The trials of neuro-oncology clinical research

Glioblastoma (GBM) remains one of the most challenging and intractable of cancers. Despite being the initial focus of the national effort to identify the molecular driver(s) of solid tumors, these data failed to lead to the anticipated subgroup identification that would guide future clinical trials and therapeutics. Thus, the rationale and design of clinical trials for GBM have not changed that much in more than 50 years. If one examines the initial Brain Tumor Study Group trial (#69-01), which demonstrated the effectiveness of radiotherapy, one can see a sample size (303 patients) and endpoint (overall survival) that look frighteningly similar to modern studies of patients with newly diagnosed GBM.¹ In this issue of Neuro-Oncology, Vanderbeek et al examine our current clinical trial processes and how they are failing to advance only convincingly promising agents forward to phase III studies.² They do not suggest that the failure to identify better therapeutics rests solely with our flawed clinical trial system, and they state at the outset that only further scientific research will open new therapeutic avenues likely to be most helpful. However, they do highlight the wastefulness of our current clinical trial efforts—of time, effort, and patients—that ultimately fail to advance our mission toward improved outcomes.