4CPS-125 Effectiveness and safety of trastuzumab deruxtecan for the treatment of unresectable or metastatic HER2-positive breast cancer

<h3>Background and Importance</h3> Trastuzumab deruxtecan has shown promising efficacy results in clinical trials for unresectable or metastatic HER2-positive breast cancer. It is crucial to assess whether these outcomes are replicated in real-world studies. <h3>Aim and Objectives</h3> To evaluate the effectiveness and safety of trastuzumab deruxtecan in patients with unresectable or metastatic HER2-positive breast cancer in a tertiary hospital. <h3>Material and Methods</h3> Retrospective observational study that included all women who received trastuzumab deruxtecan until September-2024. Data collected included demographics (age), cancer staging, oestrogen and progesterone receptor status (positive or negative), metastatic or non-metastatic debut of breast cancer, metastases at baseline, performance status, treatment line which trastuzumab deruxtecan is used in, number of cycles and treatment reductions/delays. Effectiveness was assessed by overall survival (OS) and progression-free survival (PFS), while safety was assessed by recording adverse events (AEs). The Kaplan-Meier method and SPSS-software (V25.0) were used for survival analyses. <h3>Results</h3> 33 patients were included, median age 54 years (range 37–80). All patients were stage IV, 72.7% and 48.5% were oestrogen and progesterone receptor-positive respectively and 48.5% had metastatic cancer at diagnosis. Before trastuzumab deruxtecan, 57.6% of patients had bone metastases, 48.5% had liver, 27.3% brain, 24.2% lung, 21.2% lymph node, 6.1% skin, and 3% had ovarian, pleural, and pericardial metastases. 48.5% had ECOG-0, 48.5% ECOG-1 and 3% ECOG-2. Trastuzumab deruxtecan was used first-line in 3% of patients, second-line in 42.5% of patients and third-line or higher in 54.5% of patients. The median number of cycles received was 17 (range 3–35). 48.5% and 60.6% of patients required at least one dose reduction or treatment delay due to drug toxicity respectively. Median OS was not reached while median PFS was 18.9 months (95% CI, 13.6-NR). Adverse events occurred in 93.9% patients, with the most common being nausea (87.1%), asthenia (67.7%), anaemia (38.7%), vomiting (32.3%), diarrhoea and neutropenia (25.8%), skin rash and headache (22.6%), hyporexia and neurotoxicity (19.4%), hepatotoxicity, abdominal pain, and thrombopenia (12.9%), dysgeusia (9.7%), constipation, mucositis, pneumonitis (6.5%), and heart failure (3.2%). <h3>Conclusion and Relevance</h3> Trastuzumab deruxtecan is effective, with a 18.9-month PFS median, but it is associated with a high rate of adverse events, necessitating close clinical monitoring. Pharmacists play a key role in managing toxicities and adjusting treatment to optimise patient outcomes. <h3>References and/or Acknowledgements</h3> No conflict of interest. <h3>Conflict of Interest</h3> No conflict of interest