RESUMO
Tres pacientes con cáncer avanzado en tratamiento con inhibidores del punto de control inmunitario (inmune checkpoint inhibitors, ICIs), sin antecedentes de diabetes mellitus (DM), ingresaron al Servicio de Urgencias con poliuria, polidipsia y pérdida de peso, y diagnóstico de cetoacidosis diabética, sin evidencia clínica de infección. Fueron tratados con líquidos e infusión de insulina pasando luego a un régimen de insulina bolo basal que continuó después del alta. Las pruebas de detección de autoanticuerpos para DM resultaron negativas, y se les diagnosticó DM inducida por ICIs, pembrolizumab en dos de ellos y nivolumab en el otro. El propósito de esta serie de casos es demostrar el desarrollo de la DM1 en forma aguda en pacientes tratados con inhibidores de PD-1. Sobre la base de estos casos y la literatura revisada, se buscaron determinar las características clínicas, y sugerir estrategias para la identificación, control, tratamiento precoz y seguimiento de los pacientes tratados con ICIs a fin de minimizar el impacto de la disfunción autoinmune.
Three patients with advanced cancer, treated with inmune checkpoint inhibitors (ICIs), with no history of diabetes mellitus (DM), were admitted to the Emergency Department with polyuria, polydipsia, and weight loss and a diagnosis of diabetic ketoacidosis without clinical evidence of infection. They were treated with fluids and insulin infusion transitioning to a basal-bolus insulin regimen, which continued after discharge. Autoantibody detection tests for DM were negative and they were diagnosed with DM induced by ICIs, pembrolizumab in two of them, and nivolumab in another. The purpose of this case report is to show the development of DM1 in an acute form in patients treated with PD-1 inhibitors. Based on these cases and the reviewed literature, we seek to identify clinical characteristics and suggest strategies for the proper identification, control, treatment, and follow-up of patients treated with ICIs to minimize the impact of autoimmune dysfunction.
Assuntos
ImunoterapiaRESUMO
BACKGROUND: Novel targeted agents and combinations have become available in multiple lines of treatment for human epidermal growth factor receptor 2-positive (HER2(+)) metastatic breast cancer (MBC). In this context, alternatives to the lapatinib (L) and capecitabine (C) regimen, evaluating L combined with other cytotoxic drugs, are warranted. PATIENTS AND METHODS: In the present phase II, multicenter study, patients with HER2(+) MBC with progression after taxane were randomized between L, 1250 mg, combined with C, 2000 mg/m(2) on days 1 to 14 (LC), vinorelbine (V), 25 mg/m(2) on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m(2) on days 1 and 8 (LG), every 21 days. The primary endpoint was the overall response rate. RESULTS: A total of 142 patients were included from 2009 to 2012. No differences were found in the patient baseline characteristics. The median age was 51 years, 69% were postmenopausal, 32% had liver metastasis, 57% were hormone receptor negative, and 48% had been previously treated with trastuzumab. The overall response rate was 49% (95% confidence interval [CI], 34.8%-63.4%), 56% (95% CI, 40%-70.4%), and 41% (95% CI, 27%-56.8%) in the LC, LV, and LG groups, respectively. The median progression-free survival was 9 months in the LC arm and 7 months in the other 2 arms (P = .28). The most common grade 3 and 4 adverse events were hand-foot syndrome (18%), diarrhea (6%), and increased alanine aminotransferase/aspartate aminotransferase (4%) in the LC arm; neutropenia (36%), diarrhea (9%), and febrile neutropenia (6%) in the LV arm; and neutropenia (47%), alanine aminotransferase/aspartate aminotransferase (13%), and rash (4%) in the LG arm. CONCLUSION: LV and LG seem to be active combinations in patients with HER2(+) MBC after taxane failure. The overall toxicity was manageable in all regimens.