# Safety and effectiveness of post-trastuzumab deruxtecan regimens in patients with HER2-positive metastatic breast cancer who discontinued trastuzumab deruxtecan due to interstitial lung disease

## TL;DR

This study examines the safety and effectiveness of treatments after stopping trastuzumab deruxtecan in HER2-positive breast cancer patients due to lung issues.

## Contribution

The study provides real-world data on subsequent treatments after trastuzumab deruxtecan discontinuation due to interstitial lung disease in HER2-positive metastatic breast cancer patients.

## Key findings

- 81.5% of patients received anti-HER2 treatment after discontinuing trastuzumab deruxtecan due to ILD.
- Effectiveness outcomes were longest in patients with grade 1 ILD during prior trastuzumab deruxtecan treatment.
- Only 3.4% of patients experienced ILD recurrence during the first post-trastuzumab deruxtecan treatment.

## Abstract

The real-world EN-SEMBLE (jRCT1030220506) study investigated the effectiveness and safety of treatments subsequent to trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). This post hoc analysis provides informative data for subsequent treatment in patients who discontinue T-DXd due to interstitial lung disease (ILD).

Patients in EN-SEMBLE who discontinued T-DXd due to ILD were included in this analysis. Outcomes for first post-T-DXd treatment were real-world progression-free survival (rwPFS), real-world time to treatment failure (rwTTF), real-world time to next treatment (rwTTNT), and overall survival. ILD recurrence/exacerbation after initiating the first and second post-T-DXd treatments was evaluated.

This analysis included 146 patients. ILD grade during prior T-DXd treatment was 1, 2, 3, and unknown for 78 (53.4%), 46 (31.5%), 18 (12.3%), and 4 patients (2.7%), respectively. Most patients (81.5%) received subsequent anti-HER2 treatment. rwPFS was 7.2 months (95% confidence interval, 5.4, 10.2), rwTTF 6.5 months (5.1, 9.1), rwTTNT 7.8 months (5.9, 10.8), and overall survival 32.4 months (21.3, not estimable). These outcomes were numerically longer in patients with grade 1 versus 3 ILD during prior T-DXd treatment. Five patients (3.4%) had ILD recurrence during the first post-T-DXd treatment. Among the 93 patients who received second post-T-DXd treatment, 2 (2.2%) experienced ILD recurrence.

These findings highlight the importance of early ILD detection and management so patients can receive, and potentially benefit from, subsequent anti-HER2 targeted therapies. ILD recurrence/exacerbation during subsequent therapies was low in patients who experienced ILD with T-DXd.

•81.5% of patients received anti-HER2 treatment after discontinuing T-DXd due to ILD.•Effectiveness outcomes were longest in those with grade 1 ILD with prior T-DXd.•During the first post-T-DXd treatment, 5/146 patients (3.4%) had ILD recurrence.•This analysis highlights the importance of early ILD detection with T-DXd in mBC.

81.5% of patients received anti-HER2 treatment after discontinuing T-DXd due to ILD.

Effectiveness outcomes were longest in those with grade 1 ILD with prior T-DXd.

During the first post-T-DXd treatment, 5/146 patients (3.4%) had ILD recurrence.

This analysis highlights the importance of early ILD detection with T-DXd in mBC.