed Q2 (2a-2e) of the HCPQ: In your opinion, if all P+H IV infusions were switched to PH FDC SC injections, please indicate how strongly you agree/disagree with each of the following statements. 2a: Participants may be moved out of the Treatment Area (for infusion treatment) to receive PH FDC SC injections. 2b: PH FDC SC's SC route of administration allows for more flexible treatment scheduling. 2c: Frees up infusion chairs for participants whose treatments can only be given IV. 2d: Waiting list for any P+H IV treatment at the Treatment Area is reduced. 2e: Staff's work burden is reduced, enhancing work performance. The 6 available options were: Strongly Disagree, Disagree, Neutral, Agree, Strongly Agree and Not applicable. Percentages were rounded off.

Overall number analyzed is the number of HCPs who answered any sub part Q2 (2a to 2e) of the HCPQ. Number analyzed is the number of HCPs who answered each sub-question of Q2 (2a to 2e) of the HCPQ.

Posted

Number

percentage of HCPs

Up to Cycle 8 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Secondary

Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 2 (2f to 2j) of the HCPQ - Administering Treatment

HCP was defined as any personnel involved in the drug preparation &/or drug administration processes. HCPs who have had experience with administration of P+H IV &/or PH FDC SC completed Question 2 (2f to 2j) of the HCPQ: In your opinion, if all P+H IV infusions were switched to PH FDC SC injections, please indicate how strongly you agree/disagree with each of the following statements. 2f: More interaction time between HCPs and participants. 2g: Staff have more time for further professional education/development. 2h: Staff has more time for administrative tasks. 2i: Participants on PH FDC SC spend less time in the Treatment Area. 2j: Participants prefer PH FDC SC to P+H IV. The 6 available options were: Strongly Disagree, Disagree, Neutral, Agree, Strongly Agree and Not applicable. Percentages were rounded off.

Overall number analyzed is the number of HCPs who answered any sub part of Q2 (2f to 2j) of the HCPQ. Number analyzed is the number of HCPs who answered each sub-question of Q2 (2f to 2j) of the HCPQ.

Posted

Number

percentage of HCPs

Up to Cycle 8 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Secondary

Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 3 to 11 of the HCPQ - Administering Treatment

HCPs who have had experience with administration of P+H IV &/or PH FDC SC completed Questions 3 to 11 of the HCPQ: Q3: Which was more convenient for the participant? Q4: Which was better for optimising participant care at your institution? Q5: Which required less time to administer (excluding observation period)? Q6: Which required less use of institutional resources (e.g., staff time, facility costs, equipment use)? Q7: Which required less time to administer all the treatment (including IV chemotherapy)? Q8: Which allowed for attending to more participants because of time savings from the mode of administration of pertuzumab and trastuzumab? Q9: During the NP you had to administer IV chemotherapy through participant's IV access. You prefer to accompany IV chemotherapy with? Q10: Which was preferred by participants? Q11: How frequently would you recommend PH FDC SC administration to your participants in the future? Percentages were rounded off.

Overall number analyzed is the number of HCPs who answered any of the questions from Q3 to Q11 of the HCPQ. Number analyzed is the number of HCPs who answered each specific question (Q3 to Q11) of the HCPQ.

Posted

Number

percentage of HCPs

Up to Cycle 8 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Secondary

Percentage of Participants Who Achieved pCR Post-surgery

pCR was defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0), according to the current American Joint Committee on Cancer (AJCC) staging system classification. Percentages were rounded off.

FASab included all randomized participants, regardless of whether they received treatment. Overall number analyzed is the number of participants with data available for analysis.

Posted

Number

percentage of participants

Up to approximately 7.8 months

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).
OG001	Arm B, Neoadjuvant Phase: PH FDC SC	Participants received a loading dose of pertuzumab, 1200 mg, trastuzumab, 600 mg, and recombinant human PH20 hyaluronidase (rHuPH20), 30,000 units (U), as a SC injection on Day 1 of Cycle 1 (Cycle length = 21 days) followed by maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg and rHuPH20, 20,000 U, as a SC injection, Q3W along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Secondary

Neoadjuvant Phase: Change From Baseline in Health-related Quality of Life (HRQoL) Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C30) Scores

EORTC QLQ-C30=cancer-specific instrument consisting of 30 questions that evaluated 5 aspects of participant functioning (physical, emotional, role, cognitive & social), 3 symptom scales (fatigue, nausea & vomiting & pain), global health status/quality of life (GHS/QoL) & 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties). Functioning & symptom items used a 4-point scale, scores ranging from 1=Not at all to 4=Very much. GHS/QoL questions used a 7-point scale, scores ranging from 1=Very poor to 7=Excellent. All EORTC scales & single-item measures were linearly transformed to a score range of 0-100. High score for functional/GHS scale=high/healthy level of functioning/better HRQoL & high score for symptom scale=high level of symptom severity. A positive change from baseline=improvement & negative change=worsening in QoL & functioning scales. A positive change from baseline=deterioration & negative change=improvement in symptom scales.

