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

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Rojas, Leonardo
Wills, Beatriz
Ruiz Patiño, Alejandro
Abril, Lina Alejandra
Jiménez, Encarnación
Useche, Nicolás
Bermúdez, Sonia
Mejia, Juan Alberto
Ramón, Juan Fernando
Carranza, 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
Published in
Clinical and Translational Oncology, 1699-048X, Vol. 21, 2019, p.1364-1373
Published for
Springer
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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 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.
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