Clinical Course of Recurrent Glioblastoma in the Era of Molecular Diagnosis

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Glioblastoma multiforme is the most common and most malignant of all brain tumors. Prognosis is poor, particularly if the tumor recurs after treatment. However, recent advances in molecular diagnosis have demonstrated that not all glioblastoma tumors are alike and some may respond differently to therapy.

Investigators at the Cleveland Clinic in Cleveland, Ohio reviewed the clinical course of 258 patients (median age = 62) with recurrent glioblastoma diagnosed between 2012 and 2017. They presented the results of their study at the American Academy of Neurology Annual Meeting in Los Angeles.

In the study, the researchers identified three glioblastoma subtypes among the participants: 66 (37%) had 06-methylguanin-DNA-methyltransferase (MGMT) methylation, 93 (44%) had epidermal growth factor receptor (EGFR) amplification, and 13 (6.9%) had isocitrate dehydrogenase (IDH) mutations.

Patients with MGMT methylation had a higher median overall survival of 15 months versus 10.8 months for the other subtypes (p < 0.001), explained Sushma Bellamkonda, MD, assistant professor of neurology at the University of Tennessee Health Science Center, Memphis, Tennessee, one of the study investigators. In addition, MGMT methylated patients had a longer median progression free survival (6.5 versus 3 months, p < 0.001) when treated with bevacizumab (Avastin) than with lomustine (Gleostine).

Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A), decreasing tumor angiogenesis. The ability of bevacizumab to inhibit new blood vessel growth has made it useful in the treatment of an assortment of tumors including colon, lung and renal. Bevacizumab received FDA approval in 2004 and is the oldest angiogenesis inhibitor available in the United States. Lomustine, an alkylating nitrosourea, is a more traditional chemotherapeutic agent.

Dr. Bellamkonda added that although progression free survival was higher with bevacizumab, total survival time was not increased. In other words, although the drug postponed time to recurrence, once the recurrence occurred, decline was rapid with no absolute gain in life expectancy.

Despite recent advances, prognosis remains grim for all patients with recurrent glioblastoma. However, the fact that tumor molecular subtype significantly influences overall survival and medication response provides a footing for future research for recurrent glioblastoma therapy. Clinicians who want their patients to have state-of-the-art care should refer patients to large cancer centers where tumor genotype testing and research protocols are available.