Abstract
ABSTRACT
Background:
Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate with substantial activity in previously treated HER2-positive metastatic breast cancer. However, treatment-related toxicities, particularly hematological adverse events and interstitial lung disease (ILD)/pneumonitis, may require treatment interruption, dose reduction, or permanent discontinuation.
Objective:
To evaluate safety profile, treatment modifications, associated with T-DXd in patients with HER2 positive metastatic breast cancer.
Patients and Methods:
A study of 26 patients with T-DXd treatment was analyzed. Baseline characteristics, prior HER2-directed therapies, treatment exposure, adverse events, dose interruptions, dose reductions, and treatment discontinuation were evaluated. Categorical variables were summarized as frequencies and percentages, while continuous variables were summarized using median and interquartile range. Fisher’s exact test was used for exploratory associations.
Results:
The median age was 49 years, and all patients had previously received trastuzumab and T-DM1. The objective response rate was 61.5%, while the disease control rate was 96.2%. Grade ≥3 treatment-related adverse events occurred in 30.8% of patients. Neutropenia was the most frequent severe toxicity, occurring in 23.1%. Treatment interruption occurred in 34.6%, dose reduction in 23.1%, and permanent discontinuation due to adverse events in 15.4%. Grade ≥3 adverse events were significantly associated with dose reduction (62.5% vs 5.6%; p = 0.0045). ILD/pneumonitis occurred in 11.5% of patients; all cases were Grade 2 and resulted in permanent discontinuation. ILD/pneumonitis was significantly associated with adverse-event-related discontinuation (100% vs 4.3%; p = 0.0015). Disease progression was the leading cause of treatment discontinuation.
Conclusion:
T-DXd demonstrated substantial clinical activity in heavily pretreated HER2-positive metastatic breast cancer, but clinically significant toxicity frequently affected treatment delivery. Neutropenia was the predominant severe toxicity, whereas ILD/pneumonitis was the most important treatment-limiting adverse event. Proactive toxicity monitoring, early recognition of ILD/pneumonitis, appropriate supportive care, structured dose modification, and multidisciplinary clinical-pharmacy involvement are essential to optimize treatment safety and continuity.
Keywords: Trastuzumab deruxtecan(T-DXd); HER2 positive metastatic breast cancer; interstitial lung disease; dose modification; treatment discontinuation; clinical pharmacy.
| Has the manuscript been published | not published |
|---|---|
| Intend to be published in the IJPS ? | NO |
