Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Oculocerebral Syndrome With Hypopigmentation

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Pertuzumab

Antineoplastic Agents, Immunological

In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.

In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.

PH FDC SC will be administered subcutaneously (SC) at a fixed non-weight-based dose. A loading dose of 1200 mg pertuzumab and 600 mg trastuzumab is then followed by a maintenance dose of 600 mg pertuzumab and 600 mg trastuzumab once every 3 weeks (Q3W).

Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC)

Pertuzumab will be administered intravenously (IV) as a fixed non-weight-based dose of 840-mg IV loading dose and then 420-mg IV maintenance dose Q3W.

Pertuzumab IV

Trastuzumab will be administered intravenously (IV) as an 8-mg/kg IV loading dose and then 6 mg/kg IV maintenance dose Q3W.

Trastuzumab IV

Clinical Trials

This is a Phase II, randomized, multicentre, multinational, open-label, cross-over study in adult patients who have completed neoadjuvant chemotherapy with neoadjuvant pertuzumab and trastuzumab and have undergone surgical treatment of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. The study will consist of two adjuvant treatment periods: a treatment cross-over period and a treatment continuation period. It will evaluate participant-reported preference for a subcutaneously administered fixed-dose combination formulation (FDC SC) of pertuzumab and trastuzumab compared with intravenously (IV) administered pertuzumab and trastuzumab formulations. The study will also evaluate participant-reported satisfaction with pertuzumab and trastuzumab FDC SC and health-related quality of life outcomes; healthcare professionals' perceptions of time/resource use and convenience of pertuzumab and trastuzumab FDC SC compared with pertuzumab and trastuzumab IV formulations; as well as the safety and efficacy of each study regimen.

A Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Participants With HER2-Positive Early Breast Cancer

A Randomized, Multicenter, Open-Label Cross-Over Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Patients With HER2-Positive Early Breast Cancer

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Question 1 of the Patient Preference Questionnaire (PPQ) asked participants the following question: "All things considered, which method of administration did you prefer?" The three available options for a participant's response were: IV, SC, or No preference. A point estimate with associated exact Clopper-Pearson binomial 95% confidence interval was calculated only for the percentage of participants who preferred PH FDC SC.

Question 1 of the Patient Preference Questionnaire (PPQ) was as follows: "All things considered, which method of administration did you prefer?" The available options for a participant's response were IV, SC, or No preference. In Question 2 of the PPQ, participants who reported a preference for one of the two administration routes in Question 1 of the PPQ were asked to rate the strength of their preference (very strong, fairly strong, not very strong).

In Question 3 of the PPQ, participants who reported a preference for one of the two administration routes in Question 1 of the PPQ were asked to provide the two main reasons for their preference. The five available options for a participant's response were: Feels less emotionally distressing; Requires less time in the clinic; Lower level of injection-site pain; Feels more comfortable during administration; and Other reason.

The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of each mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on five domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received per arm during the Cross-Over Period. Question 1 of the TASQ-IV/TASQ-SC is one of two items in the Satisfaction domain, with participants providing their answers to the following question: "How satisfied or dissatisfied were you with the IV infusion/SC injection?" The five available options for a participant's response were: very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied, and very dissatisfied.

The TASQ is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains: Physical Impact (3 items: Question \[Q\]2. Pain, Q3. Swelling, Q4. Redness), Psychological Impact (1 item: Q5. Feeling restricted), Impact on Activities of Daily Living (1 item: Q8. Lost/gained time), Convenience (2 items: Q6. Is it convenient?, Q7. Bothered by the amount of time?), and Satisfaction (2 items: Q1. How satisfied or dissatisfied are you with treatment?, Q12: Would you recommend the way you received the treatment?). In addition, 3 questions in the TASQ (Q9, Q10, Q11) are not part of the domains. Responses for the 3 domains that contain more than 1 item were scored from 0 to 100, with a higher score indicating a better outcome. Responses for the 2 domains with 1 item were scored from 1 to 5, with a higher score indicating a better outcome.

