Résumé
LBA1000
Background: T-DXd is approved for HER2-low (IHC 1+ or 2+/ISH-negative) mBC after ≥1 line of chemotherapy (CT). DB-06 (NCT04494425) evaluated T-DXd in pts with HER2-low or -ultralow (IHC 0 with membrane staining), HR+ mBC after disease progression (PD) on endocrine-based therapy and no prior CT for mBC. Methods: Pts with HER2-low or -ultralow, HR+ mBC were randomized 1:1 to T-DXd 5.4 mg/kg or TPC. Pts had no prior CT for mBC, with ≥2 lines of ET for mBC, or 1 line of ET for mBC if PD occurred ≤24 months (mo) of adjuvant ET or ≤6 mo of ET+CDK4/6i for mBC. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in HER2-low. Key secondary endpoints were PFS in intent-to-treat (ITT = HER2-low and -ultralow) and overall survival (OS). Other endpoints included objective response rate (ORR) and safety. Results: As of Mar 18, 2024, 866 pts (HER2-low, n=713; HER2-ultralow, n=153) were randomized; 90.4% had prior CDK4/6i. TPC group pts were selected for capecitabine (59.8%), nab-paclitaxel (24.4%) or paclitaxel (15.8%). T-DXd significantly improved PFS vs TPC in HER2-low (HR, 0.62 [95% CI 0.51, 0.74], P<0.0001; median, 13.2 vs 8.1 mo). ITT and HER2-ultralow results were consistent with HER2-low (Table). Median treatment duration was 11.0 mo (T-DXd) vs 5.6 mo (TPC). OS was immature at first interim analysis (HER2-low HR, 0.83 [95% CI 0.66, 1.05], P=0.1181; median follow up, 18.6 mo). Grade (Gr) ≥3 drug-related adverse events occurred in 40.6% (T-DXd) vs 31.4% (TPC). Adjudicated interstitial lung disease / pneumonitis occurred in 49 (11.3%; 0.7% Gr 3/4, 0.7% Gr 5) vs 1 (0.2% Gr 2) pts receiving T-DXd vs TPC. Conclusions: T-DXd showed a statistically significant and clinically meaningful PFS benefit vs TPC (CT) in HER2-low mBC. HER2-ultralow results were consistent with HER2-low. Safety was in line with known profiles. DB-06 establishes T-DXd as a standard of care following ≥1 endocrine-based therapy for pts with HER2-low and -ultralow, HR+ mBC. Clinical trial information: NCT04494425 .[Table: see text]