FASab included all randomized participants, regardless of whether they received treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Day 1 of Cycles 6 and 8 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Secondary

Adjuvant Phase: Change From Baseline in HRQoL Assessed by EORTC QLQ C30 Scores

EORTC QLQ-C30=cancer-specific instrument consisting of 30 questions that evaluated 5 aspects of participant functioning (physical, emotional, role, cognitive & social), 3 symptom scales (fatigue, nausea & vomiting & pain), GHS/QoL & 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties). Functioning & symptom items used a 4-point scale, scores ranging from 1=Not at all to 4=Very much. GHS/QoL questions used a 7-point scale, scores ranging from 1=Very poor to 7=Excellent. All EORTC scales & single-item measures were linearly transformed to a score range of 0-100. High score for functional/GHS scale=high/healthy level of functioning/better HRQoL & high score for symptom scale=high level of symptom severity. A positive change from baseline=improvement & negative change=worsening in QoL & functioning scales. A positive change from baseline=deterioration & negative change=improvement in symptom scales.

mITTcross population included all randomized participants assigned into the cross-over period who received at least one dose of PH FDC SC, completed Question 1 of the PPQ and completed radiotherapy before entering the cross-over period. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Posted

Mean

Standard Deviation

score on a scale

Baseline (Cycle 1) of Run-in Period; Day 1 of Cycles 1, 3, and 6 in the Cross-over Period (Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home

Secondary

Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 1a and 1c of the HCPQ - Drug Preparation Area

HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with preparation and/or administration of PH FDC SC completed the following questions of the HCPQ: Q1a: Where was the treatment prepared? Q1c: Which healthcare professionals were involved in the treatment preparation processes? The 4 available response options for Q1a were: Participant's home, Hospital pharmacy, Day oncology unit, or Other. The 5 available response options for Q1c were: Physician, Nurse, Pharmacist, All of them or Other. Percentages were rounded off.

Overall number analyzed is the number of HCPs who answered Q1a and Q1c of the HCPQ. Number analyzed is the number of HCPs who answered Q1a and Q1c of the HCPQ at the specified timepoint.

Posted

Number

percentage of HCPs

Day 1 of Cycles 3 and 6 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home	Participants who completed the run-in period and were randomized to Arm C received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the hospital setting, followed by 3 cycles in the home setting (Cycle length = 21 days).
OG001	Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital

Secondary

Adjuvant Cross-over Period: Duration of Treatment Preparation, According to HCPs' Responses to Question 1b of the HCPQ - Drug Preparation Area

HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with preparation and/or administration of PH FDC SC completed the following parts of question Q1b: Q1b(1): How long did it take to prepare the treatment for use? Q1b(2): Time from the preparation place to reach the participant's home.

Overall number analyzed is the number of HCPs who answered Q1b of the HCPQ. Number analyzed is the number of HCPs who answered Q1b of the HCPQ at the specified timepoint.

Posted

Median

Full Range

minutes

Day 1 of Cycles 3 and 6 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home	Participants who completed the run-in period and were randomized to Arm C received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the hospital setting, followed by 3 cycles in the home setting (Cycle length = 21 days).
OG001	Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital	Participants who completed the run-in period and were randomized to Arm D received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the home setting, followed by 3 cycles in the hospital setting (Cycle length = 21 days).

Secondary

Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 2, 3 and 4 of the HCPQ - Drug Preparation Area

HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with preparation and/or administration of PH FDC SC completed the questions 2, 3 and 4 of the HCPQ: Q2: If all PH FDC SC injections were switched from an in-hospital setting to the participant´s home, please indicate how strongly you agree or disagree with each of the following statements: 2a: Staff will have increased availability for other tasks in the hospital´s pharmacy. 2b: Administrative procedures related to PH FDC SC will require less time. 2c: Number of preparation steps and staff time commitment are reduced. The 5 response options were: Strongly disagree, Disagree, Neutral, Agree, Strongly agree or Not applicable. Q3: Which took less time? Q4: Which required less use of institutional resources? The 4 available options were: Participant's home, In hospital, No difference, or Unsure. Percentages were rounded off.

Overall number analyzed is the number of HCPs who answered any of the questions Q2, Q3, and Q4 of the HCPQ. Number analyzed is the number of HCPs who answered each sub-question of Q2, and Q3, and Q4 of the HCPQ.

Posted

Number

percentage of HCPs

Day 1 of Cycle 6 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home	Participants who completed the run-in period and were randomized to Arm C received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the hospital setting, followed by 3 cycles in the home setting (Cycle length = 21 days).

Secondary

Adjuvant Cross-over Period: Duration of Administering Treatment, According to HCPs' Responses to Question 1a to 1f of the HCPQ - Administering Treatment

HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with the preparation and/or administration of PH FDC SC completed the following questions of the HCPQ: Q1a: How long did it take to travel to the participant's home to administer PH FDC SC? Q1b: How long did it take for the participant to travel to the hospital to receive PH FDC SC? Q1c: How long did it take to administer PH FDC SC? Q1d: How long was the participant treatment time? Q1e: How much time did the participant spend in hospital? Q1f: How much time did you spend at the participant's home? From arrival to departure time.

