News|Articles|March 9, 2026
Real-World T-DXd Safety in HER2-Low Metastatic Breast Cancer Confirmed
Author(s)Bridget Hoyt
Fact checked by: Ariana Pelosci
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Key Takeaways
- Toxicity-related T-DXd discontinuation was 15%, closely aligning with DESTINY-Breast04 (16.2%), supporting feasibility of administration in community oncology despite higher real-world disease burden.
- ILD/pneumonitis occurred in 10.0% (vs 12.1% in DESTINY-Breast04) and was the leading driver of discontinuation; management commonly included corticosteroids, holds/delays, and hospitalization.
Real-world community study finds Enhertu in HER2-low metastatic breast cancer has trial-like discontinuation rates; ILD remains key toxicity.
A real-world cohort of patients with HER2-low metastatic breast cancer receiving trastuzumab deruxtecan (T-DXd; Enhertu) in community oncology settings showed similar rates of discontinuation due to toxicity as was seen in the phase 3 DESTINY-Breast04 (NCT03734029) trial, despite higher disease burdens in the real-world cohort, demonstrating its feasibility in community settings, according to data shared at the 43rd Annual Miami Breast Cancer Conference.1,2
Total treatment discontinuation due to toxicity was 15%, most of which were due to interstitial lung disease (ILD)/pneumonitis, which is comparable to the 16.2% reported in DESTINY-Breast04.1,2 Medical events of interest (MEOI) or all grades during and up to 30 days after the start of T-DXd treatment was the study’s end point.1
MEOIs included fatigue (79.3%), nausea or vomiting (73.0%), diarrhea (45.0%), anemia (29.7%), alopecia (16.3), respiratory infection (16.3%), neutropenia (13.3%), rash (10.7%), ILD/pneumonitis (10.0%), stomatitis (8.3%), thrombocytopenia (6.7%), blurred vision (5.0%), reduced left ventricular ejection fraction (5.0%), febrile neutropenia (1.7%), new or worsening congestive heart failure (1.3%), and infusion reaction (0.3%). Of note, 12.1% of patients in DESTINY-Breast04 had ILD/pneumonitis.2
T-DXd was discontinued for 20 patients with ILD/pneumonitis; 5 each with fatigue or reduced left ventricular ejection fraction; 4 with anemia; 3 each with nausea/vomiting or diarrhea; 2 each with stomatitis or febrile neutropenia; and 1 each with respiratory infection, neutropenia, rash, and thrombocytopenia.1
Treatment was held or delayed for 17 patients with ILD/pneumonitis, 11 each with nausea/vomiting and neutropenia, 10 with fatigue, 9 with diarrhea, 8 each with anemia and reduced left ventricular ejection fraction, 7 with thrombocytopenia, 6 with respiratory infection, and 1 with rash.
Dose reductions were used to manage toxicity in 14 patients with neutropenia, 13 with nausea/vomiting, 12 with fatigue, 7 each with diarrhea and anemia, 4 with thrombocytopenia, 2 with ILD/pneumonitis, and 1 each with blurred vision or respiratory infection.
Corticosteroids were used most frequently to manage ILD/pneumonitis events (80.0%), followed by treatment discontinuation (66.7%), treatment hold or delay (56.7%), other supportive care intervention (33.3%), antibiotics (23.3%), hospitalization (20.0%), emergency department visit (10.0%), unscheduled clinic visit (10.0%), and dose reduction (6.7%).
Methods and Patient Characteristics
The retrospective observational study collected data from structured and unstructured electronic health record data curated through human review by the ONCare Alliance. The review included 300 randomly sampled adult patients with HER2-low metastatic breast cancer who began treatment with T-DXd in any progression-based line of therapy after metastatic diagnosis.
Data were collected from the time of diagnosis through the end of follow-up, occurring at whichever came first of the end of the line of therapy following T-DXd, end of patient record, or death. Descriptive statistics were used to inventory baseline characteristics, MEOIs, and actions taken to manage MEOIs.
Regarding disease burden and staging, 77.0% of patients had hormone receptor-positive disease, 39.3% had at least 1 comorbidity, 33.0% had stage II disease, 24.7% had stage IV, 19.7% had stage III, 12.3% had stage 0 to I, and 10.3% had no stage recorded. Performance status at baseline was not impaired for 72.0%. Patients had a median of 2 prior lines of endocrine therapy (IQR, 1-3) and a mean follow-up of 12.6 months (SD, 8.0).
Only 3.7% received T-DXd in the first line of therapy, while 23.7% received it in the sixth or later line, 23.3% received it in the third line, 20.3% received it in the fourth line, 15.7% received it in the second line, and 13.3% received it in the fifth line.
Patients included in the study had a mean age of 63.5 years (SD, 12.1), and 98.7% were female sex. Most patients (79.7%) were White, 5.0% were Black or African American, and 15.3% were of another race or did not have race recorded.
REFERENCES
1. Walker M, Nguyen M, Shah R, et al. Real-world safety of trastuzumab deruxtecan in HER2-low metastatic breast cancer: insights from US community oncology practices. Presented at the 43rd Miami Breast Cancer Conference; March 5-8, 2026.
2. Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
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