A real-world single-center cohort study on the tolerability of trastuzumab deruxtecan for HER2+ metastatic breast cancer

Introduction: The DESTINY-B01 trial led to trastuzumab deruxtecan (T-DXd) approval for human epidermal growth factor receptor-2 (HER2+) metastatic breast cancers (mBCs), with efficacy further confirmed by DESTINY-B03, demonstrating improved progression-free and overall survival versus trastuzumab emtansine. Despite its efficacy, T-DXd had notable adverse events (AEs), including interstitial lung disease, necessitating real-world studies on safety and tolerability. Findings from such studies may help guide treatment selection and inform risk-benefit discussion in routine clinical practice. Methods: A real-world cohort study evaluated the safety and tolerability of T-DXd in patients with HER2+ mBC. De-identified patient data, tumor characteristics, AEs, dose modifications, and discontinuation rates due to AEs were analyzed. Results: Between January 2020 and June 2024, 85 predominantly non-Hispanic white patients with a median age of 57 years were treated. Notably, 17.6% had an ECOG performance status of 2-3, 69.4% had 1-2 prior metastatic treatments, 94% had visceral involvement, and most received primary prophylaxis with dexamethasone and palonosetron. Approximately 29.4% initiated treatment at a reduced dose; 40% required further dose reductions, primarily due to fatigue (9.4%). Permanent discontinuation due to AEs occurred in 10.6%. Common AEs included fatigue (95.3%), alopecia (14.1%), and peripheral neuropathy (14.1%). Grade ≥3 AEs were infrequent and included neutropenia (10.6%), elevated aspartate aminotransferase (2.4%), elevated alkaline phosphatase (2.4%), and interstitial lung disease (1.2%). No grade 5 events were observed. Conclusion: T-DXd demonstrated acceptable tolerability with manageable AEs in real-world patients with HER2+ mBC, aligning with clinical trial outcomes and supporting its continued use in clinical practice.