Breast CancerTrastuzumab-deruxtecan and radiotherapy: a safety sub-analysis of combart prospective cohort study

Aim: This observational analysis, derived from the prospective mono-institutional COMBART cohort (stage IV breast cancer patients undergoing radiation therapy during novel systemic treatments), evaluates the safety of combining radiotherapy (RT) with Trastuzumab Deruxtecan (T-DXd) in metastatic breast cancer patients. Material and methods: Patients eligible for this analysis received conventional RT or stereotactic radiotherapy (SRT) concurrently with T-DXd. RT was considered concurrent if administered on the same day as T-DXd or during the 3-week interval between cycles. T-DXd was given at a dose of 5.4mg kg−1 via intravenous infusion every 3 weeks until progression or unacceptable toxicity. The primary endpoint was to assess RT-related acute and late toxicities, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Results: Forty patients who underwent RT or SRT concurrently with T-DXd were selected from the cohort of 145 patients enrolled in the COMBART trial. A total of 98 lesions were treated. Palliative RT was performed in 50.0% of patients, while 50.0% underwent SRT. Acute toxicity of any grade was observed in 8/40 patients (20.0%) during RT. One patient developed grade 3 anemia (3.3%), leading to RT discontinuation. Late toxicity occurred in 4/40 patients (10%) consisting of 3 radiation pneumonitis (RP) and 3 radionecrosis. Among the 22 patients treated with SBRT for oligoprogressive disease, the time from the initiation of RT to second disease progression (progression-free survival 2 -PFS2) was 11.3months (95% CI, 4.61-25.82), and the median time to systemic treatment change was 19.1months (95% CI, 12.7-25.56). Conclusions: The safety data for concurrent RT and T-DXd are promising. Most non-hematologic toxicities appear to be related to RT, while hematologic toxicities are likely influenced by T-DXd and should be closely monitored.