Overall number analyzed is the number of HCPs who answered Q1a to Q1f of the HCPQ. Number analyzed is the number of HCPs who answered Q1a to Q1f of the HCPQ at the specified timepoint.

Posted

Median

Full Range

minutes

Day 1 of Cycles 3 and 6 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home	Participants who completed the run-in period and were randomized to Arm C received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the hospital setting, followed by 3 cycles in the home setting (Cycle length = 21 days).
OG001	Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital

Secondary

Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 1g, 1h, and 1i of the HCPQ - Administering Treatment

HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with the preparation and/or administration of PH FDC SC completed the following questions of the HCPQ: Q1g. Does the participant still have implanted IV access? The 2 available responses were: Yes or No. Q1h: If question 1g was answered 'No', when was the IV access removed? The 3 available responses were: After surgery and before initiating adjuvant treatment; After initiating adjuvant treatment, or Not applicable. Q1i: If question 1g was answered 'Yes', what is the main reason to keep the IV access? The 5 available responses were: Local protocol; Risk of recurrence; Participant preference; Not applicable, or Other. Percentages were rounded off.

Overall number analyzed is the number of HCPs who answered Q1g to Q1i of the HCPQ. Number analyzed is the number of HCPs who answered Q1g to Q1i of the HCPQ at the specified timepoint.

Posted

Number

percentage of HCPs

Day 1 of Cycles 3 and 6 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home	Participants who completed the run-in period and were randomized to Arm C received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the hospital setting, followed by 3 cycles in the home setting (Cycle length = 21 days).
OG001

Secondary

Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 1j, 1k, and 1l of the HCPQ - Administering Treatment

HCPs who have had experience with the preparation and/or administration of PH FDC SC completed the following questions of the HCPQ: Q1j: How long do you keep implanted IV access in early human epidermal growth factor receptor 2 (HER2)-positive breast cancer participants with pCR following surgery in your institution? The 5 available responses were: <12 months, ≥12 months, 18 months, <24 months, ≥24 months. Q1k: When is the decision point for you to decide to remove IV access for early HER2+ breast cancer participants? The 6 available responses were: Before surgery, After surgery, After PCR results, After completion of full adjuvant therapy, After completion of IV antineoplastic within adjuvant therapy, and Other. Q1l: Do you consider it necessary to keep implanted IV access knowing that the participant's treatment will be SC until the full 18 cycles? The 3 available responses were: Yes, No, and Unsure. Percentages were rounded off.

Overall number analyzed is the number of HCPs who answered any of the questions from Q1j to Q1l of the HCPQ. Number analyzed is the number of HCPs who answered each specific question (Q1j to Q1l) of the HCPQ.

Posted

Number

percentage of HCPs

Day 1 of Cycle 6 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home	Participants who completed the run-in period and were randomized to Arm C received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the hospital setting, followed by 3 cycles in the home setting (Cycle length = 21 days).

Secondary

Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Question 2 of the HCPQ - Administering Treatment

HCPs who have had experience with the preparation and/or administration of PH FDC SC completed the following question of the HCPQ: Q2: If all PH FDC SC injections were switched from an in-hospital setting to the participant's home, please indicate how strongly you agree/disagree with each of the following statements: 2a: PH FDC SC's SC route of administration allows for more flexible treatment scheduling. 2b: Frees up infusion chairs or outpatient procedure rooms used to administer SC injections. 2c: Waiting list for infusion chairs or outpatient procedure rooms is reduced. 2d: Staff's work burden is reduced, enhancing work performance. 2e: More interaction time between HCPs and participants on IV treatment. 2f: Staff has more time for administrative tasks. 2g: Participants will spend less time in hospital. 2h: Participants prefer PH FDC SC at home. The 6 available responses were: Strongly disagree, Disagree, Neutral, Agree, Strongly agree, & Not applicable.

Overall number analyzed is the number of HCPs who answered Q2 of the HCPQ. Number analyzed is the number of HCPs who answered each sub-question of Q2 (Q2a-Q2h) of the HCPQ. Percentages were rounded off.

Posted

Number

percentage of HCPs

Day 1 of Cycle 6 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home	Participants who completed the run-in period and were randomized to Arm C received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the hospital setting, followed by 3 cycles in the home setting (Cycle length = 21 days).

Secondary

Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 3 to 7 of the HCPQ - Administering Treatment

HCP was defined as any personnel involved in the drug preparation and/or drug administration processes. HCPs who have had experience with the preparation and/or administration of PH FDC SC completed the following questions of the HCPQ: Q3: Which was more convenient for the participant? Q4: Which was better for optimising participant care? Q5: Which required less use of institutional resources? Q6: Which was preferred by participants? The 4 responses available were: Participant's home, In hospital, No difference, and Unsure. Q7: How frequently would you recommend PH FDC SC at home to your participants in the future? The 3 responses available were: Always, Sometimes, and Never. Percentages were rounded off.

