neoadjuvant tdm1 with lapatinib and abraxane compared with trastuzumab plus pertuzumab with paclitaxel

Conditions: Breast Cancer

Summary: this is a randomized, open label phase ii neoadjuvant study comparing the efficacy and safety of trastuzumab emtansine (t-dm1) plus lapatinib (l)followed by abraxane (a) versus trastuzumab plus pertuzumab followed by paclitaxel in patients with her2-overexpressing breast cancer.

this is a randomized, open label phase ii neoadjuvant study comparing the efficacy and safety of trastuzumab emtansine (t-dm1) plus lapatinib (l) followed by abraxane (a) versus trastuzumab plus pertuzumab followed by paclitaxel in patients with her2-overexpressing breast cancer. patients will be randomized (1:1) to one of the two treatment arms: arm 1, trastuzumab emtansine plus lapatinib for 6 weeks, followed by trastuzumab emtansine plus lapatinib plus abraxane for 12 weeks; arm 2, trastuzumab plus pertuzumab for six weeks, followed by trastuzumab plus pertuzumab plus paclitaxel for 12 weeks. patients will undergo surgery after neoadjuvant therapy. all patients will have a core needle biopsy at baseline, after week 6, and at the time of disease progression. surgical specimens will be obtained after week 18.

Eligibility criteria:
inclusion criteria: * female gender; * age ≥18 years; * performance status- eastern cooperative oncology group (ecog) 0-1 * histologically confirmed invasive breast cancer: * primary tumor greater than 1 cm diameter, measured by clinical examination and mammography or ultrasound. * any n, * no evidence of metastasis (m0) (isolated supra-clavicular node involvement allowed); * over expression and/or amplification of her2 in the invasive component of the primary tumor and confirmed by a certified laboratory prior to randomization. * known hormone receptor status. * hematopoietic status: * cbc not less than .75 of institutional lower limit. absolute neutrophil count ≥ 1,5 x 10\^9/l, platelet count ≥ 100 x 10\^9/l, hemoglobin at least 9 g/dl, * hepatic status: serum total bilirubin ≤ 2 x upper limit of normal (uln). in the case of known gilbert's syndrome, a higher serum total bilirubin (\< 1.5 x uln) is allowed, aspartate aminotransferase (ast) and alanine aminotransferase (alt) ≤ 3.5 times uln, alkaline phosphatase ≤ 2.5 times uln, • renal status: creatinine ≤ 1.5mg/dl, • cardiovascular: baseline left ventricular ejection fraction (lvef) ³ ≥50% measured by echocardiography (echo) or multiple gate acquisition (muga) scan, * negative serum or urine β-hcg pregnancy test at screening for patients of childbearing potential within 2-weeks (preferably 7 days) prior to randomization. * fertile patients must use effective contraception (barrier method - condoms, diaphragm - also in conjunction with spermicidal jelly, or total abstinence. oral, injectable, or implant hormonal contraceptives are not allowed) * signed informed consent form (icf) * patient accepts to make available tumor samples for submission to central laboratory to conduct translational studies as part of this protocol. exclusion criteria: * previous (less than 5 years) or current history of malignant neoplasms, except for curatively treated: basal and squamous cell carcinoma of the skin; carcinoma in situ of the cervix. * patients with a prior malignancy diagnosed more than 5 years prior to randomization may enter the study. * preexisting peripheral neuropathy ≥ grade 2 * known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic therapy with oxygen; * concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety; * unresolved or unstable, serious adverse events from prior administration of another investigational drug; * dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of icf; * malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. subjects with ulcerative colitis are also excluded; * concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies); * concurrent treatment with an investigational agent or participation in another therapeutic clinical trial; * known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab emtansine, trastuzumab, lapatinib, paclitaxel, abraxane or their components; * pregnant or lactating women; * concomitant use of cyp3a4 inhibitors or inducers * other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol * patients have an active infection and require iv or oral antibiotics. * pregnant or breast-feeding women * patients unwilling or unable to comply with the protocol

Keywords: neoadjuvant breast cancer her2 positive breast cancer