Comparison of efficacy of antibody drug conjugate (ADCs) between younger and older patients: A meta-analysis of phase 3 studies.

e15002 Background: Antibody-Drug-Conjugates (ADCs) are one of the new cornerstone of cancer treatments. New approvals are coming every year in various tumor types and settings. However, older adults remain underrepresented in clinical trials and consequently, few data is available for this population. Therefore, we performed a meta-analysis to compare the efficacy of ADCs between younger and older patients. Methods: PubMed and the ASCO or ESMO databases were searched up to December 2023. We included randomized controlled trials (RCTs) of ADCs (datopotamab deruxtecan, Enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan and trastuzumab deruxtecan) reporting subgroup comparison of overall survival (OS) and/or progression-free survival (PFS) based on age cutoffs. The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results: A total of 4654 patients from nine RCTs (ASCENT; DESTINY-Breast02, -Breast04, -Gastric01; EV-301, EV-302/KEYNOTE-A39; MIRASOL; TROPiCS-02 and TROPION-Lung01) were included. When patients are dichotomized into younger (N=2796) and older (N=1858) groups with an age cut-off of 65 years, ADCs improved OS in both younger (HR, 0.64; 95% CI, 0.52-0.80) and older (HR, 0.56; 95% CI, 0.44-0.71) groups. An improvement in PFS was observed in younger (HR, 0.55; 95% CI, 0.46-0.66) and older (HR, 0.52; 95% CI, 0.41-0.67) patients. Subgroup analyses according to ADCs and tumor type showed a consistent survival benefit in both younger and older groups. Conclusions: A benefit in OS with ADCs was significant in both younger and older patients with a cut-off age of 65 years. Prospective real life cohort study would be of interest to confirm those results with a description of geriatric parameters to better define the population.