Overall number analyzed is the number of HCPs who answered any of the questions from Q3 to Q7 of the HCPQ. Number analyzed is the number of HCPs who answered each specific question (Q3 to Q7) of the HCPQ.

Posted

Number

percentage of HCPs

Day 1 of Cycle 6 (Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home	Participants who completed the run-in period and were randomized to Arm C received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the hospital setting, followed by 3 cycles in the home setting (Cycle length = 21 days).
OG001	Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital

Secondary

Adjuvant Phase: HRQoL Assessed by EORTC QLQ C30 Scores in Participants Treated With Trastuzumab Emtansine IV

EORTC QLQ-C30=cancer-specific instrument consisting of 30 questions that evaluated 5 aspects of participant functioning (physical, emotional, role, cognitive & social), 3 symptom scales (fatigue, nausea & vomiting & pain), GHS/QoL & 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea & financial difficulties). Functioning & symptom items used a 4-point scale, scores ranging from 1=Not at all to 4=Very much. GHS/QoL questions used a 7-point scale, scores ranging from 1=Very poor to 7=Excellent. All EORTC scales & single-item measures were linearly transformed to a score range of 0-100. High score for functional/GHS scale=high/healthy level of functioning/better HRQoL & high score for symptom scale=high level of symptom severity. A positive change from baseline=improvement & negative change=worsening in QoL & functioning scales. A positive change from baseline=deterioration & negative change=improvement in symptom scales.

Not Posted

Day 1 of Cycles 1 and 6 (1 Cycle = 21 days)

Participants

Secondary

Percentage of Participants Who Selected the Administration of PH FDC SC in the Home Setting Compared With the Hospital Setting in the Treatment Continuation Period

The percentage of participants who chose to receive PH FDC SC in the home setting or in the hospital setting during the treatment continuation period is reported.

The analysis includes all randomized participants assigned into the cross-over period who received at least one dose of PH FDC SC and entered the treatment continuation phase.

Posted

Number

Percentage of participants

Upon completion of adjuvant cross-over period (Day 1 of Cycle 8 or 9; Cycle length = 21 days)

ID	Title	Description
OG000	Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home	Participants who completed the run-in period and were randomized to Arm C received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the hospital setting, followed by 3 cycles in the home setting (Cycle length = 21 days).
OG001	Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital	Participants who completed the run-in period and were randomized to Arm D received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for the first 3 cycles in the home setting, followed by 3 cycles in the hospital setting (Cycle length = 21 days).

Secondary

Neoadjuvant Phase: Number of Participants With Adverse Events (AEs), Grade ≥ 3 AEs, Serious AEs (SAEs), and Cardiac AEs

AE was defined as any untoward medical occurrence in a clinical study participant temporally associated with use of a study treatment, whether or not considered related to the study treatment. SAE=any untoward medical occurrence that, at any dose: Results in death; Is life threatening; Requires inpatient hospitalization/prolongation of existing hospitalization; Results in persistent disability/incapacity &/or is a congenital anomaly/birth defect. Cardiac AEs=asymptomatic decline in left ventricular ejection fraction (LVEF) of ≥10% from baseline to an LVEF <50%; asymptomatic decline in LVEF requiring treatment/leading to discontinuation of study treatment; congestive heart failure (CHF). AEs ≥Grade 3=marked limitation of physical activity. Comfortable at rest, but any ordinary activity causes fatigue, palpitation/dyspnea; Inability to carry any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. Any physical activity leads to discomfort.

Neoadjuvant safety analysis set (SASab) included all randomized participants who received at least one study treatment during the neoadjuvant phase.

Posted

Count of Participants

Participants

From initiation of study treatment until 28 days after the last treatment cycle (up to approximately 7.4 months)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Secondary

Neoadjuvant Phase: Number of Participants With Premature Withdrawal From PH FDC SC and P+H IV Due to AEs

An AE was any untoward medical occurrence in a clinical study participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study intervention. Participants who discontinued the study due to AEs are reported here.

SASab included all randomized participants who received at least one study treatment during the neoadjuvant phase.

Posted

Count of Participants

Participants

Up to Cycle 8 (1 Cycle = 21 days)

ID	Title	Description
OG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).
OG001	Arm B, Neoadjuvant Phase: PH FDC SC	Participants received a loading dose of pertuzumab, 1200 mg, trastuzumab, 600 mg, and recombinant human PH20 hyaluronidase (rHuPH20), 30,000 units (U), as a SC injection on Day 1 of Cycle 1 (Cycle length = 21 days) followed by maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg and rHuPH20, 20,000 U, as a SC injection, Q3W along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).

Secondary

Adjuvant Cross-over Period: Number of Participants With AEs, Grade ≥ 3 AEs, SAEs, and Cardiac AEs

AE was defined as any untoward medical occurrence in a clinical study participant temporally associated with use of a study treatment, whether or not considered related to the study treatment. SAE=any untoward medical occurrence that, at any dose: Results in death; Is life threatening; Requires inpatient hospitalization/prolongation of existing hospitalization; Results in persistent disability/incapacity &/or is a congenital anomaly/birth defect. Cardiac AEs=asymptomatic decline in LVEF of ≥10% from baseline to an LVEF <50%; asymptomatic decline in LVEF requiring treatment/leading to discontinuation of study treatment; CHF. AEs ≥Grade 3=marked limitation of physical activity. Comfortable at rest, but any ordinary activity causes fatigue, palpitation/dyspnea; Inability to carry any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. Any physical activity leads to discomfort.

