A Study to Evaluate Patient Preference for Home Administration of Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Administration in Participants With Early or Locally Advanced/Inflammatory HER2-Positive Breast Cancer

• Fixed Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Use (PH FDC SC) (Drug), also known as PHESGO®, Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf, Pertuzumab, Trastuzumab, and rHuPH20, RO7198574, RG6264: 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).
• Pertuzumab IV (Drug), also known as Perjeta®, RO4368451: Pertuzumab is given as a fixed dose of 840 mg intravenous (IV) loading dose and then 420 mg IV for subsequent maintenance doses once every 3 weeks.
• Trastuzumab IV (Drug), also known as Herceptin®, RO0452317: Trastuzumab is given as an 8 milligram per kilogram (mg/kg) intravenous (IV) loading dose and then 6 mg/kg IV for subsequent maintenance doses once every 3 weeks.
• Trastuzumab Emtansine (Drug), also known as Kadcyla®, ado-trastuzumab emtansine, T-DM1, RO5304020: Trastuzumab emtansine will be given at a dose of 3.6 mg/kg by intravenous (IV) infusion, once every 3 weeks.
• Investigator's Choice of Chemotherapy (Drug): Option 1: Docetaxel and carboplatin once every 3 weeks for 6 cycles; Option 2: Doxorubicin plus cyclophosphamide once every 3 weeks for 4 cycles, followed by a taxane (docetaxel once every 3 weeks for 4 cycles or paclitaxel once every week for 12 cycles); Option 3: Dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks for 4 cycles, followed by a taxane (docetaxel once every 3 weeks for 4 cycles or paclitaxel once every week for 12 cycles).
• Surgery (Procedure): After completing their neoadjuvant therapy, participants will undergo surgical resection for early or locally advanced HER2+ breast cancer (if eligible for surgery). Participants may undergo breast-conserving surgery or mastectomy according to routine clinical practice. The surgery cannot be performed ≤2 weeks from the last systemic neoadjuvant therapy and must be performed ≤6 weeks after the last systemic neoadjuvant therapy.
• Radiotherapy (Radiation): After surgery, radiotherapy is to be given as clinically indicated and as per local practice or institutional standards. The selected radiotherapy regimen should be initiated within 4 weeks after surgery.

