Baseline Serum Albumin Is Associated With Severe Adverse Events During Trastuzumab Deruxtecan Treatment in Metastatic Breast Cancer

Background/Aim: Trastuzumab deruxtecan (T-DXd) is associated with a high incidence of severe adverse events (AEs); however, clinically useful baseline predictors of severe AEs are limited. This study aimed to explore factors associated with severe AEs in patients with metastatic breast cancer receiving T-DXd using least absolute shrinkage and selection operator (LASSO) regression. Patients and Methods: This single-center retrospective study included 31 patients with HER2-positive or HER2-low metastatic breast cancer who received T-DXd. Severe AEs were defined as grade ≥3 AEs. LASSO logistic regression was used to select candidate factors from 21 clinical and laboratory variables. Variables selected at λ1se were entered into multivariable logistic regression, and the optimal cutoff value was estimated using receiver operating characteristic (ROC) curve analysis. Results: Severe AEs occurred in 11 patients (35.5%). LASSO regression selected serum albumin and hemoglobin as candidate variables. In multivariable analysis, serum albumin was independently associated with severe AEs [odds ratio (OR)=0.065; 95% confidence interval (CI)=0.006-0.717; p<0.05], whereas hemoglobin was not statistically significant (p=0.07). ROC analysis identified a cutoff of 3.5 g/dl (area under the curve, 0.85; 95%CI=0.71-1.00; sensitivity, 91%; specificity, 75%). Severe AEs occurred more frequently in patients with serum albumin ≤3.5 g/dl than in those with serum albumin >3.5 g/dl (66.7% vs. 6.2%; p<0.05). Conclusion: Lower baseline serum albumin may help identify patients at increased risk of severe AEs during T-DXd treatment for metastatic breast cancer.