News|Articles|March 6, 2026

Enhertu Tolerable in Patients With HER2-Low Metastatic Breast Cancer

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Key Takeaways

Toxicity-related discontinuation occurred in 15%, largely ILD/pneumonitis, mirroring DESTINY-Breast04, supporting generalizability of trastuzumab deruxtecan tolerability to community practice populations.
Adverse-event burden was dominated by fatigue (79.3%), nausea/vomiting (73%), diarrhea (45%), anemia (29.7%), and ILD/pneumonitis (10%), with additional hematologic and cardiac signals including neutropenia and LVEF reduction.
ILD/pneumonitis management most often used corticosteroids (80%) and frequently required discontinuation (66.7%) and treatment holds/delays (56.7%), underscoring the need for early recognition and intervention pathways.
Treatment holds/delays and dose reductions were commonly deployed for nausea/vomiting, neutropenia, fatigue, diarrhea, anemia, thrombocytopenia, and LVEF decline, reflecting multidimensional toxicity mitigation in routine care.
Cohort characteristics showed later-line utilization (only 3.7% first-line; 23.7% sixth+ line), median two prior endocrine lines, 39.3% comorbidity prevalence, and predominantly HR-positive disease (77%).

New data show that Enhertu had similar safety in the real world as in clinical trials in patients with HER2-low metastatic breast cancer.

Real-world data show that Enhertu (fam-trastuzumab deruxtecan-nxki) was tolerated as well in the community setting, where patients had higher disease burden, as in the clinical trial setting, according to data shared at the 43rd Annual Miami Breast Cancer Conference.

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 the DESTINY-Breast04 trial. 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.

MEOIs included fatigue (79.3%), nausea or vomiting (73%), diarrhea (45%), anemia (29.7%), alopecia (16.3), respiratory infection (16.3%), neutropenia (13.3%), rash (10.7%), ILD/pneumonitis (10%), stomatitis (8.3%), thrombocytopenia (6.7%), blurred vision (5%), reduced left ventricular ejection fraction (5%), 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.

Enhertu was discontinued for 20 patients with ILD/pneumonitis; five each with fatigue or reduced left ventricular ejection fraction; four with anemia; three each with nausea/vomiting or diarrhea; two each with stomatitis or febrile neutropenia and one each with respiratory infection, neutropenia, rash and thrombocytopenia.

Treatment was held or delayed for 17 patients with ILD/pneumonitis, 11 each with nausea/vomiting and neutropenia, 10 with fatigue, nine with diarrhea, eight each with anemia and reduced left ventricular ejection fraction, seven with thrombocytopenia, six with respiratory infection and one with rash.

Dose reductions were used to manage toxicity in 14 patients with neutropenia, 13 with nausea/vomiting, 12 with fatigue, seven each with diarrhea and anemia, four with thrombocytopenia, two with ILD/pneumonitis and one each with blurred vision or respiratory infection.

Corticosteroids were used most frequently to manage ILD/pneumonitis events (80%), followed by treatment discontinuation (66.7%), treatment hold or delay (56.7%), other supportive care intervention (33.3%), antibiotics (23.3%), hospitalization (20%), emergency department visit (10%), unscheduled clinic visit (10%) 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 Enhertu 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 Enhertu, 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% of patients had hormone receptor-positive disease, 39.3% had at least one comorbidity, 33% had stage 2 disease, 24.7% had stage 4, 19.7% had stage 3, 12.3% had stage 0 to 1 and 10.3% had no stage recorded. Performance status at baseline was not impaired for 72%. Patients had a median of two prior lines of endocrine therapy and a mean follow-up of 12.6 months.

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, and 98.7% were female sex. Most patients (79.7%) were White, 5% were Black or African American and 15.3% were of another race or did not have race recorded.

References

“Real-world safety of trastuzumab deruxtecan in HER2-low metastatic breast cancer: insights from US community oncology practices” by Mark Walker, et al. Presented at the 43^rd Miami Breast Cancer Conference; March 5-8, 2026.
“Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer” by Dr. Shanu Modi, et al. New England Journal of Medicine.

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