Current status and research progress of medical therapy for high-grade gliomas_West China Medical Journal

Authors：

ZENG Yuanyuan ,  LIU Lei

Department of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LIU Lei, Email: liuleihx@gmail.com

Keywords：

High-grade gliomas; Chemotherapy; Immunotherapy; Targeted therapy

DOI：

10.7507/1002-0179.201908057

Video：

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Abstract Full text Figures/Tables Video References Cited by

High-grade gliomas are the most common malignant primary central nervous system tumors with poor prognosis. The operation based on the principle of maximum safe resection of tumors, combined with radiation therapy and chemotherapy, is the primary treatment method. This treatment only delays the progression of high-grade gliomas, and almost all patients eventually develop disease progression or relapse. With the development of molecular biology, immunology, and genomics, people have a deeper understanding of the pathogenesis of gliomas. Targeted therapy, immunotherapy, and other comprehensive treatments are expected to become potential treatments for high-grade gliomas. This article reviews the current status of medical treatment of primary and recurrent high-grade gliomas, and the research progress of high-grade gliomas in targeted therapy and immunotherapy.

Citation： ZENG Yuanyuan, LIU Lei. Current status and research progress of medical therapy for high-grade gliomas. West China Medical Journal, 2019, 34(10): 1184-1191. doi: 10.7507/1002-0179.201908057 Copy

