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Prognostic factors in recurrent glioblastoma patients treated with bevacizumab

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The value of bevacizumab (BEV) in recurrent glioblastoma is unclear. Imaging parameters and progression-free survival (PFS) are problematic endpoints. Few data exist on clinical factors influencing overall survival (OS) in unselected patients with recurrent glioblastoma exposed to BEV. We retrospectively analyzed 174 patients with recurrent glioblastoma treated with BEV at two German brain tumor centers. We evaluated general patient characteristics, MGMT status, pretreatment, concomitant oncologic treatment and overall survival. Karnofsky performance score, number of prior chemotherapies, number of prior recurrences and combined treatment with irinotecan (IRI) were significantly associated with OS in univariate analysis. We did not find differences in OS related to sex, age, histology, MGMT status, prior surgical treatment or number of prior radiotherapies. Combined treatment with IRI and higher KPS both remained significantly associated with prolonged survival in multivariate analysis, but patients receiving IRI co-treatment had less advanced disease. Grouping into clinically relevant categories revealed an OS of 16.9 months from start of BEV in patients with first recurrence and KPS ≥ 80 % (n = 25). In contrast, in patients with second recurrence and KPS < 80 %, OS was 3.6 months (n = 27). Our observational data support an early use of BEV in patients with good performance status. The benefit of co-treatment with IRI in our cohort seems to be the result of biased patient recruitment.

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  1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. doi:10.1056/NEJMoa043330

    Article  CAS  PubMed  Google Scholar 

  2. Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, Cohen-Jonathan-Moyal E, Frappaz D, Henriksson R, Balana C, Chinot O, Ram Z, Reifenberger G, Soffietti R, Wick W (2014) EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 15:e395–e403. doi:10.1016/S1470-2045(14)70011-7

    Article  PubMed  Google Scholar 

  3. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS (2007) Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25:4722–4729. doi:10.1200/JCO.2007.12.2440

    Article  CAS  PubMed  Google Scholar 

  4. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733–4740. doi:10.1200/JCO.2008.19.8721

    Article  CAS  PubMed  Google Scholar 

  5. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:740–745. doi:10.1200/JCO.2008.16.3055

    Article  CAS  PubMed  Google Scholar 

  6. Gutin PH, Iwamoto FM, Beal K, Mohile NA, Karimi S, Hou BL, Lymberis S, Yamada Y, Chang J, Abrey LE (2009) Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 75:156–163. doi:10.1016/j.ijrobp.2008.10.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lai A, Tran A, Nghiemphu PL, Pope WB, Solis OE, Selch M, Filka E, Yong WH, Mischel PS, Liau LM, Phuphanich S, Black K, Peak S, Green RM, Spier CE, Kolevska T, Polikoff J, Fehrenbacher L, Elashoff R, Cloughesy T (2011) Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 29:142–148. doi:10.1200/JCO.2010.30.2729

    Article  CAS  PubMed  Google Scholar 

  8. Narayana A, Gruber D, Kunnakkat S, Golfinos JG, Parker E, Raza S, Zagzag D, Eagan P, Gruber ML (2012) A clinical trial of bevacizumab, temozolomide, and radiation for newly diagnosed glioblastoma. J Neurosurg 116:341–345. doi:10.3171/2011.9.JNS11656

    Article  CAS  PubMed  Google Scholar 

  9. Batchelor TT, Reardon DA, de Groot JF, Wick W, Weller M (2014) Antiangiogenic therapy for glioblastoma: current status and future prospects. Clin Cancer Res 20:5612–5619. doi:10.1158/1078-0432.CCR-14-0834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Norden AD, Drappatz J, Wen PY (2009) Antiangiogenic therapies for high-grade glioma. Nat Rev Neurol 5:610–620. doi:10.1038/nrneurol.2009.159

    Article  CAS  PubMed  Google Scholar 

  11. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370:709–722. doi:10.1056/NEJMoa1308345

    Article  CAS  PubMed  Google Scholar 

  12. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370:699–708. doi:10.1056/NEJMoa1308573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Raizer JJ, Grimm S, Chamberlain MC, Nicholas MK, Chandler JP, Muro K, Dubner S, Rademaker AW, Renfrow J, Bredel M (2010) A phase 2 trial of single-agent bevacizumab given in an every-3-week schedule for patients with recurrent high-grade gliomas. Cancer 116:5297–5305. doi:10.1002/cncr.25462

    Article  CAS  PubMed  Google Scholar 

  14. Khasraw M, Ameratunga MS, Grant R, Wheeler H, Pavlakis N (2014) Antiangiogenic therapy for high-grade glioma. Cochrane Database Syst Rev 9:CD008218. doi:10.1002/14651858.CD008218.pub3

    PubMed  Google Scholar 

  15. Weller M, Cloughesy T, Perry JR, Wick W (2013) Standards of care for treatment of recurrent glioblastoma—are we there yet? Neuro Oncol 15:4–27. doi:10.1093/neuonc/nos273

