Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Bone Density Conservation Agents

Anti-Infective Agents

Trastuzumab

Cyclophosphamide

Tamoxifen

Doxorubicin

Liposomal doxorubicin

Hormones

Docetaxel

Aromatase Inhibitors

Taxane

Pertuzumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Hormone Antagonists

Participants will receive 8 cycles of neoadjuvant chemotherapy: 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab will be given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants will undergo surgery. Thereafter, participants will receive an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.

Participants will receive 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) will be given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants will undergo surgery. Thereafter, participants will receive an additional 14 cycles of the PH FDC SC for a total of 18 cycles.

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

Pertuzumab IV

Trastuzumab will be administered as an 8-milligram per kilogram of body weight (mg/kg) IV loading dose and then 6 mg/kg IV maintenance dose Q3W.

Trastuzumab IV

The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) will be administered SC at a fixed non-weight-based dose. A loading dose of 1200 mg SC pertuzumab and 600 mg SC trastuzumab is then followed by a maintenance dose of 600 mg SC pertuzumab and 600 mg SC trastuzumab Q3W.

Pertuzumab and Trastuzumab FDC SC

Doxorubicin 60 milligrams per meter squared of body surface area (mg/m\^2) will be administered IV on Day 1 of each cycle of treatment (as part of AC Q3W) for Cycles 1-4.

Cyclophosphamide 600 mg/m\^2 will be administered IV on Day 1 of each cycle of treatment (as part of AC Q3W) for Cycles 1-4.

Docetaxel 75 mg/m\^2 will be administered IV on Day 1 of Cycle 5. At the investigator's discretion the dose may be escalated to 100 mg/m\^2 IV for Cycles 6-8 (Q3W) provided no dose-limiting toxicity occurs.

Participants in both cohorts are scheduled to undergo surgery after 8 cycles of neoadjuvant therapy. Participants may undergo breast-conserving surgery or mastectomy according to routine clinical practice.

Surgery

If indicated, radiotherapy is given after chemotherapy and surgery, during adjuvant HER2-targeted therapy and hormone therapy (for hormone-receptor positive disease).

Post-Operative Radiotherapy

For hormone receptor positive breast cancer, tamoxifen or aromatase inhibitors will be allowed as adjuvant hormone therapy for postmenopausal participants and with ovarian suppression or ablation for premenopausal participants in countries where it has been registered for this indication. Its use must be consistent with the registered label. Hormone therapy is given after chemotherapy and surgery during adjuvant HER2-targeted therapy.

Hormone Therapy

Clinical Trials

This study will evaluate the pharmacokinetics, efficacy, and safety of the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) as compared with those of the pertuzumab intravenous (IV) and trastuzumab IV formulations in Chinese participants with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer.

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

A Phase III, Randomized, Multicenter, Open-Label, 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 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 Sharing of Clinical Study 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).

The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a Cycle 7 subcutaneous injection site other than thigh was used, if the Cycle 8 IV pre-dose and post-dose PK samples were switched, and an assay error impacting Ctrough measurement.

The observed trastuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a Cycle 7 subcutaneous injection site other than thigh was used, if the Cycle 8 IV pre-dose and post-dose PK samples were switched, and an assay error impacting Ctrough measurement.

Total pathological complete response (tpCR) was defined as eradication of invasive disease in the breast and axilla; that is, ypT0/is ypN0, according to the local pathologists' assessment. Pathologic response to therapy was determined at the time of surgery. The tpCR rate is the percentage of participants in the ITT population who achieved a tpCR. Participants with missing data for tpCR (i.e., do not undergo surgery or have an invalid pCR assessment) were included in the analysis and classified as non-responders. Rates of tpCR were calculated in each treatment arm and were assessed using the difference between the Arm B: Pertuzumab and Trastuzumab FDC SC and the Arm A: Pertuzumab IV and Trastuzumab IV tpCR rates and corresponding 95% Clopper-Pearson confidence intervals (CIs). The difference between the tpCR rates along with corresponding 95% Hauck-Anderson CIs were calculated.

iDFS (excluding SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.

iDFS including SPNBC is defined in the same way as iDFS but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).

EFS (excluding SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.

EFS including SPNBC is defined in the same way as EFS, but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).

DRFI is defined as the time between randomization and the date of distant breast cancer recurrence.

A primary cardiac event is defined as either a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III/IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%, or a definite or probable cardiac death. NYHA Class III is defined as: marked limitation of physical activity; comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. NYHA Class IV is defined as: Inability to carry on any physical activity without discomfort; symptoms of cardiac insufficiency at rest; if any physical activity is undertaken, discomfort is increased. Definite cardiac death is defined as death due to heart failure, myocardial infarction, or documented primary arrhythmia. Probable cardiac death is defined as sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, etc.) without documented etiology.

An LVSD ("Ejection fraction decreased") of NYHA Class II is defined as a left ventricular ejection fraction (LVEF) decrease of ≥10-percentage points below the baseline measurement to an absolute LVEF value of \<50%, confirmed by a second LVEF assessment within approximately 3 weeks also showing a documented drop.

Hoffmann-La Roche

Adverse events (AEs) were analyzed for the safety analysis population, which included all participants who received at least one dose of study medication, according to the treatment actually received. One participant randomized to Arm A (IV) mistakenly received 1 SC injection of pertuzumab and trastuzumab FDC SC and was counted in Arm B (SC) for safety; total number analyzed in Arm A: 101-1=100, Arm B: 99+1=100. AEs are still being collected and will be updated within 1 year of study completion.

Participants received 8 cycles of neoadjuvant chemotherapy: 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy

Participants received 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) were given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the PH FDC SC for a total of 18 cycles.

Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Hormone receptor status was based on central assessment of participant samples for estrogen receptor (ER) and progesterone receptor (PgR) negativity or positivity.

Randomization Stratification Factors: Hormone Receptor Status

Breast cancer stages range from 0 to IV with IV being the most advanced stage, which is considered a worse outcome. Stages II and III are both invasive breast cancer stages and are subdivided into IIA, IIB, IIIA, IIIB and IIIC based on tumor size, presence and number of metastases in regional lymph nodes and presence of distant metastases. Participants enrolling in this study were categorized into stages II-IIIA and IIIB-IIIC with IIIC being considered the worst stage.

Randomization Stratification Factors: Clinical Stage at Presentation

Medical Communications

The null hypothesis was that the pertuzumab Arm B SC dose is inferior to the pertuzumab Arm A IV dose (i.e., the CtroughSC/CtroughIV geometric mean ratio of the SC dose of pertuzumab relative to the IV dose is not greater than 0.8).

Pertuzumab Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments.

Serum Trough Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8)

The null hypothesis was that the trastuzumab Arm B SC dose is inferior to the Arm A trastuzumab IV dose (i.e., the CtroughSC/CtroughIV geometric mean ratio of the SC dose of trastuzumab relative to the IV dose is not greater than 0.8).

Trastuzumab Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments.

Serum Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8)

ITT Population: includes all enrolled participants.

Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria

Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival

Number of Participants With at Least One Adverse Event by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 (NCI CTCAE v4)

Number of Participants With a Primary Cardiac Event

Number of Participants With a Secondary Cardiac Event, Defined as an Asymptomatic or Mildly Symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II

Spots Global Cancer Trial Database for pertuzumab and trastuzumab fdc sc