A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma

Purpose Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efcacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. Methods/patients In this study, we assessed 59 adult patients with histologically confrmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profle, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplifcation, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. Results Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0–9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2–28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5–11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively afected PFS included performance status (p=0.015), IDH+ (p=0.05), CD133 mRNA expression (p=0.009) and pMGMT+ (p=0.007). OS was positively afected by pMGMT+ (p=0.05). Meanwhile, YKL40 negatively afected PFS (p=0.01) and OS (p=0.0001). Grade≥3 toxicities included hypertension (22%) and fatigue (12%). Conclusions BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest beneft from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.

• Autores: Cardona-Mendoza, Andrés Felipe; Rojas Puentes, Leonardo; Wills, Beatriz; Ruíz-Patiño, Alejandro; Abril, Lina Alejandra; Jiménez, Encarnación; Useche, Nicolás; Bermúdez, Sonia; Mejia, Juan Alberto; Ramón, Juan Fernando; Carranza Isaza, Hernán; Vargas, César; Otero, Jorge; Archila, Pilar; Rodríguez, Jaime; Behaine, José; González, Daniel; Jacobo, Juan; Cifuentes, Héctor; Feo, Oscar; Penagos, Pedro; Pineda, David; Ricaurte, Luisa María; Pino, Luis Eduardo; Vargas, Carlos Andrés; Márquez, Joana; Mantilla, Monica; Ortiz, Leon D.; Balaña, Carme; Rosell, Rafael; Zatarain-Barrón, Zyanya Lucia; Arrieta, Oscar; Hakim, Fernando
• Fecha de publicación: 2019
• Institución: Universidad El Bosque
• Repositorio: Repositorio U. El Bosque
• Idioma: eng
• OAI Identifier: oai:repositorio.unbosque.edu.co:20.500.12495/2018
• Acceso en línea: http://hdl.handle.net/20.500.12495/2018; https://doi.org/10.1007/s12094-019-02066-2
• Palabra clave: Neoplasias neuroepiteliales; Anticuerpos monoclonales; Impresión molecular; Glioblastoma; Second-line therapy; Bevacizumab; Molecular expression classifcation
• License: Acceso cerrado