Skip to main content

Advertisement

SpringerLink
Log in

Outcome after bevacizumab clinical trial therapy among recurrent grade III malignant glioma patients

  • Clinical Study - Patient Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Although outcome following bevacizumab among recurrent grade IV malignant glioma patients is documented as poor by several analyses, outcome for recurrent grade III patients following bevacizumab therapy has not been specifically evaluated. We performed a pooled analysis of 96 recurrent grade III malignant glioma patients enrolled on three consecutive phase II bevacizumab salvage trials to evaluate overall outcome following bevacizumab trial discontinuation. Outcome on the three bevacizumab trials, which included similar eligibility, treatment and assessment criteria, was comparable. Forty-nine patients who progressed on bevacizumab trial therapy and remained alive for at least 30 days elected to receive additional therapy. These patients achieved a median PFS-6 and OS of 30.6% (95% CI: 18.4, 43.6) and 10.3 months (95% CI: 5.2, 11.7), respectively. Among patients who continued bevacizumab therapy (n = 23) after study progression, PFS-6 and median OS were 39.1% (95% CI: 19.9, 58.0) and 9.2 months (95% CI: 5.2, 13.6), respectively, compared to 23.1% (95% CI: 9.4, 40.3; P = 0.51) and 10.3 months (95% CI: 2.5, 14.4; P = 0.91) for patients who initiated non-bevacizumab containing therapy (n = 26). Outcome after discontinuation of bevacizumab therapy for recurrent grade III malignant glioma patients is associated with improved outcome compared to historical data for recurrent grade IV malignant glioma patients. Salvage therapies following bevacizumab failure have modest activity for grade III malignant glioma patients that is independent of further bevacizumab continuation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. van den Bent MJ (2007) Anaplastic oligodendroglioma and oligoastrocytoma. Neurol Clin 25:1089–1109 ix–x

    Article  PubMed  Google Scholar 

  2. See SJ, Gilbert MR (2004) Anaplastic astrocytoma: diagnosis, prognosis, and management. Semin Oncol 31:618–634

    Article  PubMed  Google Scholar 

  3. Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law M, Flynn H, Passe S, Felten S, Brown PD, Shaw EG, Buckner JC (2006) A t(1; 19)(q10; p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 66:9852–9861

    Article  PubMed  CAS  Google Scholar 

  4. Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27:5874–5880. doi:10.1200/JCO.2009.23.6497

    Article  PubMed  CAS  Google Scholar 

  5. van den Bent MJ, Dubbink HJ, Sanson M, van der Lee-Haarloo CR, Hegi M, Jeuken JW, Ibdaih A, Brandes AA, Taphoorn MJ, Frenay M, Lacombe D, Gorlia T, Dinjens WN, Kros JM (2009) MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC brain tumor group study 26951. J Clin Oncol 27:5881–5886. doi:10.1200/JCO.2009.24.1034

    Article  PubMed  Google Scholar 

  6. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773

    Article  PubMed  CAS  Google Scholar 

  7. Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27:4150–4154. doi:10.1200/JCO.2009.21.9832

    Article  PubMed  CAS  Google Scholar 

  8. Lamborn KR, Yung WK, Chang SM, Wen PY, Cloughesy TF, Deangelis LM, Robins HI, Lieberman FS, Fine HA, Fink KL, Junck L, Abrey L, Gilbert MR, Mehta M, Kuhn JG, Aldape KD, Hibberts J, Peterson PM, Prados MD (2008) Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas. Neuro Oncol 10:162–170

    Article  PubMed  Google Scholar 

  9. Wu W, Lamborn KR, Buckner JC, Novotny PJ, Chang SM, O’Fallon JR, Jaeckle KA, Prados MD (2010) Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma. Neuro Oncol 12:164–172. doi:10.1093/neuonc/nop019

    Article  PubMed  CAS  Google Scholar 

  10. 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

    Article  PubMed  CAS  Google Scholar 

  11. 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

    Article  PubMed  CAS  Google Scholar 

  12. Chamberlain MC, Johnston S (2009) Salvage chemotherapy with bevacizumab for recurrent alkylator-refractory anaplastic astrocytoma. J Neurooncol 91:359–367