Primary outcomes

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

Secondary outcomes

• Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 1a of HCPQ - Drug Preparation Area [Day 1 of Cycles 1-8 (Cycle length = 21 days)]: 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.
• Neoadjuvant Phase: Duration of Treatment Preparation, According to Healthcare Professionals' Responses to Question 1b of HCPQ - Drug Preparation Area [Day 1 of Cycles 1-8 (Cycle length = 21 days)]: 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.
• Neoadjuvant Phase: Percentage of HCPs by Their Response to Question 2 of the HCPQ - Drug Preparation Area [Up to Day 1 of Cycle 8 (Cycle length = 21 days)]: 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.
• Neoadjuvant Phase: Percentage of HCPs by Their Responses to Questions 1a-1e of the HCPQ - Administering Treatment [Day 1 of Cycles 1-8 (Cycle length = 21 days)]: 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.
• Neoadjuvant Phase: Duration of Treatment Administration According to HCPs' Responses to Questions 1c (Sub-part), 1f, and 1g of the HCPQ - Administering Treatment [Day 1 of Cycles 1-8 (Cycle length = 21 days)]: 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.
• Neoadjuvant Phase: Percentage of HCPs by Their Response to Question 2 (2a to 2e) of the HCPQ - Administering Treatment [Up to Cycle 8 (Cycle length = 21 days)]: 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.
• Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 2 (2f to 2j) of the HCPQ - Administering Treatment [Up to Cycle 8 (Cycle length = 21 days)]: 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.
• Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 3 to 11 of the HCPQ - Administering Treatment [Up to Cycle 8 (Cycle length = 21 days)]: 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.
• Percentage of Participants Who Achieved pCR Post-surgery [Up to approximately 7.8 months]: 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.
• 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 [Baseline, Day 1 of Cycles 6 and 8 (Cycle length = 21 days)]: 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.
• Adjuvant Phase: Change From Baseline in HRQoL Assessed by EORTC QLQ C30 Scores [Baseline (Cycle 1) of Run-in Period; Day 1 of Cycles 1, 3, and 6 in the Cross-over Period (Cycle length = 21 days)]: 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.
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 1a and 1c of the HCPQ - Drug Preparation Area [Day 1 of Cycles 3 and 6 (Cycle length = 21 days)]: 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.
• Adjuvant Cross-over Period: Duration of Treatment Preparation, According to HCPs' Responses to Question 1b of the HCPQ - Drug Preparation Area [Day 1 of Cycles 3 and 6 (Cycle length = 21 days)]: 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.
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 2, 3 and 4 of the HCPQ - Drug Preparation Area [Day 1 of Cycle 6 (Cycle length = 21 days)]: 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.
• Adjuvant Cross-over Period: Duration of Administering Treatment, According to HCPs' Responses to Question 1a to 1f of the HCPQ - Administering Treatment [Day 1 of Cycles 3 and 6 (Cycle length = 21 days)]: 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.
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 1g, 1h, and 1i of the HCPQ - Administering Treatment [Day 1 of Cycles 3 and 6 (Cycle length = 21 days)]: 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.
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 1j, 1k, and 1l of the HCPQ - Administering Treatment [Day 1 of Cycle 6 (Cycle length = 21 days)]: 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.
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Question 2 of the HCPQ - Administering Treatment [Day 1 of Cycle 6 (Cycle length = 21 days)]: 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.
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 3 to 7 of the HCPQ - Administering Treatment [Day 1 of Cycle 6 (Cycle length = 21 days)]: 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.
• Adjuvant Phase: HRQoL Assessed by EORTC QLQ C30 Scores in Participants Treated With Trastuzumab Emtansine IV [Day 1 of Cycles 1 and 6 (1 Cycle = 21 days)]: 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.
• 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 [Upon completion of adjuvant cross-over period (Day 1 of Cycle 8 or 9; Cycle length = 21 days)]: 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.
• Neoadjuvant Phase: Number of Participants With Adverse Events (AEs), Grade ≥ 3 AEs, Serious AEs (SAEs), and Cardiac AEs [From initiation of study treatment until 28 days after the last treatment cycle (up to approximately 7.4 months)]: 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 Phase: Number of Participants With Premature Withdrawal From PH FDC SC and P+H IV Due to AEs [Up to Cycle 8 (1 Cycle = 21 days)]: 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.
• Adjuvant Cross-over Period: Number of Participants With AEs, Grade ≥ 3 AEs, SAEs, and Cardiac AEs [From initiation of study treatment until 28 days after the last treatment cycle (up to approximately 5.8 months)]: 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 Cross-over Period: Number of Participants With Premature Withdrawal From PH FDC SC Due to AEs [Up to Cycle 6 (Cycle length = 21 days)]: 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.
• Treatment Continuation Period and Trastuzumab Emtansine IV Period: Number of Participants With AEs, Grade ≥ 3 AEs, SAEs, and Cardiac AEs [From initiation of study treatment until 28 days after the last treatment cycle (up to approximately 3.5 years)]: 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.
• 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 [From initiation of study treatment in the adjuvant phase until 28 days after the last treatment cycle (up to approximately 3.5 years)]: 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 discontinue study due to AEs will be reported.

Sex: All, ages: 18 Years to any

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)