The TASQ is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains. In addition, 3 questions (Q.9-11) are not part of the domains. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received per arm during the Cross-Over Period. Question 9 asked the participant, "When you receive the IV infusion/SC injection treatment, are you able to talk to your nurse and/or doctor as much as you would like about your illness?" There were five available response options: a) Yes, I had more than enough time to talk to my nurse and/or doctor; b) Yes, but I would have liked more time to talk to my nurse and/or doctor; c) It does not matter to me if I have time to talk to my nurse and/or doctor during my treatment; d) No, I did not have enough time to talk to my nurse and/or doctor; and e) No, I did not talk to my nurse and/or doctor at all.

The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains (questions \[Q\] 1 to 8 and Q12): Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. In addition, 3 questions in the TASQ-IV/-SC (Q 9-11) are not part of the domains. The TASQ-IV/-SC were administered at treatment Cycles 3 and 6 according to the order of treatment received in each study arm during the Cross-Over Period. Question 10 of the TASQ-IV/-SC asked the participant "Does the IV infusion/SC injection impact the amount of time you have to talk to your nurse and/or doctor about your illness and other concerns?" There were two available options for the participant's response: Yes or No.

The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains (questions \[Q\] 1 to 8 and Q12): Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. In addition, 3 questions in the TASQ-IV/-SC (Q 9-11) are not part of the domains. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received during the Cross-Over Period. Question 11 of the TASQ-IV/-SC asked the participant, "There are two ways to get cancer treatment: a) IV infusion given through a port or small tube; b) SC (subcutaneous) injection in your thigh. Which would you prefer?" There were three available options for the participant's response: IV, SC, or No Preference.

At treatment Cycle 6, Day 1, participants were expected to select the study treatment formulation (PH FDC SC or P+H IV) they would receive during the Treatment Continuation Period (starting at Cycle 7) to complete their 18 cycles of neo/adjuvant HER2-targeted treatment. Additionally, for each participant's preference category (SC, IV, and No preference) as per the question 1 of the patient preference questionnaire (PPQ), the percentage of participants who selected each treatment administration route for the Treatment Continuation Period (PH FDC SC or P+H IV) was summarized.

The Healthcare Professional Questionnaire (HCPQ)-Treatment Room Question 1 was completed at each treatment cycle of the Treatment Cross-Over Period by the healthcare professionals (HCPs) who administered treatment to the study's participants. HCPs responded to the following parts of Question 1 that sought to evaluate the amount of time it took to complete activities related to treatment administration: "If new IV access was needed for this cycle of treatment, please indicate what type of IV access was provided (central venous catheter, peripherally inserted central catheter, or peripheral vein cannulation) and how long (in minutes) this took to set up (only for participants receiving IV treatment)? How long (in minutes) did it take to administer the treatment, i.e. total infusion duration? How long (in minutes) was the patient in the Treatment Room for in total?"

HCPs who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Question 2: "If all P+H IV infusions are switched to FDC SC injections, please indicate how strongly you agree or disagree with each of the following statements: a) Patients will be moved outside of infusion unit to receive FDC SC; b) FDC SC route will allow more flexible scheduling; c) More patients will be treated in the infusion unit; d) Waiting list for any P+H IV treatment at the infusion unit will be reduced; e) Staff resources will be redistributed to other departments of the hospital; f) There will still be sufficient interaction time between HCPs and patients; g) Staff will spend more time for further education/development; h) Staff will dedicate more time attending to administrative tasks for Perjeta-Herceptin patients; i) Patients will spend less time in the care unit; j) Administration by FDC SC injection is preferred by patients."

Healthcare professionals (HCPs) who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Questions 3 to 7: "Looking back over the Perjeta-Herceptin treatment sessions, please indicate based on your opinion which administration method: Q3. Which Method Was Most Convenient for the Patient? Q4. Which Method Was Best for Optimizing Patient Care in Your Centre? Q5. Which Method Took the Least Time from Start to Finish of Administration? Q6. Which Method Required the Least Resource Use for Administration? Q7. Which Method Was Preferred by Patients?" The four available response options were: P+H IV, FDC SC, No Difference, and Unsure.

Healthcare professionals (HCPs) who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Question 8: "How frequently would you offer or recommend FDC SC administration to your patients in the future?" The three available response options were: Always, Sometimes, and Never.