Adjuvant safety analysis set (SAScd+) included all participants with pCR who received at least one dose of PH FDC SC during the adjuvant phase. AEs for the cross-over period are pooled per treatment administration setting.

Posted

Count of Participants

Participants

From initiation of study treatment until 28 days after the last treatment cycle (up to approximately 5.8 months)

ID	Title	Description
OG000	Adjuvant Cross-Over Period: PH FDC SC in Hospital	Participants who completed the run-in period received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for 3 cycles in the hospital setting during the cross-over period (Cycle length = 21 days).

Secondary

Adjuvant Cross-over Period: Number of Participants With Premature Withdrawal From PH FDC SC Due to AEs

SAScd+ included all participants with pCR who received at least one dose of PH FDC SC during the adjuvant phase. AEs for the cross-over period are pooled per treatment administration setting.

Posted

Count of Participants

Participants

Up to Cycle 6 (Cycle length = 21 days)

ID	Title	Description
OG000	Adjuvant Cross-Over Period: PH FDC SC in Hospital	Participants who completed the run-in period received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for 3 cycles in the hospital setting during the cross-over period (Cycle length = 21 days).
OG001	Adjuvant Cross-Over Period: PH FDC SC at Home	Participants who completed the run-in period received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for 3 cycles in the home setting during the cross-over period (Cycle length = 21 days).

Secondary

Treatment Continuation Period and Trastuzumab Emtansine IV Period: Number of Participants With AEs, Grade ≥ 3 AEs, SAEs, and Cardiac AEs

AE was defined as any untoward medical occurrence in a clinical study participant temporally associated with use of a study treatment, whether or not considered related to the study treatment. SAE=any untoward medical occurrence that, at any dose: Results in death; Is life threatening; Requires inpatient hospitalization/prolongation of existing hospitalization; Results in persistent disability/incapacity &/or is a congenital anomaly/birth defect. Cardiac AEs=asymptomatic decline in LVEF of ≥10% from baseline to an LVEF <50%; asymptomatic decline in LVEF requiring treatment/leading to discontinuation of study treatment; CHF. AEs ≥Grade 3=marked limitation of physical activity. Comfortable at rest, but any ordinary activity causes fatigue, palpitation/dyspnea; Inability to carry any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. Any physical activity leads to discomfort.

Not Posted

From initiation of study treatment until 28 days after the last treatment cycle (up to approximately 3.5 years)

Participants

Secondary

Treatment Continuation Period and Trastuzumab Emtansine IV Period: Number of Participants With Premature Withdrawal From PH FDC SC and Trastuzumab Emtansine IV Due to AEs

Not Posted

From initiation of study treatment in the adjuvant phase until 28 days after the last treatment cycle (up to approximately 3.5 years)

Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).	0	115	19	115	113	115
EG001	Arm B, Neoadjuvant Phase: PH FDC SC	Participants received a loading dose of pertuzumab, 1200 mg, trastuzumab, 600 mg, and recombinant human PH20 hyaluronidase (rHuPH20), 30,000 units (U), as a SC injection on Day 1 of Cycle 1 (Cycle length = 21 days) followed by maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg and rHuPH20, 20,000 U, as a SC injection, Q3W along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).	4	228	43	228	222	228
EG002	Adjuvant Run-in Phase: PH FDC SC in Hospital	Participants who achieved pathologic complete response (pCR) after surgery received a loading dose of pertuzumab, 1200 mg, trastuzumab, 600 mg, and rHuPH20, 30,000 U, as a SC injection on Day 1 of Cycle 1 followed by maintenance dose of pertuzumab, 600 mg, trastuzumab, 600 mg and rHuPH20, 20,000 U, as a SC injection, on Day 1 of Cycle 2 (Cycle length = 21 days).	0	194	3	194	84	194
EG003	Adjuvant Cross-Over Phase: PH FDC SC in Hospital	Participants who completed the run-in period received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for 3 cycles in the hospital setting during the cross-over period (Cycle length = 21 days).	0	190	1	190	77	190
EG004	Adjuvant Cross-Over Phase: PH FDC SC at Home	Participants who completed the run-in period received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection for 3 cycles in the home setting during the cross-over period (Cycle length = 21 days).	0	191	1	191	64	191
EG005	Adjuvant Continuation Phase: PH FDC SC in Hospital	Participants who completed the cross-over period and opted to receive further treatment in the hospital setting received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection up to a maximum of 18 cycles (Cycle length = 21 days).	0	84	1	84	26	84
EG006	Adjuvant Continuation Phase: PH FDC SC at Home	Participants who completed the cross-over period and opted to receive further treatment at home received maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg, and rHuPH20, 20,000 U, as a SC injection up to a maximum of 18 cycles (Cycle length = 21 days).	0	114	0	114	31	114
EG007	Arm E, Adjuvant Phase: Trastuzumab Emtansine IV	Participants who did not achieve pCR after surgery received trastuzumab emtansine, 3.6 mg/kg, as an IV infusion for 90 minutes as an initial dose. Thereafter, participants received trastuzumab emtansine, 3.6 mg/kg, as an IV infusion for 30 minutes, Q3W for 14 cycles (Cycle length = 21 days).	1	117	9	117	107	117

