192P Safety and efficacy of trastuzumab deruxtecan and concomitant radiation therapy in patients with metastatic HER2-positive breast cancer

Trastuzumab deruxtecan (T-DXd) currently represents the standard of care for the treatment of patients with metastatic HER2-positive (HER2+) breast cancer (BC) after disease progression to first-line containing taxanes and trastuzumab. Radiation therapy (RT) is frequently required in the metastatic setting, either with palliative or ablative intent. The aim of our study is to evaluate the safety of the use of T-DXd and concomitant RT in a consecutive series of HER2+ BC patients. We retrospectively evaluated patients diagnosed with metastatic HER2+ BC, treated at two leading European institutions, who started treatment with T-DXd between May 2021 and August 2023, receiving RT or not. The primary outcome of the study was the association between RT and any adverse events (AEs) > grade (G)2. Data of 52 consecutive patients were retrospectively evaluated. Sixteen patients received RT immediately before (within a month) or during T-DXd, for a total of 17 RT treatments, while 36 patients did not. Median age was 54 years old (range 34-88). Twenty-one patients (40.4%) received T-DXd as fourth or further line of systemic anti-HER2 treatment, while 16 (30.8%) in third line and 13 (25.0%) in second-line. Median total RT dose prescription was 30 Gy (range 8-48) with a median number of fractions of 3 (range 1-15). Median EQD2 dose was 50 Gy (range 16-104) and median BED 60 Gy (24-149). The most frequently treated site was bone (47.1% of cases; N=8/17). A chi-square test of independence was performed to examine the relation between RT administration and the development of >G2 toxicity. The relation between these variables was not significant (p = 0.83). Regarding toxicities of special interest for T-DXd, only 1 case of G3 nausea was observed (in the no-RT group). Grade 2 interstitial lung disease (IDL), that led to T-DXd discontinuation, was observed in 1 case in RT group and in 2 cases in no-RT group. No radionecrosis events were observed among the 4 patients treated with intracranial RT. Our first data are encouraging regarding the potential safety of this combination, showing that concurrent RT did not increase severe acute toxicity. Data from larger series are needed to confirm these results.