2678 - Safety of Concurrent Administration of TDM1 and Radiotherapy in Patients with HER2+ Breast Cancer with Residual Disease Post-Neoadjuvant Chemotherapy

L. Girres¹, P. Torielli¹, E. Vigneau¹, L. Ettalhaoui¹, S. Guendouzen¹, J. Hotton¹, C. Jouannaud¹, A. Lemoine¹, P. Soibinet¹, D. Parent¹, S. Vignot¹, P. Guilbert¹, and A. Beddok²; ¹Institut Godinot, Reims, France, ²Department of Radiation Oncology, Institut Godinot, Reims, France

Purpose/Objective(s): This investigation assessed the safety, focusing on the risk of radiation-induced pneumonitis, of concurrent TDM1 and radiation therapy (RT) in non-metastatic HER2-positive breast cancer patients exhibiting residual disease after neoadjuvant chemotherapy. Materials/Methods: A retrospective cohort of 31 patients with HER2-positive, non-metastatic breast cancer, treated between April 2021 and September 2023 with TDM1 and concomitant locoregional RT, was analyzed. Toxicities were evaluated using the CTCAE v5.0. Lung computed tomography was performed for symptomatic patients to assess radiation-induced injury. The follow-up period extended from RT completion to the latest update. Statistical analysis was conducted using Chi-square or Fishers exact tests for categorical data and Mann-Whitney U for continuous variables, setting the significance threshold at p<0.05.

Results: The median age of the cohort was 63 years (IQR: 46-69), including nine smokers, of which five had not ceased smoking, and three with a history of chronic pulmonary disease (asthma, COPD). Neoadjuvant chemotherapy was administered to all, resulting in RCB scores =1 for each patient. The median RT dose was 50Gy (range: 50-50.4Gy), with 25 of 31 patients receiving lymph node irradiation and 22 receiving an additional tumor bed boost. The median PTV was 679.8 cc (IQR: 586.8-1079.9). The median mean dose to the ipsilateral lung was 13.4 Gy (IQR: 11.1-14.7), and the median V20 was 26% (IQR: 16-26). The median duration of TDM1 administration was 7.5 months (IQR: 6.75-8), with six patients continuing TDM1 at the time of data collection. The median time from TDM1 initiation to the start of RT was 32 days (IQR: 27-42 days), and the median duration of concurrent TDM1 and RT administration was 42 days (IQR: 38-48 days). No patient discontinued TDM1 due to RT. Grade =2 acute dermatitis was observed in 30% of patients (9/31). Grade =2 radiation pneumonitis occurred in 19.35% (6/31) within two months post-RT, necessitating early TDM1 cessation in one case. Univariate analysis identified a history of pulmonary disease as a significant risk factor for radiation pneumonitis (p=0.02), while mean dose to the ipsilateral lung and V20 did not significantly correlate with an increased risk of radiation-induced pneumonitis. After a median follow-up of 16 months post-RT (IQR: 6.5-26.5), grade =2 late toxicities were observed in 6.5% of patients.

Conclusion: Concurrent TDM1 and locoregional RT in HER2-positive breast cancer patients with residual disease post-neoadjuvant chemotherapy is feasible but associated with a notable risk of radiation pneumonitis. Detailed attention to patient history and careful monitoring during treatment are paramount for minimizing adverse outcomes.