Portal de investigación
Efficacy of osimertinib plus bevacizumab in glioblastoma patients with simultaneous EGFR amplification and EGFRvIII mutation
Fecha de publicación:
Fecha Ahead of Print:
Autores organización
Autores
- Jaramillo-Velásquez D
- Ruiz-Patiño A
- Polo C
- Jiménez E
- Hakim F
- Gómez D
- Ramón JF
- Cifuentes H
- Mejía JA
- Salguero F
- Ordoñez C
- Muñoz Á
- Bermúdez S
- Useche N
- Pineda D
- Ricaurte L
- Zatarain-Barrón ZL
- Rodríguez J
- Avila J
- Jaller E
- Sotelo C
- Garcia-Robledo JE
- Santoyo N
- Rolfo C
- Rosell R
- Arrieta O
Grupos de investigación
Resumen
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. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Datos de la publicación
- ISSN/ISSNe:
- 0167-594X, 1573-7373
- Tipo:
- Article
- Páginas:
- 353-364
- Enlace a otro recurso:
- www.scopus.com
Journal Of Neuro-Oncology Springer
Citas Recibidas en Web of Science: 13
Citas Recibidas en Scopus: 25
Documentos
- No hay documentos
Filiaciones
Keywords
- Acrylamides; Adult; Aged; Aniline Compounds; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Glioblastoma; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasm Recurrence, Local; Protein Kinase Inhibitors; Retrospective Studies; bevacizumab; epidermal growth factor receptor; osimertinib; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; platelet derived growth factor receptor; scatter factor receptor; somatomedin C receptor; STAT3 protein; temozolomide; acrylamide derivative; aniline derivative; antineoplastic agent; bevacizumab; EGFR protein, human; epidermal growth factor receptor; epidermal growth factor receptor VIII; osimertinib; protein kinase inhibitor; adult; aged; Article; cancer resistance; cancer surgery; clinical article; cohort analysis; controlled study; diarrhea; drug efficacy; drug exposure; drug safety; drug tolerability; EGFR gene; EGFRvIII gene; fatigue; female; follow up; gene amplif
Proyectos asociados
Determinación de la huella transcipcional de mastocitos aislados de pulpa dental humana sana y con signos clínicos de inflamación
Investigador Principal: MARIA ROSA BUENAHORA TOBAR
PCI-2019-10765 . 2020
EFECTO DEL EXTRACTO DE Trametes versicolor SOBRE EL FENOTIPO Y LA FUNCIÓN DE CÉLULAS DENDRÍTICAS HUMANAS CONDICIONADAS CON MEDIOS DE CÉLULAS DE CARCINOMA ORAL
Investigador Principal: ANDRES FELIPE CARDONA MENDOZA
PCI-2019-10805 . 2020
Citar la publicación
Cardona AF,Jaramillo D,Ruiz A,Polo C,Jiménez E,Hakim F,Gómez D,Ramón JF,Cifuentes H,Mejía JA,Salguero F,Ordoñez C,Muñoz Á,Bermúdez S,Useche N,Pineda D,Ricaurte L,Zatarain ZL,Rodríguez J,Avila J,Rojas L,Jaller E,Sotelo C,Garcia JE,Santoyo N,Rolfo C,Rosell R,Arrieta O. Efficacy of osimertinib plus bevacizumab in glioblastoma patients with simultaneous EGFR amplification and EGFRvIII mutation. J Neurooncol. 2021. 154. (3):p. 353-364. IF:4,506. (2).