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG0002 events1 affected115 at risk EG0014 events4 affected228 at risk EG0020 events0 affected194 at risk EG0030 events0 affected190 at risk EG0040 events0 affected191 at risk EG0050 events0 affected84 at risk EG0060 events0 affected114 at risk EG0070 events0 affected117 at risk
Atypical haemolytic uraemic syndrome	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0018 events7 affected228 at risk EG0020 events0 affected194 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG0002 events2 affected115 at risk EG0015 events4 affected228 at risk EG0020 events0 affected194 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0014 events3 affected228 at risk EG0020 events0 affected194 at risk EG003
Thrombotic thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG0004 events4 affected115 at risk EG0018 events7 affected228 at risk EG0020 events0 affected194 at risk EG003
Diarrhoea haemorrhagic	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0013 events3 affected228 at risk EG0020 events0 affected194 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0012 events2 affected228 at risk EG0020 events0 affected194 at risk EG003
Asthenia	General disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Pyrexia	General disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Abdominal sepsis	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Abscess limb	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Breast abscess	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Cellulitis	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Enteritis infectious	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0002 events1 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Infected seroma	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Infection	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Malaria	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Mastitis	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0021 events1 affected194 at risk EG003
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Pneumonia	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Postoperative wound infection	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0002 events2 affected115 at risk EG0010 events0 affected228 at risk EG0021 events1 affected194 at risk EG003
Pseudomonal sepsis	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Sepsis	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Wound infection	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0012 events2 affected228 at risk EG0020 events0 affected194 at risk EG003
Seroma	Injury, poisoning and procedural complications	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0021 events1 affected194 at risk EG003
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Coma scale abnormal	Investigations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Ejection fraction decreased	Investigations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Neutrophil count decreased	Investigations	MedDRA version 27.1	Systematic Assessment	EG0003 events2 affected115 at risk EG0013 events3 affected228 at risk EG0020 events0 affected194 at risk EG003
Neutrophil count increased	Investigations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Platelet count decreased	Investigations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0012 events2 affected228 at risk EG0020 events0 affected194 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Seizure	Nervous system disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Syncope	Nervous system disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Anxiety	Psychiatric disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Cystitis haemorrhagic	Renal and urinary disorders	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Adnexa uteri mass	Reproductive system and breast disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0012 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA version 27.1	Systematic Assessment	EG0002 events2 affected115 at risk EG0011 events1 affected228 at risk EG0020 events0 affected194 at risk EG003
Hypotension	Vascular disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0012 events2 affected228 at risk EG0020 events0 affected194 at risk EG003
Hypovolaemic shock	Vascular disorders	MedDRA version 27.1	Systematic Assessment	EG0001 events1 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Multiple organ dysfunction syndrome	General disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Sinusitis	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Soft tissue infection	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003
Device breakage	Product Issues	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0010 events0 affected228 at risk EG0020 events0 affected194 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG00082 events61 affected115 at risk EG001128 events96 affected228 at risk EG0020 events0 affected194 at risk EG0035 events5 affected190 at risk EG0041 events1 affected191 at risk EG0051 events1 affected84 at risk EG0062 events2 affected114 at risk EG00729 events20 affected117 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG00029 events13 affected115 at risk EG00147 events26 affected228 at risk EG0021 events1 affected194 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG00017 events8 affected115 at risk EG00118 events12 affected228 at risk EG0020 events0 affected194 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG00036 events22 affected115 at risk EG00197 events60 affected228 at risk EG0022 events2 affected194 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA version 27.1	Systematic Assessment	EG00022 events12 affected115 at risk EG00133 events21 affected228 at risk EG0020 events0 affected194 at risk EG003
Dry eye	Eye disorders	MedDRA version 27.1	Systematic Assessment	EG0004 events4 affected115 at risk EG00120 events15 affected228 at risk EG0020 events0 affected194 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG0007 events5 affected115 at risk EG00121 events18 affected228 at risk EG0022 events2 affected194 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG00012 events9 affected115 at risk EG00120 events16 affected228 at risk EG0022 events2 affected194 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG00014 events14 affected115 at risk EG00145 events29 affected228 at risk EG0022 events2 affected194 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG000145 events72 affected115 at risk EG001274 events147 affected228 at risk EG00214 events12 affected194 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG00020 events14 affected115 at risk EG00132 events28 affected228 at risk EG0020 events0 affected194 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG0007 events7 affected115 at risk EG00115 events14 affected228 at risk EG0021 events1 affected194 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG00094 events64 affected115 at risk EG001245 events136 affected228 at risk EG0025 events5 affected194 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG00017 events13 affected115 at risk EG00137 events31 affected228 at risk EG0020 events0 affected194 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA version 27.1	Systematic Assessment	EG00034 events25 affected115 at risk EG00181 events57 affected228 at risk EG0021 events1 affected194 at risk EG003
Asthenia	General disorders	MedDRA version 27.1	Systematic Assessment	EG00030 events18 affected115 at risk EG00154 events36 affected228 at risk EG0023 events3 affected194 at risk EG003
Fatigue	General disorders	MedDRA version 27.1	Systematic Assessment	EG00059 events41 affected115 at risk EG001131 events86 affected228 at risk EG0029 events9 affected194 at risk EG003
Influenza like illness	General disorders	MedDRA version 27.1	Systematic Assessment	EG0005 events3 affected115 at risk EG00112 events12 affected228 at risk EG0022 events2 affected194 at risk EG003
Mucosal inflammation	General disorders	MedDRA version 27.1	Systematic Assessment	EG00026 events19 affected115 at risk EG00146 events35 affected228 at risk EG0020 events0 affected194 at risk EG003