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24.	Weller M, Tabatabai G, Kästner B, et al. MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR trial. Clin Cancer Res, 2015, 21(9): 2057-2064.
25.	Brandes AA, Finocchiaro G, Zagonel V, et al. AVAREG: a phase II, randomized, noncomparative study of fotemustine or bevacizumab for patients with recurrent glioblastoma. Neuro Oncol, 2016, 18(9): 1304-1312.
26.	Brandes AA, Tosoni A, Amistà P, et al. How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial. Neurology, 2004, 63(7): 1281-1284.
27.	Schmidt F, Fischer J, Herrlinger U, et al. PCV chemotherapy for recurrent glioblastoma. Neurology, 2006, 66(4): 587-589.
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31.	Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med, 2014, 370(8): 709-722.
32.	Taillibert S, Vincent LA, Granger B, et al. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology, 2009, 72(18): 1601-1606.
33.	Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res, 2007, 13(4): 1253-1259.
34.	Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol, 2009, 27(28): 4733-4740.
35.	Taal W, Oosterkamp HM, Walenkamp AM, et al. 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, 2014, 15(9): 943-953.
36.	Wick W, Gorlia T, Bendszus M, et al. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med, 2017, 377(20): 1954-1963.
37.	Badruddoja MA, Pazzi M, Sanan A, et al. Phase II study of bi-weekly temozolomide plus bevacizumab for adult patients with recurrent glioblastoma. Cancer Chemother Pharmacol, 2017, 80(4): 715-721.
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46.	Rich JN, Reardon DA, Peery T, et al. Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol, 2004, 22(1): 133-142.
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48.	Reardon DA, Nabors LB, Mason WP, et al. Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma. Neuro Oncol, 2015, 17(3): 430-439.
49.	Neyns B, Sadones J, Joosens E, et al. Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol, 2009, 20(9): 1596-1603.
50.	Westphal M, Heese O, Steinbach JP, et al. A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur J Cancer, 2015, 51(4): 522-532.
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52.	Reardon DA, Lassman AB, van den Bent M, et al. Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma. Neuro Oncol, 2017, 19(7): 965-975.
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1. Pranckeviciene A, Bunevicius A. Depression screening in patients with brain tumors: a review. CNS Oncol, 2015, 4(2): 71-78.
2. 国家卫生健康委员会医政医管局. 脑胶质瘤诊疗规范(2018年版). 中华神经外科杂志, 2019, 35(3): 217-239.
3. Ostrom QT, Bauchet L, Davis FG, et al. The epidemiology of glioma in adults: a " state of the science” review. Neuro Oncol, 2014, 16(7): 896-913.
4. Gilbert MR, Wang M, Aldape KD, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol, 2013, 31(32): 4085-4091.
5. Khan L, Soliman H, Sahgal A, et al. External beam radiation dose escalation for high grade glioma. Cochrane Database Syst Rev, 2016(8): CD011475.
6. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med, 2005, 352(10): 987-996.
7. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol, 2009, 10(5): 459-466.
8. De Carli E, Wang X, Puget S. IDH1 and IDH2 mutations in gliomas. N Engl J Med, 2009, 360(21): 2248.
9. 中国脑胶质瘤协作组, 中国脑胶质瘤基因组图谱计划. 中国脑胶质瘤分子诊疗指南. 中华神经外科杂志, 2014, 30(5): 435-444.
10. Jiang T, Mao Y, Ma W, et al. CGCG clinical practice guidelines for the management of adult diffuse gliomas. Cancer Lett, 2016, 375(2): 263-273.
11. Louis DN, Perry A, Reifenberger G, et al. The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol, 2016, 131(6): 803-820.
12. Gorlia T, van den Bent MJ, Hegi ME, et al. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol, 2008, 9(1): 29-38.
13. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med, 2005, 352(10): 997-1003.
14. Herrlinger U, Tzaridis T, Mack F, et al. Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. Lancet, 2019, 393(10172): 678-688.
15. van den Bent MJ, Brandes AA, Taphoorn MJ, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol, 2013, 31(3): 344-350.
16. van den Bent MJ, Baumert B, Erridge SC, et al. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet, 2017, 390(10103): 1645-1653.
17. Kouwenhoven MC, Gorlia T, Kros JM, et al. Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: a report from EORTC study 26951. Neuro Oncol, 2009, 11(6): 737-746.
18. Cairncross G, Wang M, Shaw E, et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol, 2013, 31(3): 337-343.
19. Franceschi E, Bartolotti M, Tosoni A, et al. The effect of re-operation on survival in patients with recurrent glioblastoma. Anticancer Res, 2015, 35(3): 1743-1748.
20. Minniti G, Agolli L, Falco T, et al. Hypofractionated stereotactic radiotherapy in combination with bevacizumab or fotemustine for patients with progressive malignant gliomas. J Neurooncol, 2015, 122(3): 559-566.
21. Omuro A, Chan TA, Abrey LE, et al. Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma. Neuro Oncol, 2013, 15(2): 242-250.
22. Perry JR, Bélanger K, Mason WP, et al. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol, 2010, 28(12): 2051-2057.
