485P Review of dosing and scheduling adjustments in patients receiving trastuzumab deruxtecan for metastatic breast cancer in a real-world setting

Methods: Data were collected from an Australian registry of patients with aTNBC who received SG from Oct 2021 -Sept 2024.Clinicopathologic characteristics, treatment patterns, adverse events and survival outcomes were examined.Results: Data on 143 patients from 19 sites were analysed (median follow up 29.8 months).Mean age was 55.1 years (24% 65 years).73% were ECOG 0-1.84% underwent germline testing (11% had a BRCA1/2 pathogenic variant).81% of patients had relapsed metastatic disease, with most common sites being nodal (66%), bone (52%) and lung (42%).18% had brain metastases at time of SG initiation.Median time from metastatic diagnosis to SG initiation was 15.0 months.62% of patients had received 2 prior lines of therapy for metastatic disease, most commonly capecitabine (25%), eribulin (18%) and carboplatin/gemcitabine (18%).22% had received immunotherapy in the metastatic setting prior to SG. 34% required SG dose reductions, due to toxicity from diarrhea (11%), fatigue (7%) and neutropenia (5%).27% received granulocyte-colony stimulating factor as primary prophylaxis (within 14 days of starting SG) and 12% as secondary prophylaxis.At time of analysis, 94% of patients discontinued SG due to progressive disease (73%), toxicity (8%) and death (4%).Median PFS and OS were 5.3 (95% CI 4.6-6.7)and 11.5 months (95% CI 8.5-14.4)respectively.Univariate analysis showed median OS of 16.0 and 10.0 months (HR 0.76, p = 0.10) for patients treated in 2L vs 3L and 13.9 vs 6.8 months (HR 0.55 p = 0.004) for those who relapsed >12 vs <12 months from date of their primary diagnosis.Conclusions: Analysis of real-world data for aTNBC patients treated with SG demonstrate survival outcomes consistent with the ASCENT clinical trial, with a manageable safety profile and no unexpected toxicities.Patients who relapsed within 12 months of their initial diagnosis had poorer outcomes, and there was a trend towards greater benefit when SG was used in an earlier line of therapy.