Vol:.(1234567890) Clinical and Translational Oncology (2019) 21:1364–1373 https://doi.org/10.1007/s12094-019-02066-2 1 3 RESEARCH ARTICLE A comprehensive analysis of factors related to carmustine/ bevacizumab response in recurrent glioblastoma A. F. Cardona 1,2,3  · L. Rojas 4,5  · B. Wills 2,6  · A. Ruiz‑Patiño 2,5  · L. Abril 2  · F. Hakim 3,7  · E. Jiménez 3,7  · N. Useche 3,8  · S. Bermúdez 3,8  · J. A. Mejía 3,7  · J. F. Ramón 3,7  · H. Carranza 1,2  · C. Vargas 1,2  · J. Otero 2  · P. Archila 2  · J. Rodríguez 2  · J. Rodríguez 2  · J. Behaine 3  · D. González 3  · J. Jacobo 3  · H. Cifuentes 9  · O. Feo 9  · P. Penagos 9,10  · D. Pineda 11  · L. Ricaurte 2  · L. E. Pino 12  · C. Vargas 11  · J. C. Marquez 11  · M. I. Mantilla 11  · L. D. Ortiz 13  · C. Balaña 14  · R. Rosell 14  · Z. L. Zatarain‑Barrón 15  · O. Arrieta 15 Received: 3 September 2018 / Accepted: 15 February 2019 / Published online: 23 February 2019 © Federación de Sociedades Españolas de Oncología (FESEO) 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 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). Mean- while, 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 ben- eft from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy. Keywords Glioblastoma · Second-line therapy · Bevacizumab · Molecular expression classifcation Introduction Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults [1]. Despite the best available treatment, the prognosis for patients with recurrent GBM remains dismal, with a median survival of 25–40 weeks [2–4]. Bevacizumab is a humanized anti- body against vascular endothelial growth factor (VEGF) that received accelerated approval by the Food and Drug Administration (FDA, Silver Spring, Maryland, United States) in 2009 for treating recurrent GBM (rGBM) [5, 6]. Despite the prolonged progression-free survival (PFS) and high response rates (RR) following treatment compared Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12094-019-02066-2) contains supplementary material, which is available to authorized users. A. F. Cardona, L. Rojas, B. Wills, A. Ruiz-Patiño and O. Arrieta contributed equally to the study. * A. F. Cardona a_cardonaz@yahoo.com Extended author information available on the last page of the article