It is an educational PPT presentation which summaries the most recent updates in the standard of care for newly diagnosed GBM patients.

1. Glioblastoma Multiforme
(GBM)
Recent updates; evidence-based medicine
“PART-I”
By
Osama Elzaafarany, MBBcH, M.S.
Medical Oncology Registrar
KAUH – Jeddah, KSA.
March 2019

2. Introduction:
Here, we will present the standard of care in treatment
for newly diagnosed GBM.
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● Aim: To be oriented by the “practice-changing trials” .
● Contents:
➢ Epidemiology (1 slide)
➢ Molecular biology & genetics (4 slides)
➢ What is the current standard of care (1 slide)
➢ EORTC/NCIC trial (3 slides)
➢ RT trials (2 slides)
➢ Avastin (2 slides)
➢ Gliadel wafers (1 slide)
➢ TTF (2 slides)
➢ Immunotherapy principles & updates (2 slides)

3. Epidemiology:

5. Genetics:
(I) Mutations in the isocitrate dehydrogenase (IDH)
gene:
➢ 80% of secondary GBM but in only 5% of primary GBM.
➢ The presence of IDH mutation may identify a better prognostic
subgroup within GBM patients.
(II) EGFR:
➢ Approximately 40–50% of GBM have EGFR gene amplification.
➢ higher levels of gene amplification appear to correlate with poorer
survival outcomes.

7. + TTF

15. Bevacizumab (Avastin) Role:
can be used to ameliorate
1) Radiation-induced worsening of edema.
2) Mass effect in newly diagnosed GBM patients.

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Stupp R, Taillibert S, Kanner A, et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance
Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017;318(23):2306-
2316.
700 pts.
● Newly diagnosed GBM
● Post surgery
● Post CCRT
Adjuvant TMZ – 6 ms
TMZ – 6 ms + TTF Increase OS

19. Immunotherapy:
Investigional
● Immune-checkpoint inhibitors:
➢ Programmed cell death protein (PD-1) prevents the immune system
from targeting cancer cells.
➢ e.g. Pembrolizumab: humanized monoclonal immunoglobulin (Ig) G4
antibody directed against human cell surface receptor PD-1.
● Vaccination:
➢ Negative results from several phase II and phase III trials.
➢ e.g. Celldex's Rintega (rindopepimut).
● Oncolytic viruses:
➢ Recombinant, laboratory-engineered viruses met with an improved
molecular-based understanding of virology and cancer genetics.

20. Ongoing Phase 1 Study:
 EGFRvIII-Directed CAR T Cells + PD-1 Inhibition.
 Newly Diagnosed Glioblastoma.
 Post-surgical resection.
 MGMT-Unmethylated.
 EGFR-vIII +ve.
ClinicalTrials.gov Identifier: NCT03726515

22. Take Home Message:
Lines of treatment of newly diagnosed GBM: (evidence-based)
➢ Surgery: max. safe resection
➢ Radiotherapy: 60 Gy (2Gy/Fx), partial brain.
➢ Chemotherapy: TMZ + RT then 6 ms TMZ.
➢ Biological agents: Avastin in certain indications.
➢ TTF (new standard of care + maintenance TMZ).
➢ Vaccines: no role.
➢ Targeted therapy: no role (e.g TKIs).
➢ PD-1 inhibitors: awaiting for results (promising).
➢ Supportive care: cortz + anti-epileptics.