LBA11 Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Primary results from the randomised phase III TROPION-Breast01 trial

The TROP2-directed antibody-drug conjugate Dato-DXd demonstrated promising activity in heavily pre-treated patients (pts) with inoperable or metastatic HR+/HER2-BC in the Phase 1 TROPION-PanTumor01 trial (NCT03401385). Here we report primary PFS results from the global, Phase 3 TROPION-Breast01 trial (NCT05104866). Adult pts with inoperable or metastatic HR+/HER2-BC, who had experienced progression on endocrine therapy (ET) and for whom ET was unsuitable, and who had received 1-2 prior lines of systemic chemotherapy (CT), were randomised 1:1 to Dato-DXd (6 mg/kg Q3W) or investigator’s choice of CT (ICC; eribulin, vinorelbine, capecitabine, or gemcitabine) until progression or unacceptable toxicity. Dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1, and overall survival (OS). 732 pts were randomised (Dato-DXd: 365; ICC: 367). Median age (range) was 56 (29–86)/54 (28–86) yrs in the Dato-DXd/ICC groups. At data cut-off (17 Jul 2023), 93/39 pts in the Dato-DXd/ICC groups were ongoing treatment. Results are shown in the table. Pts receiving Dato-DXd had significantly improved PFS vs ICC (HR 0.63 [95% CI 0.52–0.76]; p<0.0001). OS data were not mature; a trend for improvement favouring Dato-DXd was observed. Pts receiving Dato-DXd had lower rates of grade ≥3 TRAEs and dose reductions vs ICC (Table). TROPION-Breast01 met the primary endpoint of PFS; the study continues to final OS. Pts receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS compared with ICC, along with a favourable and manageable safety profile. Results support Dato-DXd as a novel treatment option for pts with inoperable or metastatic HR+/HER2-BC who have received 1–2 prior lines of CT.Table: LBA11Dato-DXdICCEfficacyN=365N=367PFSMedian PFS (BICR), mo (95% CI)6.9 (5.7‒7.4)4.9 (4.2‒5.5) HR (95% CI)0.63 (0.52‒0.76); p<0.0001Median PFS (investigator assessed), mo (95% CI)6.9 (5.9‒7.1)4.5 (4.2‒5.5) HR (95% CI)0.64 (0.53‒0.76)PFS rate (BICR), % (95% CI)6 mo 9 mo53.3 (47.7‒58.5)37.5 (31.9‒43.2)38.5 (32.8‒44.1)18.7 (13.8‒24.3)OS* HR (95% CI)0.84 (0.62‒1.14)ResponseConfirmed ORR (BICR), % (n)36.4 (133)22.9 (84)SafetyN=360N=351TRAEs, %Any grade Grade ≥393.620.886.344.7AEs associated with dose reduction/discontinuation, %23.1/3.132.2/2.8∗23% maturity.AEs, adverse events; mo, months; ORR, objective response rate; TRAEs, AEs possibly related to study treatment. Open table in a new tab