Oedema peripheral	General disorders	MedDRA version 27.1	Systematic Assessment	EG00011 events9 affected115 at risk EG00117 events15 affected228 at risk EG0021 events1 affected194 at risk EG003
Pain	General disorders	MedDRA version 27.1	Systematic Assessment	EG0008 events7 affected115 at risk EG00113 events11 affected228 at risk EG0020 events0 affected194 at risk EG003
Pyrexia	General disorders	MedDRA version 27.1	Systematic Assessment	EG0006 events6 affected115 at risk EG00131 events27 affected228 at risk EG0024 events4 affected194 at risk EG003
COVID-19	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0004 events4 affected115 at risk EG00110 events10 affected228 at risk EG0021 events1 affected194 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG0005 events3 affected115 at risk EG00117 events15 affected228 at risk EG0021 events1 affected194 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA version 27.1	Systematic Assessment	EG00015 events13 affected115 at risk EG00131 events26 affected228 at risk EG0020 events0 affected194 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA version 27.1	Systematic Assessment	EG00015 events14 affected115 at risk EG00112 events12 affected228 at risk EG0020 events0 affected194 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA version 27.1	Systematic Assessment	EG0008 events8 affected115 at risk EG0015 events5 affected228 at risk EG0023 events3 affected194 at risk EG003
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA version 27.1	Systematic Assessment	EG0000 events0 affected115 at risk EG0013 events3 affected228 at risk EG00227 events27 affected194 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA version 27.1	Systematic Assessment	EG00016 events12 affected115 at risk EG00136 events26 affected228 at risk EG0023 events3 affected194 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA version 27.1	Systematic Assessment	EG00014 events11 affected115 at risk EG00127 events20 affected228 at risk EG0021 events1 affected194 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA version 27.1	Systematic Assessment	EG0007 events5 affected115 at risk EG0016 events6 affected228 at risk EG0022 events2 affected194 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA version 27.1	Systematic Assessment	EG00010 events7 affected115 at risk EG00111 events8 affected228 at risk EG0020 events0 affected194 at risk EG003
Neutrophil count decreased	Investigations	MedDRA version 27.1	Systematic Assessment	EG00017 events8 affected115 at risk EG00167 events30 affected228 at risk EG0020 events0 affected194 at risk EG003
Platelet count decreased	Investigations	MedDRA version 27.1	Systematic Assessment	EG0008 events5 affected115 at risk EG00111 events10 affected228 at risk EG0021 events1 affected194 at risk EG003
Weight decreased	Investigations	MedDRA version 27.1	Systematic Assessment	EG00011 events10 affected115 at risk EG00117 events17 affected228 at risk EG0020 events0 affected194 at risk EG003
White blood cell count decreased	Investigations	MedDRA version 27.1	Systematic Assessment	EG0004 events4 affected115 at risk EG00121 events12 affected228 at risk EG0026 events4 affected194 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA version 27.1	Systematic Assessment	EG00015 events15 affected115 at risk EG00156 events45 affected228 at risk EG0021 events1 affected194 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA version 27.1	Systematic Assessment	EG0009 events8 affected115 at risk EG0013 events3 affected228 at risk EG0020 events0 affected194 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 27.1	Systematic Assessment	EG00016 events13 affected115 at risk EG00125 events23 affected228 at risk EG00211 events11 affected194 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 27.1	Systematic Assessment	EG0009 events9 affected115 at risk EG00118 events17 affected228 at risk EG0020 events0 affected194 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA version 27.1	Systematic Assessment	EG00019 events13 affected115 at risk EG00135 events28 affected228 at risk EG0022 events2 affected194 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 27.1	Systematic Assessment	EG0005 events5 affected115 at risk EG00110 events10 affected228 at risk EG0022 events2 affected194 at risk EG003
Dizziness	Nervous system disorders	MedDRA version 27.1	Systematic Assessment	EG0008 events8 affected115 at risk EG00115 events11 affected228 at risk EG0021 events1 affected194 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA version 27.1	Systematic Assessment	EG00015 events13 affected115 at risk EG00136 events33 affected228 at risk EG0020 events0 affected194 at risk EG003
Headache	Nervous system disorders	MedDRA version 27.1	Systematic Assessment	EG00016 events16 affected115 at risk EG00144 events37 affected228 at risk EG00210 events9 affected194 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA version 27.1	Systematic Assessment	EG00016 events16 affected115 at risk EG00145 events41 affected228 at risk EG0025 events5 affected194 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA version 27.1	Systematic Assessment	EG0006 events5 affected115 at risk EG00125 events21 affected228 at risk EG0022 events2 affected194 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA version 27.1	Systematic Assessment	EG00011 events9 affected115 at risk EG00120 events20 affected228 at risk EG0022 events2 affected194 at risk EG003
Anxiety	Psychiatric disorders	MedDRA version 27.1	Systematic Assessment	EG0008 events8 affected115 at risk EG0017 events7 affected228 at risk EG0022 events2 affected194 at risk EG003
Insomnia	Psychiatric disorders	MedDRA version 27.1	Systematic Assessment	EG00012 events11 affected115 at risk EG00115 events15 affected228 at risk EG0024 events4 affected194 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA version 27.1	Systematic Assessment	EG0004 events4 affected115 at risk EG00113 events12 affected228 at risk EG0021 events1 affected194 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 27.1	Systematic Assessment	EG00012 events12 affected115 at risk EG00122 events21 affected228 at risk EG0024 events4 affected194 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 27.1	Systematic Assessment	EG0006 events6 affected115 at risk EG00110 events9 affected228 at risk EG0022 events2 affected194 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA version 27.1	Systematic Assessment	EG00014 events10 affected115 at risk EG00131 events22 affected228 at risk EG0020 events0 affected194 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA version 27.1	Systematic Assessment	EG00060 events57 affected115 at risk EG001131 events124 affected228 at risk EG0023 events3 affected194 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA version 27.1	Systematic Assessment	EG0006 events5 affected115 at risk EG00118 events17 affected228 at risk EG0021 events1 affected194 at risk EG003
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA version 27.1	Systematic Assessment	EG0006 events6 affected115 at risk EG0015 events5 affected228 at risk EG0020 events0 affected194 at risk EG003
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA version 27.1	Systematic Assessment	EG0005 events4 affected115 at risk EG00113 events13 affected228 at risk EG0020 events0 affected194 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA version 27.1	Systematic Assessment	EG00010 events10 affected115 at risk EG00116 events15 affected228 at risk EG0024 events4 affected194 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA version 27.1	Systematic Assessment	EG00013 events11 affected115 at risk EG00121 events20 affected228 at risk EG0022 events2 affected194 at risk EG003
Flushing	Vascular disorders	MedDRA version 27.1	Systematic Assessment	EG0007 events6 affected115 at risk EG0014 events4 affected228 at risk EG0020 events0 affected194 at risk EG003
Hot flush	Vascular disorders	MedDRA version 27.1	Systematic Assessment	EG0004 events4 affected115 at risk EG00115 events14 affected228 at risk EG0021 events1 affected194 at risk EG003

