5P Combination activity of T-DXd and dato-DXd with DNA damage response inhibitors

Background: In the KATHERINE trial, adjuvant trastuzumab emtansine (T-DM1) significantly improved invasive disease-free survival (IDFS) in patients with residual HER2-positive breast cancer following neoadjuvant therapy.Real-world data on T-DM1 biosimilars in the post-neoadjuvant setting remain limited, particularly in lowand middle-income countries.This study evaluated IDFS and safety outcomes of a T-DM1 biosimilar in routine Indian clinical practice.Methods: This retrospective, single-centre observational study included women with stage II-III HER2-positive breast cancer treated at Sunshine Global Hospital, Surat, India, between June 2021 and June 2025.All eligible patients received adjuvant trastuzumab emtansine biosimilar (Ujvira; 3.6 mg/kg administered intravenously every 21 days) following neoadjuvant chemotherapy and definitive surgery.IDFS was assessed using the Kaplan-Meier method, with subgroup comparisons performed using log-rank tests.Treatment-related adverse events were analysed descriptively.Results: Twenty-four patients were included (median age 60.3 years; 83.3% postmenopausal); 20.8% had stage II and 79.2% stage III disease.The median number of cycles was 11.Median IDFS was 14 months (95% CI: 13-15), with no deaths during follow-up.Invasive disease recurrence occurred in 20.8% of patients, most commonly involving bone, brain, and liver.Longer IDFS was observed in patients with stage III versus stage II disease (15 vs 13 months; p=0.045), mastectomy versus breastconserving surgery (15 vs 13 months; p=0.014), and 200 mg versus 160 mg dosing (14 vs 10 months; p=0.0004).Common adverse events included thrombocytopenia (95.8%), neutropenia (79.2%), and anaemia (41.7%), predominantly grade 1-2.Asymptomatic left ventricular ejection fraction reductions (<50%) occurred in 20.8% and were reversible. Conclusions:In this real-world post-neoadjuvant cohort, a trastuzumab emtansine biosimilar demonstrated encouraging short-term IDFS and a manageable safety profile, consistent with expectations from pivotal trial data and supporting its feasibility as a cost-effective adjuvant option in routine practice.