Efficacy and toxicity of antibody-drug conjugates in older adults with breast cancer: a systematic review and meta-analysis
A partir d'une revue systématique de la littérature publiée jusqu'en novembre 2025 (20 essais), cette méta-analyse évalue l'efficacité, du point de vue de la survie sans progression et de la survie sans maladie invasive, et la toxicité des conjugués anticorps-médicaments chez les patientes âgées atteintes d'un cancer du sein (âge : supérieur ou égal à 65 ans)
Background: Antibody-drug conjugates (ADCs) have reshaped breast cancer treatment, yet their efficacy and toxicity in older adults (≥65 years) remain poorly characterized.
Methods: We searched PubMed, Ovid MEDLINE, and Embase (Elsevier) through November 17, 2025 for phase 2 or 3 randomized trials comparing ADCs versus non-ADC therapies in metastatic or early-stage breast cancer. The primary analysis assessed progression-free survival (PFS) in metastatic disease and invasive disease-free survival (IDFS) in early-stage disease, stratified by age (≥65 vs. <65 years), using pooled hazard ratios (pHRs). Age-by-treatment interaction was assessed using the ratio of HRs. Secondary outcomes included overall survival (OS) and grade ≥3 adverse events (AEs).
Results: Of 3,045 records identified, 20 trials (14 metastatic, 6 early-stage; 13,055 participants, 18% aged ≥65 years) met inclusion criteria. In metastatic trials, ADCs improved PFS in both older (pHR, 0.64; 95% CI, 0.51–0.79) and younger participants (pHR, 0.58; 95% CI, 0.51–0.66), with no significant age-by-treatment interaction (pooled ratio of HRs, 1.10; 95% CI, 0.91–1.33). ADCs also improved OS in the metastatic setting, though no trial reported age-stratified OS. In early-stage trials, only two reported age-stratified IDFS, with discordant results precluding pooled analysis. Grade ≥3 AEs were reported across all trials, but only three provided age-stratified data, and none stratified AEs jointly by treatment arm and age.
Conclusion: ADC efficacy in metastatic breast cancer was similar across age groups, though data in early-stage disease were limited. Insufficient age- and treatment-stratified toxicity reporting precludes meaningful safety assessment of ADCs in older adults with breast cancer.
Journal of the National Cancer Institute , résumé, 2026