Evaluating Risk Factors for Trastuzumab-Deruxtecan Pneumonitis in Patients With Metastatic Breast Cancer

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Abstract Rationale: Trastuzumab deruxtecan (T-DXd) treatment improved survival in HER2 positive and HER2-low metastatic breast cancer patients. However, treatment with T-DXd was associated with a significant risk of pneumonitis. Currently, there are no studies evaluating pre-treatment risk factors for T-DXd pneumonitis. To address this knowledge gap, we conducted a retrospective cohort study of breast cancer patients treated with T-DXd to identify potential risk factors for the development of T-DXd pneumonitis. Methods: Consecutive breast cancer patients who received at least one dose of T-DXd were included in this study. Pneumonitis was documented by the treating oncologist at the time of toxicity and retrospectively confirmed by a member of the study team. Pre-treatment variables of interest, including patient demographics, radiation dosimetry variables, and chest imaging abnormalities, were collected. Results: A total of 179 patients were included, and 23 (12.8%) developed T-DXd pneumonitis. Patients with pneumonitis had lower baseline oxygen saturation (98% vs 97%, p=0.02) and were more likely to have received Abemaciclib treatment (26.1% vs 9.6%, p=0.03) before T-DXd treatment. Pre-treatment chest imaging abnormalities (41.9% vs 47.8%, p=0.59) and prior treatment modalities, including prior immune checkpoint inhibitor treatment (16.0% vs 8.7%, p=0.50) and prior chest or breast radiation (61.5% vs 47.8%, p=0.20), were not associated with T-DXd pneumonitis. On multivariate analysis, neither pre-treatment chest imaging abnormalities nor prior chest or breast radiation were associated with T-DXd pneumonitis (OR 1.60 [0.62-4.20], p=0.33); OR 0.51 [0.20-1.33], p=0.17). There was no difference in overall survival in breast cancer patients with and without T-DXd pneumonitis (p=0.22). Conclusions: We found that pre-treatment chest imaging abnormalities, prior immune checkpoint inhibitor treatment, and prior chest or breast radiation did not increase the risk of T-DXd pneumonitis, while prior treatment with Abemaciclib may be a risk factor for T-DXd pneumonitis. Larger studies are needed to validate our results.

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