Immunotherapy in older adults with gynecologic cancers: rethinking age as a limiting factor

As the global population ages, understanding immune checkpoint inhibitor (ICI) efficacy and safety in the older cancer patients is critical. ICIs represent a major advance, but their effectiveness relative to age-related immune changes warrants investigation. This review synthesizes current clinical and preclinical evidence examining how aging influences ICIs response. We discuss age-related immunological changes (immunosenescence), alterations in the tumor microenvironment, mechanistic insights from preclinical aging models, and clinical trial/real-world data on ICIs efficacy and safety including immune-related adverse events (irAEs) across various cancers in older patient, referencing meta-analyses and specific trial outcomes. Extensive clinical data suggest ICIs often provide significant survival benefits and are generally well-tolerated in appropriately selected older patients, with outcomes frequently comparable to younger cohorts, although efficacy can vary by tumor type, performance status (PS), and biomarkers. While irAEs require careful management considering comorbidities and frailty, overall incidence is not consistently higher in older adults. Treatment decisions should be individualized, integrating biological age indicators, PS, and comorbidities, rather than relying solely on chronological age. Future research should focus on identifying robust biomarkers and tailored strategies to optimize ICIs use in this demographic.