The Healthcare Professional Questionnaire (HCPQ)-Drug Preparation Room Question 1 was completed at each treatment cycle of the Treatment Cross-Over Period by the healthcare professionals (HCPs) within the pharmacy/drug preparation area where pertuzumab IV and trastuzumab IV and pertuzumab and trastuzumab FDC SC were prepared and dispensed for treating the study's participants. HCPs responded to the following question: "How long (in minutes) did it take to prepare the treatment for use?"

Healthcare professionals (HCPs) who prepared study treatment within the pharmacy/drug preparation area responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Drug Preparation Room Question 2: "If all P+H IV infusions are switched to FDC SC injections, please indicate how strongly you agree or disagree with each of the following statements: a) Staff will have increased availability for other tasks in the pharmacy; b) Administrative procedures around FDC SC will require less time; c) FDC SC formulations will provide more flexibility for staff in managing their workload; d) Due to ready-to-use FDC SC formulations, potential dosing errors will be avoided; e) Due to ready-to-use FDC SC formulations, there will be less drug wastage; f) Without having to reconstitute the drug, less storage space for FDC SC related supplies will be required in the pharmacy; g) Preparation procedures and associated time staff time commitment will be reduced."

Healthcare professionals (HCPs) who prepared study treatment within the pharmacy/drug preparation area responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Drug Preparation Room Questions 3 and 4: "Looking back over the Perjeta-Herceptin treatment sessions, please indicate based on your opinion which administration method: Q3. Was quickest from start to end of preparation to finish of administration (excluding observation period)?; Q4. Required less resource use for preparation and administration, for example nursing time, facility costs, equipment etc?" The three available response options were: P+H IV, FDC SC, and No Difference.

The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.

Investigators used the NCI CTCAE v4.0 grading scale for assessing adverse event (AE) severity; if not listed, AE severity was graded as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life-threatening; Grade 5 = death related to AE. Severity and seriousness are not synonymous and investigators independently assessed these criteria for each AE. Investigators also determined whether an AE was considered to be related to the study drug. Adverse events to monitor were defined based on known risks associated with the study drugs and included: hypersensitivity reactions, administration-related reactions (ARRs), cardiac dysfunction, diarrhea grade ≥3, rash/skin reactions, mucositis, interstitial lung disease (ILD), (febrile) neutropenia, pulmonary events that may occur as a result of an ARR, and pregnancy/neonatal related. Multiple occurrences of AEs were counted only once per participant. LVEF = left ventricular ejection fraction

Heart failure is defined as a disorder characterized by the inability of the heart to pump blood at an adequate volume to meet tissue metabolic requirements, or, the ability to do only at an elevation in the filling pressure. Any adverse event of symptomatic left ventricular systolic dysfunction (LVSD; also referred to as heart failure) occurring during the study was to be reported as a serious adverse event.

Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. All participants who enrolled in this study must have had a baseline LVEF ≥55%. Verbatim description of adverse events was mapped to Medical Dictionary for Regulatory Activities (MedDRA) version 25.1. The MedDRA preferred term of 'ejection fraction decreased' is defined as an LVEF decrease of at least 10 percentage points from baseline and to below 50%.

The number of participants at any post-baseline timepoint with abnormal readings outside the normal range for vital signs of diastolic and systolic blood pressure, pulse rate, respiratory rate, and body temperature were summarized according the specified direction of the abnormal reading (high or low). The number analyzed (denominator) in the results table represents participants without the specified abnormal vital sign at baseline. Not every vital sign abnormality qualified as an adverse event (AE). A vital sign result must have been reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption, or treatment discontinuation); resulted in a medical intervention or a change in concomitant therapy; or, was clinically significant in the investigator's judgment.

Laboratory data for targeted chemistry and hematology parameters were classified according to the NCI CTCAE v4.0; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). The results show the shifts in the number of participants with Grade 0-2 at baseline to Grade 3-4 post-baseline; those with missing baseline values were counted as Grade 0-2 at baseline. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption, or treatment discontinuation); resulted in a medical intervention or a change in concomitant therapy; or, was clinically significant in the investigator's judgment. SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase

Overall survival (OS) is defined as the time from randomization to death due to any cause. The number of participants who had an OS event (i.e., died) while on study is reported.

Overall survival is defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization +1 day. Kaplan-Meier methodology was used to estimate the percentage of participants who were alive (event-free) at 12, 24, and 36 months.

Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Second primary non-breast invasive cancer (with the exception of non-melanoma skin cancers and in situ carcinoma of any site) was included as an event.

Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Second primary non-breast invasive cancer (with the exception of non-melanoma skin cancers and in situ carcinoma of any site) was included as an event. Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.

Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) were not counted as recurrence.

Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) were not counted as recurrence. Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.

Distant disease-free survival (DDFS) is defined as the time from randomization to the date of distant breast cancer recurrence (i.e., evidence of breast cancer in any anatomic site other than for ipsilateral \[loco-regional\] invasive breast cancer recurrence that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer).

Distant disease-free survival (DDFS) is defined as the time from randomization to the date of distant breast cancer recurrence (i.e., evidence of breast cancer in any anatomic site other than for ipsilateral \[loco-regional\] invasive breast cancer recurrence that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer). Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.

Hoffmann-La Roche

After initiation of study treatment, all adverse events (AEs) regardless of relationship to study drug were to be reported until 28 days after the last dose of study drug. In the Follow-Up Period, the following AEs were to be reported: study drug-related serious AEs; AEs of special interest, heart failure, pregnancies, non-breast-related second primary malignancies and deaths, irrespective of causal relationship.

This safety analysis population includes all participants from Arms A and B who received up to 3 cycles (1 cycle = 21 days) of treatment with pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Cross-Over Period of the study.

P+H IV: Treatment Cross-Over Period

This safety analysis population includes all participants from Arms A and B who received up to 3 cycles (1 cycle = 21 days) of treatment with the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) during the Treatment Cross-Over Period of the study.

PH FDC SC: Treatment Cross-Over Period

This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive pertuzumab IV and trastuzumab IV (P+H IV) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).

P+H IV: Treatment Continuation Period

This safety analysis population includes all participants from Arms A and B who, following completion of the Treatment Cross-Over Period, chose to receive the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) during the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).

PH FDC SC: Treatment Continuation Period

This safety analysis population includes all participants from Arms A and B who received at least one dose of treatment with pertuzumab IV and trastuzumab IV (P+H IV) and/or the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) across any of the treatment periods during the study from first dose through 28 days after the last dose of study treatment.

All Participants: All Study Treatment Periods

This safety analysis population includes all participants from Arms A and B who had received at least one dose of any study treatment and had not discontinued from the study prior to entering the follow-up period. The timeframe of the follow-up period started at 29 days after the last dose of study treatment until the end of follow-up (≥3 years after randomization of the last participant).

Follow-Up Period

A: P+H IV Followed by PH FDC SC

B: PH FDC SC Followed by P+H IV

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Baseline Weight

ECOG Performance Status: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework or office work.

Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline

Number of Cycles of Prior Neoadjuvant Pertuzumab IV and Trastuzumab IV

Participants were stratified at randomization according to prior neoadjuvant chemotherapy regimen, pathological complete response to prior neoadjuvant treatment, and hormone receptor status.

Prior Neoadjuvant Chemotherapy Regimen

Pathological Complete Response (pCR) to Prior Neoadjuvant Treatment

Hormone Receptor Status

Intent-to-Treat (ITT) Population: includes all randomized participants, allocated to their randomized treatment arm, whether or not the assigned study treatment was received.

Medical Communications

SC Preference

IV Preference

No Preference

In the Treatment Cross-Over Period of the study, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.

All Participants

Modified Intent-to-Treat (mITT) Population: All randomized participants, allocated to their randomized treatment arm, who received at least one dose by both SC and IV routes of administration during the Treatment Cross-over Period and subsequently answered at least Question 1 of the PPQ.

Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ)

SC Preference: Very Strong

SC Preference: Fairly Strong

SC Preference: Not Very Strong

IV Preference: Very Strong

IV Preference: Fairly Strong

IV Preference: Not Very Strong

Modified ITT (mITT) Population; for Question 2 of the PPQ, the number analyzed for the strength of SC or IV preference represents the participants who indicated in their responses to Question 1 of the PPQ that they preferred the SC or IV route of administration, respectively.

