A real-world cohort analysis presented at the 43rd Annual Miami Breast Cancer Conference demonstrated that fam-trastuzumab deruxtecan-nxki (T-DXd) was associated with similar rates of treatment discontinuation in patients with HER2-low metastatic breast cancer compared with those observed in the phase 3 DESTINY-Breast04 (NCT03734029) trial.
Rates of discontinuation due to toxicity were 15% in the real-world cohort versus 16.2% in DESTINY-Breast04. Most discontinuations were attributed to interstitial lung disease (ILD)/pneumonitis. The incidence of ILD/pneumonitis was slightly lower in the real-world cohort at 10.0%, compared with 12.1% reported in the trial.
Treatment delays or holds were most commonly associated with ILD/pneumonitis, followed by nausea/vomiting and neutropenia, fatigue, diarrhea, anemia and reduced left ventricular ejection fraction, thrombocytopenia, respiratory infection, and rash. Dose reductions to manage toxicity most frequently involved neutropenia, followed by nausea/vomiting, fatigue, diarrhea and anemia, thrombocytopenia, ILD/pneumonitis, and blurred vision or respiratory infection.
Among patients who developed ILD/pneumonitis, 80.0% received corticosteroids. Additional management strategies included treatment discontinuation, treatment hold or delay, supportive care interventions, antibiotics, hospitalization, emergency department visits, unscheduled clinic visits, and dose reduction.
Baseline characteristics of the real-world cohort showed that 77.0% of patients had hormone receptor-positive disease, and 39.3% had at least one comorbidity. Disease stage distribution comprised 33.0% with stage II disease, 24.7% with stage IV, 19.7% with stage III, 12.3% with stage 0 to I, and 10.3% with unknown stage. Baseline performance status was not impaired in 72.0% of patients.
Patients had a median of two 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 setting, whereas 23.7% received it in the sixth line or later. Use by line of therapy was 23.3% in the third line, 20.3% in the fourth line, 15.7% in the second line, and 13.3% in the fifth line.
These findings reinforce the conclusion that the tolerability profile of T-DXd observed in clinical trials translates effectively into real-world practice. With manageable toxicity and low discontinuation rates, T-DXd remains a viable and scalable treatment option for patients with HER2-low metastatic breast cancer across diverse care settings.