LBA2 Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in pretreated, inoperable/metastatic HR+/HER2– breast cancer (BC): Additional safety analysis from TROPION-Breast01

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In TROPION-Breast01 (NCT05104866), the antibody-drug conjugate Dato-DXd showed improved efficacy and was well tolerated compared with investigator's choice of CT (ICC) in patients (pts) with HR+/HER2– BC. Here we report additional safety analyses. Study design was previously described; safety was a secondary endpoint. Mouthwash use was advised (steroid mouthwash strongly recommended if available), and ophthalmologic assessment was required per regulatory request at screening and every three 21-day cycles. At data cutoff (Jul 2023), 360 pts received Dato-DXd, 351 ICC. Median treatment duration was longer with Dato-DXd vs ICC (6.7 vs 4.1 mo). Rate of ≥G3 treatment-related adverse events (TRAEs) was lower with Dato-DXd vs ICC (21% vs 45%). TRAEs of special interest (AESIs) with Dato-DXd included stomatitis/oral mucositis (OM) (56%), ocular events (OE; 40%), and adjudicated drug-related interstitial lung disease (ILD; 3%). OE were identified mainly via mandatory eye exams; >50% were dry eye. Stomatitis/OM and OE were mostly low grade (asymptomatic/mild, G1 in 25% and 32% of all Dato-DXd pts, respectively); both were well managed by toxicity management guidelines (TMGs), with low rates of dose interruption (1% and 3%) and discontinuation (both 0.3%). In contrast, the ICC safety profile was most notable for high-grade neutropenia (≥G3 in 31% of ICC pts) leading to dose interruption (17%)/reduction (13%). Adjudicated drug-related ILD with Dato-DXd was mostly low grade (asymptomatic, G1 in 1% of Dato-DXd pts). AESIs generally occurred in the first few cycles: median onset of stomatitis/OM at Cycle 2, OE at Cycle 3, ILD at Cycle 4. Median time to resolution was 37, 67, 28 days for stomatitis/OM, OE, ILD. Further data from TROPION-Breast01 showed that AESIs with Dato-DXd were typically low grade, occurred in the first few cycles and were manageable using TMGs. Moreover, with Dato-DXd the rate of ≥G3 TRAEs was less than half that with ICC and fewer TRAEs led to dose interruption/reduction, showing that Dato-DXd offers better tolerability vs ICC and further emphasizing the potential for Dato-DXd as a favourable treatment option in clinical practice.