[Therapeutic de-escalation strategies in the use of anti-PD-1 and anti-PD-L1: Dose, frequency, and duration].

Anti-PD1 and anti-PD-L1 inhibitors have become central to systemic therapy for solid tumors, reshaping indications and outcomes across multiple tumor types. Their widespread use, however, raises major economic, environmental, and societal challenges. Current regimens - fixed dose, defined frequency, and predetermined duration - are supported by limited clinical and paraclinical evidence. Consistent signals from pharmacokinetic and pharmacodynamic studies, retrospective cohorts and small prospective trials suggest that overtreatment is possible in a significant proportion of patients. In this context, therapeutic de-escalation should be evaluated along three axes: dose reduction, extension of dosing intervals, and adjustment of the total duration of treatment. This review summarizes the current state of knowledge on the pharmacokinetics and pharmacodynamics of checkpoint inhibitors, as well as retrospective and prospective clinical data exploring dose, frequency, and duration de-escalation across different tumor types. It also presents the main trials currently underway to evaluate these strategies and their clinical, economic, and societal impacts.