TY - JOUR
T1 - A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma
AU - Cardona, A. F.
AU - Rojas, L.
AU - Wills, B.
AU - Ruiz-Patiño, A.
AU - Abril, L.
AU - Hakim, F.
AU - Jiménez, E.
AU - Useche, N.
AU - Bermúdez, S.
AU - Mejía, J. A.
AU - Ramón, J. F.
AU - Carranza, H.
AU - Vargas, C.
AU - Otero, J.
AU - Archila, P.
AU - Rodríguez, J.
AU - Rodríguez, J.
AU - Behaine, J.
AU - González, D.
AU - Jacobo, J.
AU - Cifuentes, H.
AU - Feo, O.
AU - Penagos, P.
AU - Pineda, D.
AU - Ricaurte, L.
AU - Pino, L. E.
AU - Vargas, C.
AU - Marquez, J. C.
AU - Mantilla, M. I.
AU - Ortiz, L. D.
AU - Balaña, C.
AU - Rosell, R.
AU - Zatarain-Barrón, Z. L.
AU - Arrieta, O.
N1 - Publisher Copyright:
© 2019, Federación de Sociedades Españolas de Oncología (FESEO).
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - Bevacizumab
KW - Glioblastoma
KW - Molecular expression classification
KW - Second-line therapy
UR - http://www.scopus.com/inward/record.url?scp=85062018458&partnerID=8YFLogxK
U2 - 10.1007/s12094-019-02066-2
DO - 10.1007/s12094-019-02066-2
M3 - Article
C2 - 30798512
AN - SCOPUS:85062018458
SN - 1699-048X
VL - 21
SP - 1364
EP - 1373
JO - Clinical and Translational Oncology
JF - Clinical and Translational Oncology
IS - 10
ER -
