Age and frailty in anticancer drug regulatory assessment: a comprehensive cohort study of European marketing authorisations 2012-2023.

Background: Prevalence of cancer increases with age, but older adults remain underrepresented in pivotal clinical trials. We analysed the representation of older adults and poor performance score patients in initial marketing authorisation (MA) of new anticancer medicines in the European Union (EU). Materials and methods: Medicines with an anticancer indication authorised in the EU during the years 2012-2023 were analysed based on public assessment reports (EPARs). We identified original clinical studies and datasets based on the classification in the EPARs. Results: One hundred and thirty-seven products and MAs, corresponding with 153 efficacy datasets fulfilled the inclusion criteria. Most studies had enrolled subjects in age groups 65-74, 75-84, and ≥85 years of age; however, the proportion of individuals in these age groups was low. The majority of cases analysed efficacy in patient subgroups of >65 years of age, whereas a minority of studies evaluated efficacy for groups older than 70 years. No differences were observed between time cohorts from 2012-2017 and 2018-2023. Fifty-one percent of datasets allowed inclusion of patients with an Eastern Cooperative Oncology Group performance status of ≥2, whereas the median proportion of these patients was 1.8%. Safety was specifically analysed in subjects of >65 years of age in 92% of MAs. A dedicated discussion on age and/or frailty was identified in 45% of the MAs. Age- or frailty-related Annex II conditions were found in 10 cases. Conclusion: Older adults and patients with higher performance scores have been included in the pivotal MA data and analyses, but their proportions have remained low. An opportunity for structured communication on age-related uncertainties is identified.