Assessing patient burden and benefit: A decade of cabozantinib clinical trials

Drug development is complex and costly. Clinical trial participants take on risks, making it essential to maximize trial efficiency and maintain participant safety. Identifying periods of excessive burden during drug development can inform trial design, ensure patient benefit and prevent harm. This study aims to examine all published clinical trials for cabozantinib to assess patient benefit and burden over time. We conducted a retrospective cross-sectional review of interventional clinical trials of cabozantinib for solid cancer treatment. We searched PubMed/MEDLINE, Embase, Cochrane (CENTRAL) and . We extracted adverse event rates, median progression-free survival (PFS), median overall survival and objective response rate (ORR) for each included trial. We calculated frequencies of trial characteristics, cumulative grade 3-5 adverse event rates and cumulative ORRs. Out of 1735 studies, 54 publications were included that involved 6372 participants and 21 cancers. Of the 54 studies in our sample, 31 (57.41%) were single-arm trials and 23 (42.60%) had negative results. Trials among and within various indications had conflicting results over time. Cumulative risk to participants increased over time, and clinical benefit decreased. The findings suggest that the risk profile of cabozantinib increased from 2011 to 2016 and has remained elevated but stable while benefit has decreased over time. The use of non-randomized and single-arm trials is concerning, and more methodologically rigorous trials are needed. The results of trials for different indications are inconsistent, and empirical administration may reduce the drug's efficacy. Clinical trials are often viewed as opportunities for cancer patients to receive cutting-edge treatment. However, trials pose risks to patient safety, which potentially increase over time and frequently coincide with decreased benefits. Here, to better understand where clinical trials pose the greatest risks, the authors examined data from trials exploring cabozantinib for the treatment of solid tumors. Analyses show that out of 54 trials, 23 failed to meet pre-specified endpoints or employed an intolerable regimen. Most trials also were non-randomized, single-arm studies that potentially over-predict benefits. Inconsistency in the effectiveness of cabozantinib warrants careful consideration before further clinical study.image