Despite the abundance of approvals and launches of novel therapies in the oncology space, glioblastoma multiforme (GBM), a solid tumor type, has had no new drugs to market since the approval of Genentech’s Avastin (bevacizumab) in 2009. Key opinion leaders (KOLs) have shared their views and insight into why late-stage agents do not make it through to approval for this aggressive form of brain cancer.

Historically, developers have found it challenging to formulate novel agents for GBM due to the blood brain barrier limitation and difficulty in designing reliable early-stage trials. KOLs interviewed by GlobalData noted that patients selected for early-stage GBM trials are screened meticulously and are carefully selected so that only the fittest and most motivated patients are included, while patients with a poor prognosis are excluded. Therefore, the survival data from trials appears better than real-world data, which has led to many to randomised Phase III trials being initiated with insufficient evidence.

KOLs have also noted that developing drugs in the recurrent setting is particularly challenging; magnetic resonance imaging scans are hard to interpret, making it difficult to determine a clear response. Furthermore, unless the study is randomised, overall survival and progression-free survival endpoints are completely meaningless because they only apply to the specific subset of patients that entered the study. Therefore, experts explained that primary endpoints in clinical trials need to be based on the response rate of the drugs, otherwise the study is comparing underlying prognosis factors within a particular cohort of patients to irrelevant historical data. The misinterpreted early-stage data has made KOLs very skeptical of new results in the field.

Taking new therapies for GBM to market has been challenging due to difficulties in demonstrating a clear benefit for patients. However, once early-stage trials are powered in a more effective way, Phase III trials will have the chance to show benefit. Developers in the GBM space will need to focus on overcoming these setbacks when constructing clinical trials in order to push their pipeline agents through to the finish line.