Participant flow

Outcome results

• 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) (Primary), Number, percentage of participants: Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home 69.0; Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital 59.0
• Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 1a of HCPQ - Drug Preparation Area (Secondary), Number, percentage of HCPs: Arm A, Neoadjuvant Phase: P+H IV 0; Arm B, Neoadjuvant Phase: PH FDC SC 100
• Neoadjuvant Phase: Duration of Treatment Preparation, According to Healthcare Professionals' Responses to Question 1b of HCPQ - Drug Preparation Area (Secondary), Median, minutes: Arm A, Neoadjuvant Phase: P+H IV 20.0 (1 to 120); Arm B, Neoadjuvant Phase: PH FDC SC 5.0 (0 to 30)
• Neoadjuvant Phase: Percentage of HCPs by Their Response to Question 2 of the HCPQ - Drug Preparation Area (Secondary), Number, percentage of HCPs: Arm A, Neoadjuvant Phase: P+H IV 1.1; Arm B, Neoadjuvant Phase: PH FDC SC 2.4
• Neoadjuvant Phase: Percentage of HCPs by Their Responses to Questions 1a-1e of the HCPQ - Administering Treatment (Secondary), Number, percentage of HCPs: Arm A, Neoadjuvant Phase: P+H IV 0; Arm B, Neoadjuvant Phase: PH FDC SC 100
• Neoadjuvant Phase: Duration of Treatment Administration According to HCPs' Responses to Questions 1c (Sub-part), 1f, and 1g of the HCPQ - Administering Treatment (Secondary), Median, minutes: Arm A, Neoadjuvant Phase: P+H IV 5.0 (1 to 150); Arm B, Neoadjuvant Phase: PH FDC SC 5.0 (1 to 308)
• Neoadjuvant Phase: Percentage of HCPs by Their Response to Question 2 (2a to 2e) of the HCPQ - Administering Treatment (Secondary), Number, percentage of HCPs: Arm A, Neoadjuvant Phase: P+H IV 1.0; Arm B, Neoadjuvant Phase: PH FDC SC 3.0
• Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 2 (2f to 2j) of the HCPQ - Administering Treatment (Secondary), Number, percentage of HCPs: Arm A, Neoadjuvant Phase: P+H IV 0; Arm B, Neoadjuvant Phase: PH FDC SC 2.4
• Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 3 to 11 of the HCPQ - Administering Treatment (Secondary), Number, percentage of HCPs: Arm A, Neoadjuvant Phase: P+H IV 8.0; Arm B, Neoadjuvant Phase: PH FDC SC 1.2
• Percentage of Participants Who Achieved pCR Post-surgery (Secondary), Number, percentage of participants: Arm A, Neoadjuvant Phase: P+H IV 60.2; Arm B, Neoadjuvant Phase: PH FDC SC 60.9
• 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 (Secondary), Mean, score on a scale: Arm A, Neoadjuvant Phase: P+H IV 79.86 +/- 18.40; Arm B, Neoadjuvant Phase: PH FDC SC 75.97 +/- 20.92
• Adjuvant Phase: Change From Baseline in HRQoL Assessed by EORTC QLQ C30 Scores (Secondary), Mean, score on a scale: Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home 76.98 +/- 17.09; Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital 71.79 +/- 18.63
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 1a and 1c of the HCPQ - Drug Preparation Area (Secondary), Number, percentage of HCPs: Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home 0; Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital 90.6
• Adjuvant Cross-over Period: Duration of Treatment Preparation, According to HCPs' Responses to Question 1b of the HCPQ - Drug Preparation Area (Secondary), Median, minutes: Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home 5.0 (1 to 33); Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital 5.0 (1 to 30)
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 2, 3 and 4 of the HCPQ - Drug Preparation Area (Secondary), Number, percentage of HCPs: Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home 2.5; Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital 1.3
• Adjuvant Cross-over Period: Duration of Administering Treatment, According to HCPs' Responses to Question 1a to 1f of the HCPQ - Administering Treatment (Secondary), Median, minutes: Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home 82.5 (60 to 105); Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital 60.0 (11 to 540)
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 1g, 1h, and 1i of the HCPQ - Administering Treatment (Secondary), Number, percentage of HCPs: Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home 35.6; Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital 14.5
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 1j, 1k, and 1l of the HCPQ - Administering Treatment (Secondary), Number, percentage of HCPs: Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home 10.7; Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital 27.0
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Question 2 of the HCPQ - Administering Treatment (Secondary), Number, percentage of HCPs: Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home 6.3; Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital 0
• Adjuvant Cross-over Period: Percentage of HCPs by Their Responses to Questions 3 to 7 of the HCPQ - Administering Treatment (Secondary), Number, percentage of HCPs: Arm C, Adjuvant Cross-over Phase: PH FDC SC in Hospital, Then at Home 84.0; Arm D, Adjuvant Cross-Over Phase: PH FDC SC at Home, Then in Hospital 45.9
• 8 more outcome measures not shown.

Adverse events

Time frame: From initiation of study treatment until 28 days after the last treatment cycle (Neoadjuvant phase: up to 7.4 months; Adjuvant phase: up to 12.3 months)

Serious adverse events by term

10 more terms not shown.

Other adverse events by term

2 more terms not shown.

• Study Protocol (PDF, 2024-01-25)
• Statistical Analysis Plan (PDF, 2025-04-11)

• Clinical Trials, Study director, Hoffmann-La Roche

NIH grants: 2023