7P Trastuzumab deruxtecan (T-DXd) for advanced breast cancer (ABC) patients (pts), regardless of HER2 status: A phase II study with biomarkers analysis (DAISY) - update analysis with longer follow-up

The HER2-targeted antibody-drug conjugate (ADC) T-DXd demonstrated efficacy in heavily pretreated HER2-over- and -low expressing ABC. We aimed to assess the activity of T-DXd in HER2-over/low expressing or IHC-0 ABC, to describe the drug mechanisms of action and to identify biomarkers associated to drug response or resistance. DAISY is an open-label phase II trial to assess the efficacy of T-DXd in ABC with extensive biomarkers analysis (1) in 3 cohorts: Cohort 1 (HER2 over-expressing: 3+ on IHC or ISH+), Cohort 2 (HER2 low-expressing: 1+ or 2+/ISH-) and cohort 3 (HER2-IHC 0). The primary endpoint was the confirmed objective response rate (ORR). Secondary endpoints were clinical benefit rate, duration of response (DOR), progression-free (PFS), overall survival (OS) and safety. Here we report clinical activity and safety with a longer follow-up of 38.4 months 95%CI: 35.3-40.9. 185 women and 1 man were enrolled between 2019 and 2021. Among the safety population (179 pts), median range age was 55 24-82 years, median number of previous metastatic line was 5 0-17 and 12 pts harbored triple-negative ABC. Median number of cycles was 10 1-63. In December 2023, 6 pts were still on-treatment. The table shows T-Dxd activity in the full analysis set population (177 pts). Important to note, PFS rate at 24 months was 31% 95%CI: 20-43 in cohort 1. A total of 173 pts (96.6%) had at least one treatment-related adverse event (TRAE). Eight pts (4.5%) had drug related ILD or pneumonitis (grade (G) 1 in 6 pts, G2 and G5 in 1 pt each), 18 pts discontinued treatment due to TRAEs.Table: 7PTotalCohort 1Cohort 2Cohort 3BOR confirmed n/N 95%CI86/177 (48.6%) 41.0; 56.248/68 (70.6%) 58.3; 81.027/72 (37.5%) 26.4; 49.711/37 (29.7%) 15.9; 47.0Median DOR (months) 95%CI8.5 6.8; 9.79.7 7.2; 17.97.6 4.4; 9.46.8 2.8; 17.5Median PFS (months) 95%CI7.1 6.6; 8.711.1 8.5; 14.46.8 4.6; 8.54.2 2.0; 5.7Median OS (months) 95%CI19.6 16.1; 22.331.2 22.4; Not Reached19.3 11.5; 22.112.1 8.3; 15.0 Open table in a new tab Consistent with previously reported data, T-DXd showed clinically meaningful activity in pts with HER2-overexpressing ABC and antitumour activity in those with HER2-low and non-expressing ABC during extended follow-up. Safety profile was consistent with previous reports. (1) Mosele F and alNat Med 2023