e24017 Background: Conducting geriatric trials is the most feasible way to address the vast underrepresentation of older adults in clinical trials of cancer therapies. This study is a globally comprehensive examination of geriatric cancer drug trials worldwide over the last decade. Methods: Up-to-date information on cancer drug trials in older adults aged over 59 years from the beginning of 2012 to the end of 2021 was collected from Trialtrove and Pharmaprojects. The number of identified trials was the dependent variable and corresponding analysis was conducted from the perspective of time trend, status quo and comparisons by region and country, sponsor type and cancer type, study status and phase. Results: 582 geriatric cancer drug trials were identified, with 292 trials for solid cancer while the other 290 trials were for hematological malignancies. Among them, 307 were single-region studies, 407 were initiated by academic groups, and 96 were terminated. Decreasing trends in the annual number of all trials (-3.8% per year) were observed over time, especially in solid tumor (-9.2% per year). For all these trials, 303 were conducted in Asia; this number was significantly higher than that in Europe (174), North America (129), Oceania (27) and South America (8). Similar difference was found in participation rate in trials by academic groups ranging from 59.5% in Asia to 0.5% in South America. In terms of development time, 86 and 176 were initiated before drug and indication approval, respectively, and the remaining 320 were initiated after indication approval. Phase II trials accounted for the highest proportion of trials (68.4%), while phase I trials accounted for the lowest proportion (7.2%). Compared with the hematological malignancies, trials on solid tumor had a higher terminated rate(18.8% vs 14.1%, p= 0.032) and were less likely to initiated before drug approval(6.5% vs. 23.1%, p< 0.0001) . Treatment was explored for 21 different cancers, with leukaemia, lung cancer and lymphoma being the most common. Conclusions: Geriatric trials of cancer drugs are scarce and partially prematurely terminated. Moreover, the number of geriatric trials has decreased and differs according to region. Global guidance and regulatory supervision are needed to facilitate the acquisition of adequate evidence on drug risk-benefit profiles in older adults, and thus to achieve high-quality care and safe medication. [Table: see text]

Unblinding at disease progression in double-blinded randomized controlled cancer drug clinical trials is ethical to the patient by ensuring optimal subsequent treatment, but the effect of study treatment on overall survival may be confounded. The views of science and ethics in this issue are controversial and the unblinding procedures should be well-designed. In real world settings, a lack of use of this unblinding process in protocol was observed in the analysis of 134 double-blind randomized controlled anticancer drug clinical trials conducted in China from 2018 to 2021. Unblinding at disease progression was allowed in only 26 (18.2%) trials. Among them, Only 9 (34.6%) trials involved patient-level unblinding. None of the 134 included trials accounted for the risk of blind-maintenance after disease progression. Based on the analysis and case studies, we believe that unblinding at disease progression should be stated in the protocol when the treatment assignment directly affected the choice of subsequent regimen, in which the drug category, control group design, standard of care of further-line therapy and primary endpoint together play a role. When unblinding at disease progression is adopted, the sensitivity analytics are recommended to understand the true effect of study drug on overall survival. The notification of treatment allocation after unblinding and the informed consent also require attention. A decision-making framework is established to help understand this controversy, which should be carefully discussed by the investigator and the sponsor.