Clrm-18 screen failures in phase iii glioblastoma clinical trials

Abstract Glioblastoma (GBM) remains the most common and lethal malignant primary brain tumor in adult patients, with median overall survival ranging from 7 to 22 months. National Comprehensive Cancer Network guidelines encourage participation in clinical trials for both newly diagnosed and recurrent GBM patients. Multiple phase II trials in GBM have yielded promising, positive results, but the translation to phase III results is lacking and has failed to make strides in improving outcomes. These phase III trials universally require many participants, and the expenditure of phase III clinical trials is quite significant, with the median being 21.4 million dollars. With a paucity of ground-breaking phase III clinical trials and the cost expenditure to perform them, understanding screen failures in GBM clinical trials along with an evaluation of causes of screen failures is warranted. Using both ClinicalTrials.gov and PubMed, phase III clinical trials in GBM patients published from 1994 to 2021 were queried. This search, initially in ClinicalTrials.gov, involved using the terms: “glioblastoma” and “GBM” with filters “phase III,” “interventional,” “completed,” “suspended,” and “terminated.” This search was cross-referenced with PubMed for published full articles in English peer-reviewed journals. Fifty-one studies were identified, and 21 out of 51 were appropriate for evaluation of screen failures, with 15 being for newly diagnosed GBM and six being for recurrent GBM. Nine out of 21 (42.9%) did not publish information on screen failures, and in the remaining 12 studies, proportions of screen failures ranged from 0-84.0% for newly diagnosed studies and 9.2-23.2% for recurrent studies, with a combined median percentage of 28.9%. In this analysis, over one-fourth of patients screen failed for GBM clinical trials. Thus, it is prudent to explore the causes of these screen failures, their implications on clinical trial design, and their impact on patient outcomes clinically, financially, and holistically.