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01-10-2019 | Glioblastoma | Research Article

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

Authors: A. F. Cardona, L. Rojas, B. Wills, A. Ruiz-Patiño, L. Abril, F. Hakim, E. Jiménez, N. Useche, S. Bermúdez, J. A. Mejía, J. F. Ramón, H. Carranza, C. Vargas, J. Otero, P. Archila, J. Rodríguez, J. Rodríguez, J. Behaine, D. González, J. Jacobo, H. Cifuentes, O. Feo, P. Penagos, D. Pineda, L. Ricaurte, L. E. Pino, C. Vargas, J. C. Marquez, M. I. Mantilla, L. D. Ortiz, C. Balaña, R. Rosell, Z. L. Zatarain-Barrón, O. Arrieta

Published in: Clinical and Translational Oncology | Issue 10/2019

Abstract

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 efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM.

Methods/patients

In this study, we assessed 59 adult patients with histologically confirmed 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 profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, 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 affected 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 affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected 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 benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.

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Title: A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma
Authors: A. F. Cardona
L. Rojas
B. Wills
A. Ruiz-Patiño
L. Abril
F. Hakim
E. Jiménez
N. Useche
S. Bermúdez
J. A. Mejía
J. F. Ramón
H. Carranza
C. Vargas
J. Otero
P. Archila
J. Rodríguez
J. Rodríguez
J. Behaine
D. González
J. Jacobo
H. Cifuentes
O. Feo
P. Penagos
D. Pineda
L. Ricaurte
L. E. Pino
C. Vargas
J. C. Marquez
M. I. Mantilla
L. D. Ortiz
C. Balaña
R. Rosell
Z. L. Zatarain-Barrón
O. Arrieta
Publication date: 01-10-2019
Publisher: Springer International Publishing
Keywords: Glioblastoma
Glioblastoma
Glioblastoma
Bevacizumab
Published in: Clinical and Translational Oncology / Issue 10/2019
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-019-02066-2

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