Percentage of Participants by Responses to the Strength of Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 2 of the Patient Preference Questionnaire (PPQ)

SC Preference: Feels Less Emotionally Distressing

SC Preference: Requires Less Time in the Clinic

SC Preference: Lower Level of Injection-Site Pain

SC Preference: Feels More Comfortable During Administration

SC Preference: Other Reason

IV Preference: Feels Less Emotionally Distressing

IV Preference: Requires Less Time in the Clinic

IV Preference: Lower Level of Injection-Site Pain

IV Preference: Feels More Comfortable During Administration

IV Preference: Other Reason

Modified ITT (mITT) Population; for Question 3, the number analyzed for the two main reasons for SC or IV preference represents the participants who indicated in their responses to Question 1 of the PPQ that they preferred the SC or IV route of administration, respectively.

Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ)

Very Satisfied

Satisfied

Neither Satisfied nor Dissatisfied

Dissatisfied

Very Dissatisfied

Did Not Answer Question

This analysis set includes all participants from Arms A and B who completed the TASQ-IV questionnaire, which was administered at the last IV treatment cycle in the Treatment Cross-Over Period of the study. During the Treatment Cross-Over Period, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.

All Participants: TASQ-IV Completers

This analysis set includes all participants from Arms A and B who completed the TASQ-SC questionnaire, which was administered at the last SC treatment cycle in the Treatment Cross-Over Period of the study. During the Treatment Cross-Over Period, all participants received their first 6 cycles of treatment in accordance with the study arm to which they were randomized: Arm A) pertuzumab IV and trastuzumab IV (P+H IV) for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days); or Arm B) PH FDC SC for 3 treatment cycles followed by P+H IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.

All Participants: TASQ-SC Completers

Modified Intent-to-Treat (mITT) Population

Percentage of Participants by Their Level of Satisfaction With the Respective Methods of Administration (IV and SC), Question 1 of the Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) and -Subcutaneous (TASQ-SC)

Satisfaction Domain

Physical Impact Domain

Psychological Impact Domain

Impact on Activities of Daily Living Domain

Convenience Domain

Modified Intent-to-Treat (mITT) Population; The number analyzed indicates the number of participants who completed the TASQ-IV/-SC questionnaire items within a domain.

Mean Scores of the Five Domains of the TASQ-IV and TASQ-SC (Satisfaction, Physical Impact, Psychological Impact, Impact on Activities of Daily Living, and Convenience) to Assess the Impact of IV and SC Routes of Administration

a) Yes, I had enough time to talk to my nurse and/or doctor

b) Yes, but I would have liked more time to talk to my nurse and/or doctor

c) It does not matter to me if I have time to talk to my nurse and/or doctor

d) No, I did not have enough time to talk to my nurse and/or doctor

e) No, I did not talk to my nurse and/or doctor at all

Patient did not answer question

Percentage of Participants by Their Responses to Question 9 of the TASQ-IV and TASQ-SC, Assessing Whether Participants Receiving IV and SC Administration Have as Much Time as They Would Like to Talk to Their Nurse and/or Doctor About Their Illness

Patient Did Not Answer Question

Percentage of Participants by Their Responses to Question 10 of the TASQ-IV and TASQ-SC, Assessing Whether IV and SC Administration Have an Impact on the Amount of Time Participants Have to Talk to Their Nurse and/or Doctor About Their Illness

Prefer IV Method

Prefer SC Method

Percentage of Participants by Their Responses to Question 11 of the TASQ-IV and TASQ-SC, Assessing the Participants' Preferred Method for Receiving Cancer Treatment

Chose PH FDC SC for Treatment Continuation

Chose P+H IV for Treatment Continuation

Preferred SC per the PPQ and Chose PH FDC SC for Continuation

Preferred SC per the PPQ and Chose P+H IV for Continuation

Preferred IV per the PPQ and Chose PH FDC SC for Continuation

Preferred IV per the PPQ and Chose P+H IV for Continuation

No Preference per the PPQ and Chose PH FDC SC for Continuation

No Preference per the PPQ and Chose P+H IV for Continuation

All randomized participants, allocated to their randomized treatment arm.

Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ

Cycle 1. Duration of Central Venous Catheter Set Up (IV Only)?

Cycle 1. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?

Cycle 1. Duration of Peripheral Vein Cannulation Set Up (IV Only)?

Cycle 1. How Long Did it Take to Administer the Treatment?

Cycle 1. How Long Was the Patient in the Treatment Room in Total?

