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Impact of tapering and discontinuation of bevacizumab in patients with progressive glioblastoma

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Abstract

Bevacizumab is frequently used in patients with progressive glioblastoma raising questions regarding frequency of treatments, dosage, duration of therapy and the possibility of tapering and discontinuation for selected patient groups. We retrospectively assessed the safety and outcome of tapering and discontinuation of bevacizumab therapy for reasons other than disease progression and toxicity in 19 patients with progressive glioblastoma receiving bevacizumab for at least 6 months. In 10 of the 19 patients tapering bevacizumab resulted in complete discontinuation and reinitiation after disease progression during halted treatment. As a comparison group 33 patients with bevacizumab for at least 6 months continuously dosed at 10 mg/kg every 2 weeks were selected. Age and Karnofsky performance status at start of bevacizumab were similar in both groups. Influenced by the selection process, progression-free survival (PFS) and overall survival (OS) were longer in the group receiving a tapered and discontinued bevacizumab regimen (PFS 22.7 versus 11.2 months, HR 0.33, p-value = 0.01; OS 29.9 versus 15.5 months, HR 0.22, p-value = 0.001) with a median time of discontinuation of 4.5 months (range: 1.9–44.2 months). Stable disease or partial response according to RANO at ≥3 months was achieved in 89 % of patients with reinitiated bevacizumab therapy after discontinuation. These data indicate that tapering and discontinuation of bevacizumab therapy for other reasons than progression is feasible without an increased risk for tumor rebound or unresponsiveness to reinitiated bevacizumab therapy.

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References

  1. Weller M, Cloughesy T, Perry JR, Wick W (2013) Standards of care for treatment of recurrent glioblastoma—are we there yet? Neuro Oncol 15(1):4–27

    Article  PubMed  Google Scholar 

  2. Jo J, Schiff D, Purow B (2012) Angiogenic inhibition in high-grade gliomas: past, present and future. Expert Rev Neurother 12(6):733–747

    Article  CAS  PubMed  Google Scholar 

  3. 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(5):740–745

    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(28):4733–4740

    Article  CAS  PubMed  Google Scholar 

  5. Gil-Gil MJ, Mesia C, Rey M, Bruna J (2013) Bevacizumab for the treatment of glioblastoma. Clin Med Insights Oncol 7:123–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Stupp R, Weller M (2014) Questions regarding the optimal use of bevacizumab in glioblastoma: a moving target. Neuro Oncol 16(6):765–767

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chamberlain MC (2011) Bevacizumab for the treatment of recurrent glioblastoma. Clin Med Insights Oncol 5:117–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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(9):943–953

    Article  CAS  PubMed  Google Scholar 

  9. Wick W, Brandes AA, 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-Oncology 17:v1–v1. doi:10.1093/neuonc/nov306

    Article  Google Scholar 

  10. 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(8):709–722

    Article  CAS  PubMed  Google Scholar 

  11. 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(8):699–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Soffietti R, Trevisan E, Ruda R (2014) What have we learned from trials on antiangiogenic agents in glioblastoma? Expert Rev Neurother 14(1):1–3

    Article  CAS  PubMed  Google Scholar 

  13. 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(25):2735–2744

    Article  CAS  PubMed  Google Scholar 

  14. Wagle N, Nghiemphu L, Lai A, Pope W, Mischel PS, Cloughesy T (2010) Update and developments in the treatment of glioblastoma multiforme—focus on bevacizumab. Pharmgenomics Pers Med 3:79–85

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Anderson MD, Hamza MA, Hess KR, Puduvalli VK (2014) Implications of bevacizumab discontinuation in adults with recurrent glioblastoma. Neuro Oncol 16(6):823–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Blumenthal DT, Mendel L, Bokstein F (2016) The optimal regimen of bevacizumab for recurrent glioblastoma: does dose matter? J Neurooncol 127(3):503

    Article  CAS  PubMed  Google Scholar 

  17. Kaloshi G, Brace G, Rroji A, Bushati T, Roci E, Hoxha M, Fejzo G, Petrela M (2013) Bevacizumab alone at 5 mg/kg in an every-3-week schedule for patients with recurrent glioblastomas: a single center experience. Tumori 99(5):601–603

    CAS  PubMed  Google Scholar 

  18. Levin VA, Mendelssohn ND, Chan J, Stovall MC, Peak SJ, Yee JL, Hui RL, Chen DM (2015) Impact of bevacizumab administered dose on overall survival of patients with progressive glioblastoma. J Neurooncol 122(1):145–150

    Article  CAS  PubMed  Google Scholar 

  19. 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(22):5297–5305

    Article  CAS  PubMed  Google Scholar 

  20. Simon R, Makuch RW (1984) A non-parametric graphical representation of the relationship between survival and the occurrence of an event: application to respnder versus non-responder bias. Stat Med 3:35–44

    Article  CAS  PubMed  Google Scholar 

  21. Scartozzi M, Giampieri R, Del Prete M, Faloppi L, Bianconi M, Vincenzi B, Tonini G, Santini D, Cascinu S (2014) Selected gastrointestinal cancer presentations from the American Society of Clinical Oncology annual meeting 2013 in review: it is not about the destination, it is about the journey. Expert Opin Pharmacother 15(1):143–150

    Article  PubMed  Google Scholar 

  22. Moscetti L, Nelli F, Fabbri MA, Sperduti I, Alesini D, Cortesi E, Gemma D, Gamucci T, Grande R, Pavese I, Franco D, Ruggeri EM (2013) Maintenance single-agent bevacizumab or observation after first-line chemotherapy in patients with metastatic colorectal cancer: a multicenter retrospective study. Invest New Drugs 31(4):1035–1043

    Article  CAS  PubMed  Google Scholar 

  23. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9(3):157–173

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Neurology Clinic & National Center for Tumor Disease, University of Heidelberg and German Cancer Research Center, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Anne Hertenstein, Oliver Menn, Benedikt Wiestler, Frank Winkler, Michael Platten, Wolfgang Wick & Antje Wick

  2. Clinical Cooperation Units Neurooncology, German Cancer Research Center, 69120, Heidelberg, Germany

    Anne Hertenstein, Benedikt Wiestler, Frank Winkler & Wolfgang Wick

  3. Clinical Cooperation Unit Brain Tumor Immunology, German Cancer Research Center, 69120, Heidelberg, Germany

    Michael Platten

  4. Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Thomas Hielscher

Authors
  1. Anne Hertenstein
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  2. Thomas Hielscher
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  3. Oliver Menn
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  4. Benedikt Wiestler
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  6. Michael Platten
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  7. Wolfgang Wick
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  8. Antje Wick
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Correspondence to Antje Wick.

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The authors declare no conflicts of interest.

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For this type of study formal consent is not required. The study has been conducted within the umbrella ethics approval of the NCT Heidelberg.

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Hertenstein, A., Hielscher, T., Menn, O. et al. Impact of tapering and discontinuation of bevacizumab in patients with progressive glioblastoma. J Neurooncol 129, 533–539 (2016). https://doi.org/10.1007/s11060-016-2206-x

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  • DOI: https://doi.org/10.1007/s11060-016-2206-x

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