    Article  PubMed  CAS  Google Scholar 

  13. Chamberlain MC, Johnston S (2009) Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer 115:1734–1743

    Article  PubMed  CAS  Google Scholar 

  14. Desjardins A, Reardon DA, Herndon JE 2nd, Marcello J, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Bailey L, Bigner DD, Friedman AH, Friedman HS, Vredenburgh JJ (2008) Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas. Clin Cancer Res 14:7068–7073

    Article  PubMed  CAS  Google Scholar 

  15. Narayana A, Kelly P, Golfinos J, Parker E, Johnson G, Knopp E, Zagzag D, Fischer I, Raza S, Medabalmi P, Eagan P, Gruber ML (2009) Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival. J Neurosurg 110:173–180

    Article  PubMed  Google Scholar 

  16. Norden AD, Young GS, Setayesh K, Muzikansky A, Klufas R, Ross GL, Ciampa AS, Ebbeling LG, Levy B, Drappatz J, Kesari S, Wen PY (2008) Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 70:779–787

    Article  PubMed  CAS  Google Scholar 

  17. Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Sampson JH, Sathornsumetee S, McLendon RE, Herndon JE 2nd, Marcello JE, Norfleet J, Friedman AH, Bigner DD, Friedman HS (2009) Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study. Br J Cancer 101:1986–1994

    Article  PubMed  CAS  Google Scholar 

  18. Zuniga RM, Torcuator R, Jain R, Anderson J, Doyle T, Ellika S, Schultz L, Mikkelsen T (2009) Efficacy, safety and patterns of response and recurrence in patients with recurrent high-grade gliomas treated with bevacizumab plus irinotecan. J Neurooncol 91:329–336

    Article  PubMed  CAS  Google Scholar 

  19. Quant EC, Norden AD, Drappatz J, Muzikansky A, Doherty L, Lafrankie D, Ciampa A, Kesari S, Wen PY (2009) Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab. Neuro Oncol 11:550–555

    Article  PubMed  CAS  Google Scholar 

  20. Torcuator R, Zuniga R, Mohan YS, Rock J, Doyle T, Anderson J, Gutierrez J, Ryu S, Jain R, Rosenblum M, Mikkelsen T (2009) Initial experience with bevacizumab treatment for biopsy confirmed cerebral radiation necrosis. J Neurooncol 94:63–68

    Article  PubMed  CAS  Google Scholar 

  21. Sathornsumetee S, Desjardins A, Vredenburgh JJ, McLendon RE, Marcello J, Herndon JE, Mathe A, Hamilton M, Rich JN, Norfleet JA, Gururangan S, Friedman HS, Reardon DA (2010) Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma. Neuro Oncol 12:1300–1310. doi:10.1093/neuonc/noq099

    PubMed  CAS  Google Scholar 

  22. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Dowell JM, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Wagner M, Bigner DD, Friedman AH, Friedman HS (2007) Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 13:1253–1259

    Article  PubMed  CAS  Google Scholar 

  23. 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

    PubMed  CAS  Google Scholar 

  24. Fulton D, Urtasun R, Forsyth P (1996) Phase II study of prolonged oral therapy with etoposide (VP16) for patients with recurrent malignant glioma. J Neurooncol 27:149–155

    Article  PubMed  CAS  Google Scholar 

  25. Kesari S, Schiff D, Doherty L, Gigas DC, Batchelor TT, Muzikansky A, O’Neill A, Drappatz J, Chen-Plotkin AS, Ramakrishna N, Weiss SE, Levy B, Bradshaw J, Kracher J, Laforme A, Black PM, Folkman J, Kieran M, Wen PY (2007) Phase II study of metronomic chemotherapy for recurrent malignant gliomas in adults. Neuro Oncol 9:354–363

