# Antibody-drug conjugate (disitamab vedotin) therapy targeting HER2-low or higher advanced extramammary Paget’s disease

## TL;DR

A new antibody-drug conjugate targeting HER2 shows promising results in treating a rare and aggressive skin cancer called metastatic extramammary Paget’s disease.

## Contribution

Demonstrates the potential of disitamab vedotin as a targeted therapy for HER2-expressing metastatic extramammary Paget’s disease.

## Key findings

- 8 out of 11 patients (73%) showed objective response to disitamab vedotin treatment.
- Median progression-free survival was 5.5 months and median overall survival was 21.9 months.
- Treatment-related toxicity was mild, with no grade 3 or higher adverse events observed.

## Abstract

Metastatic Extramammary Paget’s disease (EMPD) is an extremely rare cancer and has a dismal prognosis. The rarity of metastatic EMPD has made the clinical trial almost unfeasible, thus high-quality retrospective analysis is valuable.

The electronic medical files of patients with metastatic EMPD treated from Jan 2017 to April 2024 in a tertiary cancer center in China were reviewed, and available tissues were collected for HER2 staining, if possible. Eleven patients were treated with the anti-HER2 antibody-drug conjugate Disitamab vedotin (DV), using doses of 2 mg/kg, once every 3 to 4 weeks. The efficacy and toxicity data were extracted. Key Findings and Limitations: Treatment with the antibody-drug conjugate DV elicited an objective response in 8 of 11 patients (73%), and CEA response in 10 of the 11 patients (91%). The median progression-free interval was 5.5 months. The median overall survival was 21.9 months. This efficacy was accompanied by mild grade 1 or 2 treatment-related toxicity and no grade 3 toxicity. This study is limited by a small sample size, retrospective nature, and inevitable selection bias. Conclusions and Clinical

Antibody-drug conjugate targeting of HER2 might be an active treatment for metastatic EMPD. We have initiated a clinical trial to confirm it prospectively.

Metastatic Extramammary Paget’s disease (EMPD) is an extremely rare cancer without standard treatment. Treatment with the antibody-drug conjugate DV (an anti-HER2 antibody-drug conjugate) elicited an objective response in 8 of the 11 patients (73%), and CEA response in 10 of the 11 patients (91%). This efficacy was accompanied by mild treatment-related toxicity. Antibody-drug conjugate targeting of HER2 might be an active treatment for metastatic EMPD.