a study to evaluate the efficacy and safety of atezolizumab or placebo in combination with neoadjuvant doxorubicin + cyclophosphamide followed by paclitaxel + trastuzumab + pertuzumab in early her2-positive breast cancer

Conditions: Breast Cancer

Summary: this study (also known as impassion050) will evaluate the efficacy and safety of atezolizumab compared with placebo when given in combination with neoadjuvant dose-dense anthracycline (doxorubicin) + cyclophosphamide followed by paclitaxel + trastuzumab + pertuzumab (ddac-pachp) in patients with early her2-positive breast cancer (t2-4, n1-3, m0).


Eligibility criteria:
inclusion criteria: * confirmed diagnosis of her2-positive breast cancer, and hormonal and pd-l1 status, as documented through central testing of a representative tumor tissue specimen * primary breast tumor size of \> 2 cm by any radiographic measurement * stage at presentation: t2-t4, n1-n3, m0 as determined by ajcc staging system, 8th edition * pathologic confirmation of nodal involvement with malignancy must be determined by fine needle aspiration or core-needle biopsy. surgical excision of lymph nodes is not permitted. * patients with multifocal tumors are eligible provided at least one focus is sampled and centrally confirmed as her2-positive. * patients with multicentric tumors are eligible provided all discrete lesions are sampled and centrally confirmed as her2-positive. * eastern cooperative oncology group performance status of 0 or 1 * baseline lvef \>= 55% measured by echocardiogram (echo) or multiple-gated acquisition (muga) scans * adequate hematologic and end-organ function obtained within 14 days prior to initiation of study treatment * for women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs * for men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm exclusion criteria: * prior history of invasive breast cancer * stage iv (metastatic) breast cancer * patients with synchronous bilateral invasive breast cancer * prior systemic therapy for treatment of breast cancer * previous therapy with anthracyclines or taxanes for any malignancy * ulcerating or inflammatory breast cancer * undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes * sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy * history of other malignancy within 5 years prior to screening, with the exception of those patients who have a negligible risk of metastasis or death * cardiopulmonary dysfunction * dyspnea at rest * active or history of autoimmune disease or immune deficiency * pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab/placebo, 6 months after the final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after the final dose of paclitaxel, or 7 months after the final dose of trastuzumab, pertuzumab, or trastuzumab emtansine whichever occurs last exclusion criteria related to trastuzumab emtansine in the adjuvant setting: * patients who achieved pcr * evidence of clinically evident gross residual or recurrent disease following neoadjuvant therapy and surgery * unable to complete surgery with curative intent after conclusion of neoadjuvant systemic therapy * patient discontinued treatment with trastuzumab because of toxicity during the neoadjuvant phase of the study * clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, or sclerosis cholangitis * patients with grade \>=2 peripheral neuropathy * prior treatment with trastuzumab emtansine