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

Breast. 2025 Apr:80:104421. doi: 10.1016/j.breast.2025.104421. Epub 2025 Feb 13.

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.

Keywords: Combined therapy; Efficacy; Radiotherapy; Safety; Trastuzumab deruxtecan.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / therapy
  • Camptothecin / analogs & derivatives
  • Chemoradiotherapy* / adverse effects
  • Chemoradiotherapy* / methods
  • Female
  • France
  • Humans
  • Immunoconjugates
  • Middle Aged
  • Receptor, ErbB-2 / metabolism
  • Retrospective Studies
  • Trastuzumab* / administration & dosage
  • Trastuzumab* / adverse effects
  • Trastuzumab* / therapeutic use
  • Treatment Outcome

Substances

  • Trastuzumab
  • Receptor, ErbB-2
  • trastuzumab deruxtecan
  • ERBB2 protein, human
  • Antineoplastic Agents, Immunological
  • Camptothecin
  • Immunoconjugates