DDDR-85. Latest developments in GBM drug combination therapies for primary and recurrent GBM

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor characterized by diffuse invasion and disruption of nearby nervous tissue, resulting in a poor prognosis for many patients. Current standard of care therapy including maximal surgical resection followed by temozolomide (TMZ) chemotherapy and radiation has only modestly extended survival rates. However, recent investigations into combining TMZ with other therapeutic regimens has shown promising potential. In this study, we aimed to assess the clinical efficacy of combination drug therapies with diverse mechanisms of actions compared to the standard TMZ monotherapy. Primary outcomes included overall survival, progression-free survival, and adverse events (AE). Moreover, we examined usage trends and toxicity patterns associated with small molecule inhibitors (SMI). Using PRISMA guidelines, a systematic review was conducted. PubMed, Embase, Scopus, Cochrane Library, and Web of Science was searched for peer-reviewed articles published within the past five years that evaluated drug combination therapies in GBM. Studies were screened based on strict exclusion and inclusion criteria and key variables were extracted using the Covidence review manager. Of 147 eligible studies, TMZ, bevacizumab, and lomustine were the most frequently applied drugs in combination, presenting in 106 (72.1%), 43 (29.3%), 16 (10.9%) of studies, respectively. SMI utilization in combination therapies increased from 22.2% to 40% within the last five years. In addition, the most common classes of SMIs used were proteasome and tyrosine kinase inhibitors. Prevalent AEs related to drug combination therapies were fatigue, hypertension, and thrombocytopenia. Glioblastoma is a highly treatment-resistant malignancy that lacks curative treatment options. Conventional treatment standards have failed to significantly improve clinical outcomes. However, the combination of drug regimens along with SMIs has shown promising results that may guide future research efforts in treating this aggressive cancer.