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. 2025 Feb 3;27(1):16.
doi: 10.1186/s13058-025-01967-1.

Evaluating risk factors for Trastuzumab-Deruxtecan Pneumonitis in patients with metastatic breast cancer

Jonathan Henricks #  1 , Tyler Haddad #  2 , Omair Ahmed  1 , Jonathan Schoenhals  3 , Pavnesh Kumar  3 , Ryan Wilson  4 , Jianing Ma  5 , Jing Gennie Wang  2 , Michael Wert  2 , Vincent Esguerra  2 , Ian Bentley  2 , Kai Johnson  6 , Daniel Stover  6 , Sachin R Jhawar  3 , Margaret Gatti-Mays  6 , Kevin Ho  7   8
Affiliations

Evaluating risk factors for Trastuzumab-Deruxtecan Pneumonitis in patients with metastatic breast cancer

Jonathan Henricks et al. Breast Cancer Res. .

Abstract

Background: Trastuzumab deruxtecan (T-DXd) is FDA-approved for treatment of patients with HER2 positive and HER2-low metastatic breast cancer. Currently, there is limited understanding of pre-treatment risk factors for pneumonitis associated with T-DXd.

Methods: Consecutive breast cancer patients who received at least one dose of T-DXd at a single academic cancer study between January 1, 2019, and February 20, 2024, were identified for analysis. Pneumonitis was documented by the treating oncologist at the time of toxicity and retrospectively independently confirmed by a member of the study team through chart and radiologic review. Pre-treatment variables of interest were collected, including patient demographics, radiation dosimetry variables, and chest imaging abnormalities.

Results: Of 179 total patients, 23 (12.8%) had pneumonitis after T-DXd exposure. Patients with pneumonitis had lower baseline oxygen saturation (98% vs. 97%, p = 0.02) and were more likely to have received abemaciclib (26.1% vs. 9.6%, p = 0.03) before T-DXd. Multiple pre-treatment variables were not found to be associated with T-DXd pneumonitis, including chest imaging abnormalities (41.9% vs. 47.8%, p = 0.59), 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). On multivariate analysis, prior treatment with abemaciclib remained significantly associated with T-DXd pneumonitis (OR 3.25 [1.07-9.11], p = 0.04), while neither pre-treatment chest imaging abnormalities nor prior chest or breast radiation were associated (OR 1.60 [0.62-4.20], p = 0.33); OR 0.51 [0.20-1.33], p = 0.17).

Conclusions: In this cohort, prior treatment with abemaciclib may be a risk factor for T-DXd pneumonitis. Conversely, 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. Larger studies are warranted to validate these findings toward an improved understanding of risk factors for pneumonitis after T-DXd exposure.

Keywords: Breast cancer; Pneumonitis; Trastuzumab-Deruxtecan.

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Conflict of interest statement

Declarations. Ethics statement: The study protocol was reviewed and approved by The OSU Institutional Review Board (2023C0104), and a waiver of informed consent was granted due to the retrospective nature of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Survival difference between those with and without pneumonitis
Fig. 2
Fig. 2
Survival difference between mild and severe pneumonitis
See this image and copyright information in PMC

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