Abstract P2-10-06: Safety and efficacy of trastuzumab deruxtecan and concomitant radiation therapy in patients with metastatic breast cancer: a multicentre international retrospective cohort study

Abstract 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, as demonstrated by the findings of the DESTINY-Breast03 trial. 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 in cases of oligometastatic or oligoprogressive disease. Our retrospective 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 four leading European institutions. Patients started treatment with T-DXd between May 2021 and March 2024, with some receiving concomitant RT with palliative or ablative intent and others not. We defined ablative RT based on biological dose with threshold of minimum 50Gy EQD2(10) delivered in a maximum of 12 fractions, according to the EORTC and European Society for Radiotherapy (ESTRO) OligoCare (EORTC-1822-RP) study. The primary objective of the study was to assess the association between RT administration and adverse events (AEs) exceeding grade (G) 2. In all cases RT was administered within one month before Cycle 1 of therapy with T-DXd or during systemic treatment without any drug interruption. Results. Data of 118 consecutive patients treated with T-DXd with or without RT were retrospectively evaluated. Thirty-three patients received RT immediately before (within a month) or during T-DXd, for a total of 34 concomitant RT treatments, while 85 patients did not. Median age was 55 years old (range 30-88). At a median follow up of 18 months (range 1-33), 8 patients (24.2%) had died in the RT group and 17 patients (20.0%) in the no-RT group. Sixty-two patients (52.5%) received T-DXd as fourth or further line of systemic therapy, while 38 (32.2%) in third line and 15 (12.7%) in second line. Three patients (2.6%) with early metastatic disease relapse (<6 months after adjuvant anti-HER2 therapy completion) received T-DXd as first line treatment. Median total RT dose prescription was 34Gy (range 8-48) with a median number of fractions of 4 (range 1-15). Median EQD2 dose was 64Gy (range 12-104) and median BED 76Gy (14-125). The most frequently treated site was central nervous system (51.5%; n=17/33), followed by bone (33.3%; n=11/33). Fifteen patients received RT with ablative intent (45.5%), 18 patients RT with palliative intent (54.5%). 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=0.79; significance level p<0.05). Regarding toxicities of special interest for T-DXd, 3 cases of G3 fatigue have been reported in no-RT group (3.5%) with 1 case in the RT group (3.0%). Overall, only 1 case of G3 nausea was observed (in the no-RT group). Grade 2 interstitial lung disease (IDL) or G2-3 pneumonitis were observed in 4 cases in RT group (12.1%) and in 8 cases in no-RT group (9.4%). No radionecrosis events were reported among the 17 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. Data from larger series are needed to confirm these results. Citation Format: Luca Visani, Ivica Ratosa, Barbro Linderholm, Rupert Bartsch, Domen Ribnikar, Jacopo Scialino, Niccolò Bertini, Ilaria Bonaparte, Dimitar Stefanovski, Nika Dobnikar, Magdalena Sojar, Angelika Starzer, Isacco Desideri, Chiara Mattioli, Cecilia Petruccioli, Jacopo Nori, Lorenzo Orzalesi, Simonetta Bianchi, Marianna Valzano, Viola Salvestrini, Carlotta Becherini, Lorenzo Livi, Icro Meattini. Safety and efficacy of trastuzumab deruxtecan and concomitant radiation therapy in patients with metastatic breast cancer: a multicentre international retrospective cohort study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-10-06.