ABSTRACT
BACKGROUND: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer. METHODS: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial next-generation sequencing panel in liquid biopsy. RESULTS: There were ten males (66.7%), and the median patient's age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR. CONCLUSIONS: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Glioblastoma , Acrylamides , Adult , Aged , Aniline Compounds , Bevacizumab/therapeutic use , Carcinoma, Non-Small-Cell Lung , ErbB Receptors/genetics , Female , Glioblastoma/drug therapy , Glioblastoma/genetics , Humans , Lung Neoplasms , Male , Middle Aged , Mutation , Neoplasm Recurrence, Local , Protein Kinase Inhibitors , Retrospective StudiesABSTRACT
El artículo describe los lineamientos del sistema propuesto, buscando interesar a los profesionales del área de la salud que confrontan problemas similares a los que CESI pretende responder
Subject(s)
Humans , Epidemiology , Information Systems/instrumentation , Social Planning , BoliviaABSTRACT
El propósito de esta publicación es ofrecer a los gerentes de programas y prestadores de servicios, datos actualizados sobre la situación de indicadores de salud sexual y reproductiva de la población adolescente. Entre los muchos datos interesantes del estudio, resaltan algunos como la edad media del inicio de relaciones sexuales con coito, que se calcula en 15.5 años y la edad media del primer embarazo en 16.7 años. Al momento de la encuesta 33 por ciento de los entrevistados de ambos sexos (14 a 19 años) ya habían tenido relaciones con coito y sólo un 55 por ciento de las mujeres declararon que podrían elegir a su pareja sexual