    Article  PubMed  CAS  Google Scholar 

  26. Prados MD, Lamborn KR, Chang S, Burton E, Butowski N, Malec M, Kapadia A, Rabbitt J, Page MS, Fedoroff A, Xie D, Kelley SK (2006) Phase 1 study of erlotinib HCl alone and combined with temozolomide in patients with stable or recurrent malignant glioma. Neuro Oncol 8:67–78

    Article  PubMed  CAS  Google Scholar 

  27. van den Bent MJ, Brandes AA, Rampling R, Kouwenhoven MC, Kros JM, Carpentier AF, Clement PM, Frenay M, Campone M, Baurain JF, Armand JP, Taphoorn MJ, Tosoni A, Kletzl H, Klughammer B, Lacombe D, Gorlia T (2009) Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol 27:1268–1274

    Article  PubMed  Google Scholar 

  28. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972

    Article  PubMed  Google Scholar 

  29. Iwamoto FM, Abrey LE, Beal K, Gutin PH, Rosenblum MK, Reuter VE, DeAngelis LM, Lassman AB (2009) Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma. Neurology 73:1200–1206

    Article  PubMed  CAS  Google Scholar 

  30. Norden AD, Drappatz J, Wen PY (2008) Novel anti-angiogenic therapies for malignant gliomas. Lancet neurol 7:1152–1160

    Article  PubMed  CAS  Google Scholar 

  31. Lu-Emerson C, Norden AD, Drappatz J, Quant EC, Beroukhim R, Ciampa AS, Doherty LM, Lafrankie DC, Ruland S, Wen PY (2010) Retrospective study of dasatinib for recurrent glioblastoma after bevacizumab failure. J Neurooncol. doi:10.1007/s11060-010-0489-x

  32. Reardon DA, Desjardins A, Peters K, Gururangan S, Sampson J, Rich JN, McLendon R, Herndon JE 2nd, Marcello J, Threatt S, Friedman AH, Vredenburgh JJ, Friedman HS (2011) Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. J Neurooncol 103:371–379. doi:10.1007/s11060-010-0403-6

    Article  PubMed  CAS  Google Scholar 

  33. Cohn AL, Bekaii-Saab TS, Bendell JC, Hurwitz H, Kozloff M, Roach N, Tezcan H, Feng S, Sing AP, Grothey A Clinical outcomes in bevacizumab (BV)-treated patients (pts) with metastatic colorectal cancer (mCRC): results from ARIES observational cohort study (OCS) and confirmation of BRiTE data beyond progression (BBP). Proc Am Soc Clin Oncol p284s

  34. Grothey A, Sugrue MM, Purdie DM, Dong W, Sargent D, Hedrick E, Kozloff M (2008) Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol 26:5326–5334

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH Grants P50-NS20023-29 and R37- CA11898-42; and a grant from Genentech Pharmaceuticals.

Author information

Authors and Affiliations

  1. Center for Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave; SW-460F, Boston, MA, 02215, USA

    David A. Reardon

  2. Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    Emil Lou, Ashley Sumrall, Scott Turner, Susan Boulton & Eric S. Lipp

  3. Department of Pediatrics, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    Henry S. Friedman

  4. Department of Cancer Center Biostatistics, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    James E. Herndon II

  5. Department of Medicine, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    Katherine Peters, Annick Desjardins & James J. Vredenburgh

  6. Department of Pathology, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    April Coan

  7. Department of Medicine (Neurology), Faculty of Medicine at Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Sith Sathornsumetee

  8. Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH, USA

    Jeremy N. Rich

Authors
  1. David A. Reardon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James E. Herndon II
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katherine Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Annick Desjardins
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. April Coan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emil Lou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ashley Sumrall
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Scott Turner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sith Sathornsumetee
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jeremy N. Rich
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Susan Boulton
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Eric S. Lipp
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Henry S. Friedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. James J. Vredenburgh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David A. Reardon.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reardon, D.A., Herndon, J.E., Peters, K. et al. Outcome after bevacizumab clinical trial therapy among recurrent grade III malignant glioma patients. J Neurooncol 107, 213–221 (2012). https://doi.org/10.1007/s11060-011-0740-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-011-0740-0

Keywords

Search

Navigation