A Study Evaluating Trastuzumab Emtansine Plus Pertuzumab Compared With Chemotherapy Plus Trastuzumab and Pertuzumab for Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

Roche

Status and phase: Completed; Phase 3

Conditions: Breast Neoplasms

Treatments: Drug: Carboplatin; Drug: Pertuzumab; Drug: Trastuzumab Emtansine; Drug: Docetaxel; Drug: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02131064

2012-004879-38 (EudraCT Number)

TRIO021 (Other Identifier)

BO28408

Details and patient eligibility

About

This is a randomized, multicenter, open-label, two-arm study in treatment-naive participants with operable, locally advanced, or inflammatory, centrally-assessed HER2-positive early breast cancer (EBC) whose primary tumors were greater than or equal to (>/=) 2 centimeters (cm). The study was designed to evaluate the efficacy and safety of trastuzumab emtansine + pertuzumab (experimental arm; T-DM1 + P) versus chemotherapy, trastuzumab + pertuzumab (control arm; TCH + P). The study comprised a neoadjuvant treatment period, followed by surgery, and an adjuvant treatment period.

Treatment can be stopped due to disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination.

Enrollment: 444 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed invasive breast cancer with a primary tumor size of greater than (>) 2 cm
• HER2-positive breast cancer
• Participants with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) are eligible provided all discrete lesions are sampled and centrally confirmed as HER2 positive
• Stage at presentation: cT2-cT4, cN0-cN3, cM0, according to American Joint Committee on Cancer (AJCC) staging system
• Known hormone receptor status of the primary tumor
• Participant agreement to undergo mastectomy or breast-conserving surgery after neoadjuvant therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Baseline Left Ventricular Ejection Fraction (LVEF) >/= 55 percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA)
• Effective contraception as defined by protocol

Exclusion criteria

• Stage IV (metastatic) breast cancer
• Participants who have received prior anti-cancer therapy for breast cancer except those participants with a history of breast lobular carcinoma in situ (LCIS) that was surgically managed or ductal carcinoma in situ (DCIS) treated exclusively with mastectomy. In case of prior history of LCIS/DCIS, >5 years must have passed from surgery until diagnosis of current breast cancer
• Participants with multicentric (multiple tumors involving more than 1 quadrant) or bilateral breast cancer
• Participants who have undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
• Axillary lymph node dissection or positive sentinel lymph node prior to start of neoadjuvant therapy
• History of concurrent or previously non-breast malignancies except for appropriately treated (1) non-melanoma skin cancer and (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 >/= 5 years
• Treatment with any investigational drug within 28 days prior to randomization
• Current National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0
• Any significant concurrent medical or surgical conditions or findings that would jeopardize the participant's safety or ability to complete the study
• Current pregnancy or breastfeeding

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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444 participants in 2 patient groups

Trastuzumab (TCH) + Pertuzumab

Active Comparator group

Description:

Participants will receive pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion followed by trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion followed by docetaxel 75 milligrams per square meter (mg/m\^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter\* minute (mg/mL\*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).

Treatment:

Drug: Docetaxel

Drug: Trastuzumab

Drug: Pertuzumab

Drug: Carboplatin

Trastuzumab Emtansine (T-DM1) + Pertuzumab

Experimental group

Description:

Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).

Treatment:

Drug: Trastuzumab Emtansine

Drug: Pertuzumab