379P - Safety and efficacy of trastuzumab deruxtecan and concomitant radiation therapy in patients with metastatic breast cancer: A multicentre international retrospective cohort study

Background

Trastuzumab deruxtecan (T-DXd) has emerged as the standard treatment for patients with metastatic HER2-positive (HER2+) breast cancer (BC) following disease progression on first-line therapy containing taxanes and trastuzumab. Subsequently, results from the DESTINY-Breast04 have extended the approval of T-DXd to include HER2-low patients. Radiation therapy (RT) is often necessary in the metastatic setting, either for palliative purposes or with ablative intent. Our study aims to assess the safety of concurrent use of T-DXd and RT in a consecutive multicentre international cohort of BC patients.

Methods

We conducted a retrospective analysis of patients diagnosed with metastatic HER2+ or HER2-low BC, who were treated at three leading European Institutions. Patients started treatment with T-DXd between May 2021 and March 2024, with some receiving concomitant RT and others not. The primary objective of the study was to assess the association between RT administration and adverse events (AEs) greater than grade (G) 2.

Results

Data of 99 consecutive patients were retrospectively evaluated. Thirty-two patients received RT immediately before (within a month) or during T-DXd, for a total of 33 concomitant RT treatments, while 67 patients did not. Median age was 56 years old (range 34-88). The majority of patients (55.6%) received T-DXd as fourth or further line of systemic therapy. Median total RT dose prescription was 26 Gy (range 8-48) with a median number of fractions of 5 (range 1-15). Median EQD2 dose was 33 Gy (range 12-104) and median BED 39 Gy (14-125). The most frequently treated site was bone (43.8% of patients) followed by brain (37.5%). The relation between RT administration and the development of G2+ toxicity was not significant (p-value = 0.8). Grade 2 interstitial lung disease (IDL), that led to T-DXd discontinuation, was observed in one case in RT group (3.1%) and in three cases in no-RT group (4.5%). No radionecrosis events were observed among the 12 patients treated with intracranial RT.

Conclusions

Our preliminary data are encouraging regarding the potential safety of this combination, showing that concurrent RT did not increase severe acute toxicity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.