    Article  PubMed  Google Scholar 

  16. Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B, van den Bent MJ (2014) Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol 15:943–953. doi:10.1016/S1470-2045(14)70314-6

    Article  CAS  PubMed  Google Scholar 

  17. Wick W, Brandes A, Gorlia T, Bendszus M, Sahm F, Taal W, Taphoorn M, Domont J, Idbaih A, Campone M, Clement PM, Stupp R, Fabbro M, Dubois F, Bais C, Musmeci D, Platten M, Weller M, Golfinopoulos V, van den Bent M (2015) Phase III trial exploring the combination of bevacizumab and lomustine in patients with first recurrence of a glioblastoma: the EORTC 26101 trial. Neuro Oncol 17:v1. doi:10.1093/neuonc/nov306

    Article  Google Scholar 

  18. Sandmann T, Bourgon R, Garcia J, Li C, Cloughesy T, Chinot OL, Wick W, Nishikawa R, Mason W, Henriksson R, Saran F, Lai A, Moore N, Kharbanda S, Peale F, Hegde P, Abrey LE, Phillips HS, Bais C (2015) Patients with proneural glioblastoma may derive overall survival benefit from the addition of bevacizumab to first-line radiotherapy and temozolomide: retrospective analysis of the AVAglio trial. J Clin Oncol 33:2735–2744. doi:10.1200/JCO.2015.61.5005

    Article  CAS  PubMed  Google Scholar 

  19. Hamza MA, Mandel JJ, Conrad CA, Gilbert MR, Yung WK, Puduvalli VK, DeGroot JF (2014) Survival outcome of early versus delayed bevacizumab treatment in patients with recurrent glioblastoma. J Neurooncol 119:135–140. doi:10.1007/s11060-014-1460-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Piccioni DE, Selfridge J, Mody RR, Chowdhury R, Li S, Lalezari S, Wawrzynski J, Quan J, Zurayk M, Chou AP, Sanchez DE, Liau LM, Ellingson BM, Pope WB, Nghiemphu PL, Green RM, Wang HJ, Yong WH, Elashoff R, Cloughesy TF, Lai A (2014) Deferred use of bevacizumab for recurrent glioblastoma is not associated with diminished efficacy. Neuro-oncology 16:815–822. doi:10.1093/neuonc/nou028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Friedman HS, Petros WP, Friedman AH, Schaaf LJ, Kerby T, Lawyer J, Parry M, Houghton PJ, Lovell S, Rasheed K, Cloughsey T, Stewart ES, Colvin OM, Provenzale JM, McLendon RE, Bigner DD, Cokgor I, Haglund M, Rich J, Ashley D, Malczyn J, Elfring GL, Miller LL (1999) Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol 17:1516–1525

    CAS  PubMed  Google Scholar 

  22. Chamberlain MC (2002) Salvage chemotherapy with CPT-11 for recurrent glioblastoma multiforme. J Neurooncol 56:183–188

    Article  PubMed  Google Scholar 

  23. Raymond E, Fabbro M, Boige V, Rixe O, Frenay M, Vassal G, Faivre S, Sicard E, Germa C, Rodier JM, Vernillet L, Armand JP (2003) Multicentre phase II study and pharmacokinetic analysis of irinotecan in chemotherapy-naive patients with glioblastoma. Ann Oncol 14:603–614

    Article  CAS  PubMed  Google Scholar 

  24. Tabouret E, Barrie M, Thiebaut A, Matta M, Boucard C, Autran D, Loundou A, Chinot O (2013) Limited impact of prognostic factors in patients with recurrent glioblastoma multiforme treated with a bevacizumab-based regimen. J Neurooncol 114:191–198

    Article  CAS  PubMed  Google Scholar 

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The Dr. Senckenberg Institute of Neurooncology is supported by the Dr. Senckenberg Foundation and the Hertie Foundation. J.P.S. is “Hertie Professor of Neurooncology”.

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Correspondence to Martin Glas or Oliver Bähr.

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Conflict of Interest

Joachim P. Steinbach has served as a consultant for Roche the European distributer of Bevacizumab. Ulrich Herrlinger has served as a consultant for Roche. He has also received scientific grants and speakers honoraria from Roche. Johannes Rieger has served as a consultant for Roche. Martin Glas has served as a consultant for Roche and has received speakers honoraria form Roche. Oliver Bähr has served as a consultant for Roche and has received travel grants from Roche. Niklas Schäfer received honoraria from Roche. All other authors declare that they have no conflict of interest.

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Christina Schaub and Julia Tichy have contributed equally to this work.

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Schaub, C., Tichy, J., Schäfer, N. et al. Prognostic factors in recurrent glioblastoma patients treated with bevacizumab. J Neurooncol 129, 93–100 (2016).

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