ADC Efficacy in Metastatic Breast Cancer Appears Similar by Age

A systematic review and meta-analysis of 20 randomized trials assessed antibody-drug conjugates (ADCs) in breast cancer, including 13,055 participants, 18% of whom were aged 65 or older. In metastatic disease, ADCs improved progression-free survival in both age groups, but age-stratified safety data were too limited for meaningful comparison.

Metastatic PFS benefit was similar across age groups.
No significant age-by-treatment interaction was found.
Age-stratified safety data were insufficient.
Early-stage results could not be pooled.

Researchers searched three databases through November 17, 2025, for phase 2 or 3 randomized trials comparing ADCs with non-ADC therapies in early-stage or metastatic breast cancer. The review included 20 trials and 13,055 participants: 14 metastatic-disease trials and six early-stage trials. Outcomes included progression-free survival (PFS), invasive disease-free survival, overall survival and grade 3 or higher adverse events (AEs), with results examined by age (65 years or older versus younger than 65).

In metastatic disease, ADCs improved PFS in both older participants (pooled hazard ratio [pHR], 0.64; 95% CI, 0.51–0.79) and younger participants (pHR, 0.58; 95% CI, 0.51–0.66). The age-by-treatment interaction was not significant (ratio of hazard ratios, 1.10; 95% CI, 0.91–1.33). ADCs also improved overall survival in metastatic disease, but no trial reported age-stratified overall-survival results. Early-stage findings could not be pooled: only two trials reported age-stratified invasive disease-free survival, with discordant results.

The findings suggest similar metastatic PFS benefit across age groups, but do not resolve safety in older adults. Although grade 3 or higher AEs were reported in all trials, only three provided age-stratified data, and none reported toxicity jointly by age and treatment arm. Older adults made up 18% of participants, further limiting the evidence base for this group.

In practice

For adults aged 65 years or older with metastatic breast cancer, this meta-analysis found PFS benefit with ADCs comparable to that in younger trial participants, with no significant age-by-treatment interaction. These results suggest age alone did not modify the relative PFS benefit in the included trials, but they do not establish that ADC toxicity is comparable in older and younger adults: only three trials reported age-stratified grade 3 or higher adverse events, and none stratified toxicity by both age and treatment arm. Evidence for early-stage disease was also limited.

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Source

JNCI: Journal of the National Cancer Institute: Efficacy and toxicity of antibody-drug conjugates in older adults with breast cancer: A systematic review and meta-analysis ↗

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