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Review
. 2021 Mar 22;9(3):324.
doi: 10.3390/biomedicines9030324.

Current FDA-Approved Therapies for High-Grade Malignant Gliomas

Jacob P Fisher  1 , David C Adamson  2   3
Affiliations
Review

Current FDA-Approved Therapies for High-Grade Malignant Gliomas

Jacob P Fisher et al. Biomedicines. .

Abstract

The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.

Keywords: FDA-approved; bevacizumab; carmustine; glioblastoma; high-grade glioma; lomustine; malignant glioma; standard of care; temozolomide; tumor treatment fields.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Survival by extent of resection for high-grade gliomas. (B) Recurrence by extent of resection for high-grade gliomas. Greater than 70% extent of resection compared to less than 70% extent of resection [8].
Figure 2
Figure 2
Kaplan–Meier estimates of overall survival of glioblastoma patients with radiotherapy alone compared to radiotherapy and temozolomide [5]. Used with permission.
Figure 3
Figure 3
Kaplan–Meier estimates of progression-free survival of glioblastoma patients with radiotherapy alone compared to radiotherapy and temozolomide [5]. Used with permission.
Figure 4
Figure 4
Kaplan–Meier estimates of overall survival of glioblastoma patients with a methylated MGMT promoter compared to an unmethylated MGMT promoter [16]. Used with permission.
Figure 5
Figure 5
(A) Progression-free survival of glioblastoma patients with tumor-treating fields plus temozolomide compared to temozolomide alone. (B) Overall survival of glioblastoma patients with tumor-treating fields plus temozolomide compared to temozolomide alone [36]. Used with permission.
Figure 6
Figure 6
Therapies in clinical trials for high-grade gliomas [77]. Used with permission.
See this image and copyright information in PMC

References

    1. Ostrom Q.T., Gittleman H., Liao P., Rouse C., Chen Y., Dowling J., Wolinsky Y., Kruchko C., Barnholtz-Sloan J. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncol. 2014;16:iv1–iv63. doi: 10.1093/neuonc/nou223. - DOI - PMC - PubMed
    1. Survival Rates for Selected Adult Brain and Spinal Cord Tumors. [(accessed on 30 September 2020)]; Available online: https://www.cancer.org/cancer/brain-spinal-cord-tumors-adults/detection-....
    1. Louis D.N., Perry A., Reifenberger G., von Deimling A., Figarella-Branger D., Cavenee W.K., Ohgaki H., Wiestler O.D., Kleihues P., Ellison D.W. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary. Acta Neuropathol. 2016;131:803–820. doi: 10.1007/s00401-016-1545-1. - DOI - PubMed
    1. Fernandes C., Costa A., Osório L., Lago R.C., Linhares P., Carvalho B., Caeiro C. Current standards of care in glioblastoma therapy. In: De Vleeschouwer S., editor. Glioblastoma. Codon Publications; Brisbane, Australia: 2017. Chapter 11. - PubMed
    1. Stupp R., Mason W.P., van den Bent M.J., Weller M., Fisher B., Taphoorn M.J., Belanger K., Brandes A.A., Marosi C., Bogdahn U., et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005;352:987–996. doi: 10.1056/NEJMoa043330. - DOI - PubMed

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