ID	Term
D001943	Breast Neoplasms
D058922	Inflammatory Breast Neoplasms
D057240	Patient Preference

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D017060	Patient Satisfaction
D000074822	Treatment Adherence and Compliance
D015438	Health Behavior
D001519	Behavior

ID	Term
D000068878	Trastuzumab
D007279	Injections, Subcutaneous
C485206	pertuzumab
D000080044	Ado-Trastuzumab Emtansine
D013514	Surgical Procedures, Operative
D011878	Radiotherapy

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D007267	Injections
D004333	Drug Administration Routes
D004358	Drug Therapy
D013812	Therapeutics
D008453	Maytansine
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D047029	Lactams, Macrocyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds

ID	Title	Description
BG000	Arm A, Neoadjuvant Phase: P+H IV	Participants received a loading dose of pertuzumab, 840 milligrams (mg), and trastuzumab, 8 milligrams per kilogram (mg/kg), as an IV infusion on Day 1 of Cycle 1 (Cycle length = 21 days), followed by maintenance doses of pertuzumab, 420 mg and trastuzumab, 6 mg/kg, as an IV infusion, every 3 weeks (Q3W) along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).
BG001	Arm B, Neoadjuvant Phase: PH FDC SC	Participants received a loading dose of pertuzumab, 1200 mg, trastuzumab, 600 mg, and recombinant human PH20 hyaluronidase (rHuPH20), 30,000 units (U), as a SC injection on Day 1 of Cycle 1 (Cycle length = 21 days) followed by maintenance doses of pertuzumab, 600 mg, trastuzumab, 600 mg and rHuPH20, 20,000 U, as a SC injection, Q3W along with neoadjuvant chemotherapy based on investigator's choice, for 6-8 cycles (depending on the chosen neoadjuvant scheme).
BG002	Total	Total of all reporting groups