23. Wick A, Felsberg J, Steinbach JP, et al. Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma. J Clin Oncol, 2007, 25(22): 3357-3361.
24. Weller M, Tabatabai G, Kästner B, et al. MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR trial. Clin Cancer Res, 2015, 21(9): 2057-2064.
25. Brandes AA, Finocchiaro G, Zagonel V, et al. AVAREG: a phase II, randomized, noncomparative study of fotemustine or bevacizumab for patients with recurrent glioblastoma. Neuro Oncol, 2016, 18(9): 1304-1312.
26. Brandes AA, Tosoni A, Amistà P, et al. How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial. Neurology, 2004, 63(7): 1281-1284.
27. Schmidt F, Fischer J, Herrlinger U, et al. PCV chemotherapy for recurrent glioblastoma. Neurology, 2006, 66(4): 587-589.
28. Fabrini MG, Silvano G, Lolli I, et al. A multi-institutional phase II study on second-line fotemustine chemotherapy in recurrent glioblastoma. J Neurooncol, 2009, 92(1): 79-86.
29. Wick W, Puduvalli VK, Chamberlain MC, et al. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol, 2010, 28(7): 1168-1174.
30. Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med, 2014, 370(8): 699-708.
31. Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med, 2014, 370(8): 709-722.
32. Taillibert S, Vincent LA, Granger B, et al. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology, 2009, 72(18): 1601-1606.
33. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res, 2007, 13(4): 1253-1259.
34. Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol, 2009, 27(28): 4733-4740.
35. Taal W, Oosterkamp HM, Walenkamp AM, et al. 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, 2014, 15(9): 943-953.
36. Wick W, Gorlia T, Bendszus M, et al. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med, 2017, 377(20): 1954-1963.
37. Badruddoja MA, Pazzi M, Sanan A, et al. Phase II study of bi-weekly temozolomide plus bevacizumab for adult patients with recurrent glioblastoma. Cancer Chemother Pharmacol, 2017, 80(4): 715-721.
38. Mrugala MM, Crew LK, Fink JR, et al. Carboplatin and bevacizumab for recurrent malignant glioma. Oncol Lett, 2012, 4(5): 1082-1086.
39. Thompson EM, Dosa E, Kraemer DF, et al. Treatment with bevacizumab plus carboplatin for recurrent malignant glioma. Neurosurgery, 2010, 67(1): 87-93.
40. Iwamoto FM, Lamborn KR, Robins HI, et al. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (north American brain tumor consortium study 06-02). Neuro Oncol, 2010, 12(8): 855-861.
41. Pan E, Yu D, Yue B, et al. A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. J Neurooncol, 2012, 110(1): 111-118.
42. Reardon DA, Groves MD, Wen PY, et al. A phase I/II trial of pazopanib in combination with lapatinib in adult patients with relapsed malignant glioma. Clin Cancer Res, 2013, 19(4): 900-908.
43. Kreisl TN, McNeill KA, Sul J, et al. A phase I/II trial of vandetanib for patients with recurrent malignant glioma. Neuro Oncol, 2012, 14(12): 1519-1526.
44. Rao SK, Edwards J, Joshi AD, et al. A survey of glioblastoma genomic amplifications and deletions. J Neurooncol, 2010, 96(2): 169-179.
45. Mellinghoff IK, Wang MY, Vivanco I, et al. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med, 2005, 353(19): 2012-2024.
46. Rich JN, Reardon DA, Peery T, et al. Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol, 2004, 22(1): 133-142.
47. van den Bent MJ, Brandes AA, Rampling R, et al. Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol, 2009, 27(8): 1268-1274.
48. Reardon DA, Nabors LB, Mason WP, et al. Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma. Neuro Oncol, 2015, 17(3): 430-439.
49. Neyns B, Sadones J, Joosens E, et al. Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol, 2009, 20(9): 1596-1603.
50. Westphal M, Heese O, Steinbach JP, et al. A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur J Cancer, 2015, 51(4): 522-532.
51. Reardon DA, Wen PY, Mellinghoff IK. Targeted molecular therapies against epidermal growth factor receptor: past experiences and challenges. Neuro Oncol, 2014, 16(Suppl 8): viii7-viii13.
52. Reardon DA, Lassman AB, van den Bent M, et al. Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma. Neuro Oncol, 2017, 19(7): 965-975.
53. AbbVie. A study of ABT-414 in subjects with newly diagnosed glioblastoma (GBM) with epidermal growth factor receptor (EGFR) amplification (intellance1). (2019-07-12)[2019-08-11]. https://clinicaltrials.gov/ct2/show/NCT02573324?cond=NCT02573324&rank=1.
54. Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature, 2015, 523(7560): 337-341.
55. Davies DC. Blood-brain barrier breakdown in septic encephalopathy and brain tumours. J Anat, 2002, 200(6): 639-646.
56. Omuro A, Vlahovic G, Lim M, et al. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro Oncol, 2018, 20(5): 674-686.
57. Heiland DH, Haaker G, Delev D, et al. Comprehensive analysis of PD-L1 expression in glioblastoma multiforme. Oncotarget, 2017, 8(26): 42214-42225.
58. Nduom EK, Wei J, Yaghi NK, et al. PD-L1 expression and prognostic impact in glioblastoma. Neuro Oncol, 2016, 18(2): 195-205.
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