New Directions in the Treatment of Glioblastoma

Zachary J. Reitman, MD, PhD; Frank Winkler, MD, PhD; Andrew E. H. Elia, MD, PhD


Semin Neurol. 2018;38(1):50-61. 

In This Article

Salvage Therapies for Recurrent Gbm

Treatment options for recurrent GBM include reresection, reirradiation, and systemic therapies.[33] Despite numerous clinical trials, no standard regimen has been established for recurrent GBM, due to a paucity of randomized evidence and disease heterogeneity in single-arm prospective studies. Reresection and reirradiation are controversial but may be appropriate for select patients with good performance status, small tumor volume, and no involvement of critical brain structures,[34,35] with radiation often involving hypofractionated stereotactic approaches.[33,34] Nitrosoureas, temozolomide, and bevacizumab represent the most widely accepted systemic therapies.[33] Temozolomide rechallenge appears most beneficial for patients with MGMT (O6-methylguanine methyltransferase) promoter methylation.[36] Bevacizumab efficacy was first demonstrated in two phase II trials,[37,38] which led to its approval as monotherapy in 2009 and subsequent widespread adoption in clinical practice. It has since been tested in combination with numerous agents including nitrosoureas. Notably, addition of lomustine to bevacizumab improved overall survival in the BELOB phase II randomized trial[39] but failed to confer a survival benefit in a subsequent phase III trial.[40] No targeted agents have demonstrated efficacy superior to that of alkylating chemotherapy, with notable examples including the kinase inhibitor enzastaurin[41] and the VEGFR inhibitor cediranib,[42] both studied in randomized phase III trials. Given multiple treatment options, therapy selection in recurrent GBM should be individualized, taking into account patient fitness, neurological symptoms, volume of disease, involvement of critical brain structures, and overlap with prior radiation fields. Regardless of therapy choice, overall survival is dismal at ~6 to 12 months after recurrence.