Safety and efficacy of combined trastuzumab-deruxtecan and concurrent radiation therapy in breast cancer. The TENDANCE multicentric French study

Abstract

Purpose

Trastuzumab Deruxtecan (T DXD), a new antibody drug conjugate is a new treatment option for 2nd line metastatic breast cancer (MBC) for HER2 + or HER2 low tumors. Palliative or ablative radiotherapy (RT) may be required in patients who are being treated with T-DXd. However there is a lack of evidence regarding the safety profile of combining T-DXd with RT. TENDANCE study aimed to evaluate safety and efficacy of combined T-DXd and RT.

Materials and methods

This retrospective multicenter study included 54 patients treated concurrently with T-DXd and RT for HER2+ and HER2 low MBC between February 2021 and December 2023. All data were collected from a web-questionnaire, centralized after medical records and validation of the protocol by the local ethical committee. Primary endpoint was the safety of combined therapy.

Results

Median age was 60 years. Patients who received T-DXD were further categorized into HER2+ (40.7 %), HER2 low/hormonal receptors HR+ (40.8 %) or HER2 low/HR- (18.5 %). In the HER2+ patients, T-DXd was administered as 2nd (18.2 %) or 3rd (31.8 %) or 4th (50 %) line therapy. RT was delivered using palliative (72.2 %) or ablative doses (27.8 %). Indications consisted mostly of palliative bone irradiation (46.3 %) and stereotactic radiosurgery (SRS) (25.9 %). With the median follow-up of 9 months, 22.2 % of patients had a complete response and 77.8 % had either a partial response or stable disease. Grade 1 or 2 asthenia was observed in 51.8 % of patients, while only 16.6 % experienced other grade 1 or 2 adverse effects. There was no T-DXd therapy discontinuation related to RT.

Conclusion

To our knowledge, TENDANCE is the largest study evaluating concurrent T-DXd and RT. This preliminary report suggests the feasibility of the combination of RT and T-DXd with manageable toxicity rate. Longer follow-up and further prospective studies are required to confirm these results.