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

• A. F. Cardona ^[4] ; L. Rojas ^[1] ; B. Wills ^[5] ; A. Ruiz-Patiño ^[5] ; L. Abril ^[5] ; F. Hakim ^[2] ; E. Jiménez ^[2] ; N. Useche ^[2] ; S. Bermúdez ^[2] ; J. A. Mejía ^[2] ; J. F. Ramón ^[2] ; H. Carranza ^[4] ; C. Vargas ^[4] ; J. Otero ^[5] ; P. Archila ^[5] ; J. Rodríguez ^[5] ; J. Rodríguez ^[5] ; J. Behaine ^[2] ; D. González ^[2] ; J. Jacobo ^[2] ; H. Cifuentes ^[6] ; O. Feo ^[6] ; P. Penagos ^[6] ; D. Pineda ^[7] ; L. Ricaurte ^[5] ; L. E. Pino ^[8] ; C. Vargas ^[7] ; J. C. Marquez ^[7] ; M. I. Mantilla ^[7] ; L. D. Ortiz ^[9] ; C. Balaña ^[3] ; R. Rosell ^[3] ; Z. L. Zatarain-Barrón ^[10] ; O. Arrieta ^[10]
  1. [1] Hospital Universitario San Ignacio

     Hospital Universitario San Ignacio

     Colombia

     
  2. [2] Universidad El Bosque

     Universidad El Bosque

     Colombia

     
  3. [3] Institute Catalá Oncología

     Institute Catalá Oncología

     Barcelona, España

     
  4. [4] Clinical and Translational Oncology Group, Institute of Oncology, Clínica del Country, Bogotá
  5. [5] Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá
  6. [6] Neurosurgery Department, Clínica del Country, Bogotá
  7. [7] Radiology Department, Clínica del Country, Bogotá
  8. [8] Clinical Oncology Department, Fundación Santa fe de Bogotá
  9. [9] Clinical Oncology Department, Clínica de Las Américas, Medellín
  10. [10] nstituto Nacional de Cancerología, México City

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 21, Nº. 10, 2019, págs. 1364-1373
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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.