# Partial response to trastuzumab deruxtecan (DS8201) following progression in HER2-amplified breast cancer with pulmonary metastases managed with disitamab vedotin (RC48): a comprehensive case report and literature review

## TL;DR

A 42-year-old woman with HER2-positive breast cancer showed partial response to trastuzumab deruxtecan after progressing on disitamab vedotin, highlighting its potential in advanced cases.

## Contribution

Demonstrates the efficacy of trastuzumab deruxtecan in HER2-amplified breast cancer after ADC failure, combined with anti-PD-1 therapy.

## Key findings

- Trastuzumab deruxtecan (DS8201) induced partial remission after progression on disitamab vedotin (RC48).
- Combining DS8201 with tislelizumab enhanced anti-tumoral immune response and therapeutic efficacy.
- Long-term management of HER2-positive metastatic breast cancer is feasible with sequential ADC therapies.

## Abstract

Breast cancer remains one of the predominant malignancies worldwide. In the context of inoperable advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, systemic management primarily relies on HER2-targeting monoclonal antibodies. With the successful development of anti-HER2 antibody-drug conjugates (ADCs), these agents have been increasingly integrated into therapeutic regimens for metastatic breast cancer. Here, we present the case of a 42-year-old female patient with HER2-positive pulmonary metastatic breast cancer who underwent an extensive treatment protocol. This protocol included chemotherapy, radiation therapy, hormonal therapy, surgical intervention on the breast, and anti-HER2 therapies. The anti-HER2 therapies involved both singular and dual targeting strategies using trastuzumab and the ADC disitamab vedotin (RC48) over an 8-year period. After experiencing disease progression following HER2-targeted therapy with RC48, the patient achieved noticeable partial remission through a therapeutic regimen that combined trastuzumab deruxtecan (DS8201) and tislelizumab. The data suggest a promising role for DS8201 in managing advanced stages of HER2-amplified metastatic breast cancer, especially in cases that demonstrate progression after initial HER2-directed therapies using ADCs. Furthermore, its combination with anti-PD-1 agents enhances therapeutic efficacy by augmenting the anti-tumoral immune response.