Cycle 2. Duration of Central Venous Catheter Set Up (IV Only)?

Cycle 2. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?

Cycle 2. Duration of Peripheral Vein Cannulation Set Up (IV Only)?

Cycle 2. How Long Did it Take to Administer the Treatment?

Cycle 2. How Long Was the Patient in the Treatment Room in Total?

Cycle 3. Duration of Central Venous Catheter Set Up (IV Only)?

Cycle 3. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?

Cycle 3. Duration of Peripheral Vein Cannulation Set Up (IV Only)?

Cycle 3. How Long Did it Take to Administer the Treatment?

Cycle 3. How Long Was the Patient in the Treatment Room in Total?

Cycle 4. Duration of Central Venous Catheter Set Up (IV Only)?

Cycle 4. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?

Cycle 4. Duration of Peripheral Vein Cannulation Set Up (IV Only)?

Cycle 4. How Long Did it Take to Administer the Treatment?

Cycle 4. How Long Was the Patient in the Treatment Room in Total?

Cycle 5. Duration of Central Venous Catheter Set Up (IV Only)?

Cycle 5. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?

Cycle 5. Duration of Peripheral Vein Cannulation Set Up (IV Only)?

Cycle 5. How Long Did it Take to Administer the Treatment?

Cycle 5. How Long Was the Patient in the Treatment Room in Total?

Cycle 6. Duration of Central Venous Catheter Set Up (IV Only)?

Cycle 6. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)?

Cycle 6. Duration of Peripheral Vein Cannulation Set Up (IV Only)?

Cycle 6. How Long Did it Take to Administer the Treatment?

Cycle 6. How Long Was the Patient in the Treatment Room in Total?

The number analyzed includes HCPs who completed question 1 of the survey per treatment cycle. For the questions related to IV access, the number analyzed only includes HCP responses for participants who required new IV access at a given treatment cycle.

Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room

Statement a): Strongly Disagree

Statement a): Disagree

Statement a): Neutral

Statement a): Agree

Statement a): Strongly Agree

Statement a): Not Applicable

Statement a): Answer Missing

Statement b): Strongly Disagree

Statement b): Disagree

Statement b): Neutral

Statement b): Agree

Statement b): Strongly Agree

Statement b): Not Applicable

Statement b): Answer Missing

The number analyzed includes healthcare professionals (HCPs) who completed any part of the survey at treatment Cycle 6.

Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Participants With HER2-Positive Early Breast Cancer	NCT03674112	HER2-Positive E...	Pertuzumab and ... Pertuzumab IV Trastuzumab IV	18 Years -	Hoffmann-La Roche
Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Trastuzumab in HER2+ Breast Cancer Patients	NCT03144947	Cancer, Breast	Trastuzumab IV Trastuzumab SC Pertuzumab Docetaxel	18 Years -	Gruppo Oncologico Italiano di Ricerca Clinica
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	NCT05415215	Early Breast Ca... Locally Advance... Inflammatory Br...	Fixed Dose Comb... Pertuzumab IV Trastuzumab IV Trastuzumab Emt... Investigator's ... Surgery Radiotherapy	18 Years -	Hoffmann-La Roche
A Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Participants With HER2-Positive Early Breast Cancer	NCT03493854	Early Breast Ca...	Cyclophosphamid... Doxorubicin Docetaxel Paclitaxel Pertuzumab IV FDC of Pertuzum... Trastuzumab IV Trastuzumab SC Surgery Post-operative ... Hormone Therapy	18 Years -	Hoffmann-La Roche
A Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Participants With HER2-Positive Early Breast Cancer	NCT03493854	Early Breast Ca...	Cyclophosphamid... Doxorubicin Docetaxel Paclitaxel Pertuzumab IV FDC of Pertuzum... Trastuzumab IV Trastuzumab SC Surgery Post-operative ... Hormone Therapy	18 Years -	Hoffmann-La Roche
A Two-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Chinese Participants With HER2-Positive Early Breast Cancer	NCT04024462	HER2-positive E...	Pertuzumab IV Trastuzumab IV Pertuzumab and ... Doxorubicin Cyclophosphamid... Docetaxel Surgery Post-Operative ... Hormone Therapy	18 Years -	Hoffmann-La Roche

Spots Global Cancer Trial Database for trastuzumab iv