ABSTRACT
PURPOSE: Intravenous trastuzumab, pertuzumab, and docetaxel are first-line standard of care for patients with HER2-positive metastatic breast cancer (mBC). MetaPHER is the first study assessing the safety and tolerability of subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy in a global patient population with HER2-positive mBC. METHODS: In this open-label, single-arm, multicenter, phase 3b study, eligible patients were ≥ 18 years old with histologically/cytologically confirmed previously untreated HER2-positive mBC. All received ≥ 1 subcutaneous trastuzumab 600 mg fixed dose plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance: 420 mg/kg) and docetaxel (≥ 6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy. RESULTS: At clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia; the most common grade ≥ 3 events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%. CONCLUSIONS: Safety and efficacy with subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in mBC are consistent with historical evidence of intravenous trastuzumab with this combination. Findings further support subcutaneous administration not affecting safety/efficacy profiles of trastuzumab in HER2-positive BC with increased flexibility in patient care. A fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection has recently been approved for the treatment of HER2-positive early/mBC, further addressing the increasing relevance of and need for patient-centric treatment strategies. TRIAL REGISTRATION: NCT02402712.
Subject(s)
Breast Neoplasms , Adolescent , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor , Breast Neoplasms/drug therapy , Docetaxel/therapeutic use , Female , Humans , Receptor, ErbB-2/genetics , Stroke Volume , Trastuzumab/adverse effects , Ventricular Function, LeftABSTRACT
BACKGROUND: In laryngeal cancer, multidisciplinary treatment improves the patient's quality of life and the possibility of preserving the larynx. Most cases occur in a locally advanced stage. The aim is to present the results according to the stage. METHOD: A retrospective study which analyzed the clinical stage, type of primary treatment, outcomes, and survival were analyzed. RESULTS: 451 patients were included. The median age was 66 years. The majority of the tumors presented in advanced stage (72%) and the most affected subsite was the glottis (84.5%). In the early stage the most frequent treatment was radiotherapy as the only treatment modality. In stages III and IVA, 65% were resectable. In stage IVB the management was non-surgical, with control in 26% of the cases. Survival at 10 years was related to the clinical stage: 81.7% for stage I and 0% for stages IVB and IVC. CONCLUSIONS: Patients with laryngeal cancer should be treated according to the clinical stage, through a multidisciplinary approach. Long-term follow-up showed a worse prognosis for advanced clinical stages.
ANTECEDENTES: En cáncer de laringe, el tratamiento multidisciplinario mejora la calidad de vida del paciente y la posibilidad de preservar la laringe. La mayor parte de estos cánceres se presentan localmente avanzados. El objetivo es presentar los resultados de acuerdo con la etapa. MÉTODO: Estudio retrospectivo en el que se analizaron la etapa clínica, el tipo de tratamiento primario, los resultados y la sobrevida. RESULTADOS: Se incluyeron 451 pacientes. La mediana de edad fue de 66 años. El mayor porcentaje de los tumores se presentó en etapa avanzada (72%) y el sitio más afectado fue la glotis (84.5%). En etapa temprana, el tratamiento más frecuente fue la radioterapia. En las etapas III y IVA, el 65% fueron operables. En la etapa IVB el manejo fue no quirúrgico, con control en el 26% de los casos. La supervivencias a 10 años se relacionaron con la etapa clínica: 81.7% para la etapa I y 0% para las etapas IVB y IVC. CONCLUSIONES: Los pacientes con cáncer de laringe deben ser tratados de acuerdo con la etapa clínica y mediante un abordaje multidisciplinario. El seguimiento a largo plazo demostró un peor pronóstico para las etapas clínicas avanzadas.
