ABSTRACT
PURPOSE: This study investigated the safety and clinical activity of lumretuzumab, a humanised antihuman epidermal growth factor receptor 3 (HER3) monoclonal antibody, in combination with carboplatin and paclitaxel in first-line treatment of patients with squamous non-small cell lung cancer (sqNSCLC). HER3 ligand heregulin and HER3 protein expression were evaluated as potential biomarkers of clinical activity. PATIENTS AND METHODS: This open-label, phase Ib/II study enrolled patients receiving lumretuzumab at 800 mg (flat) in combination with carboplatin (area under the curve (AUC) 6 mg/mL×min) and paclitaxel (200 mg/m2) administered intravenously on a every 3-week schedule. Adverse event (AE) rates and tumour responses were determined. Heregulin messenger RNA (mRNA) and HER3 protein expression were investigated in archival tumour biopsies. RESULTS: Altogether, 12 patients received lumretuzumab in combination with carboplatin and paclitaxel. The most frequent AEs were gastrointestinal, haematological and nervous system toxicities, which were generally mild and manageable. Partial responses were observed in 3 of 12 patients lasting 81, 177 and 207 days. All responses were achieved in tumours expressing higher heregulin mRNA levels. CONCLUSION: Lumretuzumab in combination with carboplatin and paclitaxel was well tolerated. Objective responses were enriched in tumours expressing higher heregulin mRNA levels.
ABSTRACT
La neumonía organizada es una entidad clinicohistológica que suele manifestarse de forma subaguda con clínica respiratoria e infiltrados pulmonares. Puede ser de causa desconocida (criptogenética) o estar asociada a distintas enfermedades, infecciones o fármacos. Presentamos el caso de una paciente de 60 años con antecedentes de una neoplasia de mama, motivo por el cual seguía tratamiento con trastuzumab, un anticuerpo monoclonal anti-HER2, a quien se detectó de forma casual un infiltrado pulmonar, cuya biopsia transbronquial fue diagnóstica de neumonía organizada. Tras la retirada del fármaco desapareció el infiltrado pulmonar. Debido a la creciente utilización de la terapia biológica en diferentes campos de la clínica, nos parece de interés comunicar esta forma de afectación pulmonar atribuible al anticuerpo monoclonal trastuzumab(AU)
Organizing pneumonia is a clinical and histological condition in which the onset is usually subacute with respiratory symptoms and pulmonary infiltrates. It may be unknown origin (cryptogenic) or associated with other illnesses, infectious diseases or drugs. We present a 60 year-old female patient with a previous history of breast cancer, who was being treated with trastuzumab, an antiHER2 monoclonal antibody. She was diagnosed with casual pulmonary infiltrates that had histological changes compatible with organizing pneumonia. The pulmonary infiltrates disappeared on withdrawing trastuzumab treatment. Due to the increasing use of biological therapies in different medical areas, we believe it is of interest to report this pulmonary involvement attributed to the monoclonal antibody trastuzumab(AU)
Subject(s)
Humans , Female , Middle Aged , Antibodies, Monoclonal/adverse effects , Pneumonia/chemically induced , Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Biological TherapyABSTRACT
Organizing pneumonia is a clinical and histological condition in which the onset is usually subacute with respiratory symptoms and pulmonary infiltrates. It may be unknown origin (cryptogenic) or associated with other illnesses, infectious diseases or drugs. We present a 60 year-old female patient with a previous history of breast cancer, who was being treated with trastuzumab, an antiHER2 monoclonal antibody. She was diagnosed with casual pulmonary infiltrates that had histological changes compatible with organizing pneumonia. The pulmonary infiltrates disappeared on withdrawing trastuzumab treatment. Due to the increasing use of biological therapies in different medical areas, we believe it is of interest to report this pulmonary involvement attributed to the monoclonal antibody trastuzumab.
