a study to compare pertuzumab + trastuzumab + vinorelbine vs. placebo + trastuzumab + docetaxel in previously untreated her2-positive metastatic breast cancer

Conditions: Advanced Breast Cancer; HER2-positive Breast Cancer

Summary: this is a randomized, open-label, two-arm, phase iii trial in germany to investigate whether vinorelbine-based triple combination presents a less toxic treatment option than docetaxel-based triple combination in patients with her2-positive advanced breast cancer who have not previously received any systemic treatment in the metastatic setting. the primary objective of the study is to compare patient-reported quality of life in the two treatment arms. patients will be followed-up for survival until death or end of study after at least 79 deaths occured in each arm, whatever comes first.


Eligibility criteria:
inclusion criteria: * signed and dated written informed consent prior to beginning of protocol-specific procedures. * histologically or cytologically confirmed adenocarcinoma of the breast. locally advanced and inoperable or metastatic disease. * her2-positive disease, defined as ihc status her2+++ or cish/fish status positive. * female patients aged ≥ 18 years. * in case of adjuvant treatment, disease-free interval of at least 12 months after completion of adjuvant treatment (excluding hormonal therapy). * eastern cooperative oncology group (ecog) performance status 0-1. * left ventricular ejection fraction (lvef) ≥ 50%. * for women with childbearing potential, defined as physiologically capable of becoming pregnant: * negative pregnancy test. * agreement to use an effective form of contraception during study treatment and for 7 months after the last dose of study treatment. * life expectancy of at least 12 weeks. * adequate organ and bone marrow function * fluent in spoken and written german and willing to answer the questionnaires exclusion criteria: * previous systemic treatment in palliative intention (chemotherapy, hormonal therapy and / or biological therapy) * persistent peripheral sensory or motor neuropathy grade 2 or higher (nci ctcae v5.0) * evidence of central nervous system metastases. ct or mri of the brain is only mandatory in case of clinical suspicion of brain metastases * current uncontrolled hypertension (systolic \> 150 mmhg and / or diastolic \> 100 mmhg) or clinically significant cardiovascular disease * history of lvef \< 50% during or after prior (neo)adjuvant therapy with trastuzumab * current severe, uncontrolled systemic disease (e.g. cardiovascular, pulmonary, or metabolic disease, wound healing disorder, ulcers, or bone fractures, or severe fungal, bacterial or viral infection) * major surgery within 28 days prior to start of study medication, or anticipation of the need for major surgery during the course of study treatment * current known infection with hiv, hbv, or hcv (testing not required) * dyspnea at rest due to complications of advanced malignancy, or other diseases requiring continuous oxygen therapy. * known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies. * participation in investigational studies within 30 days or five half-lives of the respective imp, whichever is longer, prior randomization. * pregnant or lactating women.

Keywords: advanced breast cancer her2-positive metastatic inoperable female quality of life