Resumen

Este estudio fue un ensayo clínico internacional, multicéntrico, de fase III, aleatorizado, doble ciego y controlado con placebo, realizado para investigar el uso de pertuzumab en combinación con trastuzumab y docetaxel como tratamiento de primera línea en participantes con cáncer de mama metastásico (CMM) positivo para el receptor 2 del factor de crecimiento epidérmico humano (HER2). Los participantes podían haber recibido un tratamiento hormonal previo para el CMM. Los participantes también podían haber recibido tratamiento sistémico para el cáncer de mama en el entorno neoadyuvante o adyuvante, siempre que hubieran experimentado un intervalo libre de enfermedad (ILE) mayor o igual (≥) a 12 meses desde la finalización del tratamiento sistémico adyuvante (excluyendo la terapia hormonal) hasta el diagnóstico metastásico. Los participantes podían haber recibido trastuzumab o un taxano durante el tratamiento neoadyuvante o adyuvante. Los participantes fueron aleatorizados en proporción 1:1 para recibir pertuzumab o placebo, junto con trastuzumab y docetaxel una vez cada 3 semanas (c3s), durante la fase de tratamiento del estudio, hasta la progresión de la enfermedad (radiográfica o clínica evaluada por el investigador), toxicidad inmanejable o terminación del estudio. No se permitió a los participantes del brazo de placebo recibir pertuzumab de etiqueta abierta tras la interrupción del tratamiento del estudio. No obstante, si algún análisis de supervivencia global cumplía los criterios predefinidos de significación estadística, se ofrecía a los participantes del brazo de placebo que aún estuvieran en tratamiento la opción de recibir pertuzumab de etiqueta abierta además de los demás medicamentos del estudio.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and candidate for chemotherapy. Participants with measurable and non-measurable disease are eligible (locally recurrent disease must not be amenable to resection with curative intent; participants with de novo Stage IV disease are eligible)
Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC)
Left ventricular ejection fraction (LVEF) ≥50 percent (%) at baseline (within 42 days of randomization)
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective form of contraception and to continue its use for the duration of study treatment and for at least 7 months after the last dose of study treatment

Criterios de exclusión

History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC, which must be stopped prior to randomization)
History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting
History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of less than (\<)12 months
History of persistent Grade ≥2 hematologic toxicity resulting from previous adjuvant therapy
Current peripheral neuropathy of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0, Grade ≥3 at randomization
History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent
Current clinical or radiographic evidence of central nervous system (CNS) metastases
Computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain is mandatory in cases of clinical suspicion of brain metastases
History of exposure to cumulative doses of anthracyclines
Current uncontrolled hypertension or unstable angina
History of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception: atrial fibrillation or paroxysmal supraventricular tachycardia)
History of myocardial infarction within 6 months of randomization
History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
Inadequate organ function, as defined in the protocol, within 28 days prior to randomization
Current severe, uncontrolled systemic disease
Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
Pregnant or lactating women
History of receiving any investigational treatment within 28 days of randomization
Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
Receipt of IV antibiotics for infection within 14 days of randomization
Current chronic daily treatment with corticosteroids (excluding inhaled steroids)
Known hypersensitivity to any of the study drugs
Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Intervenciones

drug

Pertuzumab

Pertuzumab was administered as an intravenous (IV) loading dose of 840 milligrams (mg) q3w on Day 1 of Cycle 1 (1 Cycle length = 21 days), and 420 mg q3w on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, unmanageable toxicity, or study termination.

drug

Placebo

Placebo (matching pertuzumab) was administered intravenously.

drug

Trastuzumab

Trastuzumab was administered as an IV loading dose of 8 milligrams per kilogram (mg/kg) q3w on Day 2 of Cycle 1 (1 Cycle length = 21 days), and 6 mg/kg q3w on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, unmanageable toxicity, or study termination.

drug

Docetaxel

Docetaxel was administered as an IV dose of 75 milligrams per square meter of body surface area (mg/m\^2) q3w on Day 2 of Cycle 1 (1 Cycle length = 21 days), and 75 mg/m\^2 (up to 100 mg/m\^2 as per treating physician discretion) q3w on Day 1 of subsequent cycles until investigator-assessed radiographic or clinical progressive disease, unmanageable toxicity, or study termination. On or prior to Cycle 6, docetaxel was only to be discontinued for progressive disease or unmanageable toxicity. After Cycle 6, continuation of docetaxel treatment was at the discretion of the participant and treating physician.

Ubicaciones

Sanatorio Güemes; Oncología

Buenos Aires, Argentina

Centro de Oncologia e Investigacion Buenos Aires (COIBA)

Buenos Aires, Argentina

Instituto Medico Especializado (IME); Oncologia

Caba, Argentina

Center Instituto Médico Privado I.M.P.; Oncology

Chaco-resistencia, Argentina

Policlinica Privada Site la Plata SA; Oncology

La Plata, Argentina

Unidad Oncológica De Neuquén

Neuquén, Argentina

Hosp Provincial D. Centenarios; Oncology Dept

Rosario, Argentina

Ensayo Clínico de Fase III, Aleatorizado, Doble Ciego, Controlado con Placebo, Multicéntrico e Internacional para Evaluar la Eficacia y Seguridad de Pertuzumab + Trastuzumab + Docetaxel versus Placebo + Trastuzumab + Docetaxel en Cáncer de Mama Metastásico HER2-Positivo Sin Tratamiento Previo

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pertuzumab

Placebo

Trastuzumab

Docetaxel

Ubicaciones

Sanatorio Güemes; Oncología

Centro de Oncologia e Investigacion Buenos Aires (COIBA)

Instituto Medico Especializado (IME); Oncologia

Center Instituto Médico Privado I.M.P.; Oncology

Policlinica Privada Site la Plata SA; Oncology

Unidad Oncológica De Neuquén

Hosp Provincial D. Centenarios; Oncology Dept

Patrocinadores