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 5.4 mg 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 11.3 months (95% CI, 4.61-25.82), and the median time to systemic treatment change was 19.1 months (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.