Abstract PO3-22-06: Safety and efficacy of trastuzumab deruxtecan and concomitant radiation therapy in patients with metastatic HER2-positive breast cancer

Abstract Background 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 in the first line, which includes taxanes and trastuzumab. This recommendation is based on the results of the DESTINY-Breast03 trial, which demonstrated improved efficacy compared to trastuzumab emtansine (T-DM1). Radiation therapy (RT) is frequently required in the metastatic setting, either for palliative purposes or with ablative intent in cases of oligometastatic or oligoprogressive disease. The aim of our study is to evaluate the safety of using T-DXd and concomitant radiation therapy (RT) in a consecutive series of HER2+ BC patients. Methods We conducted a retrospective evaluation of patients diagnosed with metastatic HER2+ BC who initiated treatment with T-DXd between May 2021 and May 2023 at our institution, with or without receiving RT. We collected clinical data pertaining to the diagnosis of metastatic disease, T-DXd treatment, acute toxicities, survival data, and biological characteristics of both the primary tumor and metastases. The primary objective of this study was to assess the association between RT and any adverse events greater than grade (G) 2. Results We retrospectively evaluated data from 30 consecutive patients who were treated with T-DXd, with or without RT. Among these patients, ten received RT either immediately before (within a month) or during T-DXd treatment, while the remaining 20 did not. The median age of the patients was 72 years (range 34-88), and the median follow-up period was 9 months. Thirteen patients received T-DXd as the fourth or subsequent line of systemic anti-HER2 treatment, eight patients received it as the third line, and seven patients received it as the second line. Two patients, who experienced early metastatic disease relapse ( 6 months after completion of adjuvant anti-HER2 therapy), received T-DXd as their first-line treatment. The median prescribed total dose of RT was 34 Gy (range 20-48), with a median number of fractions of 4 (range 2-10). The median equivalent dose in 2 Gy fractions (EQD2) was 64 Gy (range 23.3-104), and the median biologically effective dose (BED) was 76 Gy (range 28-125). The most commonly treated sites were bone (70% of cases), followed by brain (20%) and liver (10%). A chi-square test of independence was conducted to examine the relationship between the administration of RT and the development of toxicity exceeding G2. However, this analysis did not reveal a significant relationship (p = .27). Regarding the specific toxicities of interest associated with T-DXd, three cases of grade 3 fatigue were reported in the group that did not receive RT, while one case was observed in the RT group. Overall, only one case of grade 3 nausea was reported, and it occurred in the group that did not receive RT. G2 interstitial lung disease, which led to discontinuation of T-DXd, was observed in one case in the RT group and one case in the no-RT group. Conclusions Our initial data is promising regarding the potential safety of this combination, as it indicates that concurrent RT did not lead to an increase in severe acute toxicity. However, larger series of data are required to validate and confirm these findings. Citation Format: Luca Visani, Carlotta Becherini, Niccolo' Bertini, Ilaria Bonaparte, Luca Burchini, Carolina Orsatti, Marianna Valzano, Marco Banini, Viola Salvestrini, Erika Scoccimarro, Vieri Scotti, Isacco Desideri, Giulio Francolini, Lorenzo Orzalesi, Marco Bernini, Cinzia Tommasi, Jacopo Nori, Simonetta Bianchi, Icro Meattini, Lorenzo Livi. Safety and efficacy of trastuzumab deruxtecan and concomitant radiation therapy in patients with metastatic HER2-positive breast cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-06.