TH3RESA - Phase 3 Study of T-DM1 vs. Treatment of Physician’s Choice in HER2-Positive Metastatic Breast Cancer (MBC) — Primary Results
Background: T-DM1, an antibody-drug conjugate comprising the cytotoxic agent DM1 linked to trastuzumab, and is approved in several countries for patients (pts) with MBC previously treated with trastuzumab and a taxane. TH3RESA is a phase 3 study evaluating T-DM1 vs. treatment of physician’s choice (TPC) in pts with progressive disease (PD) after ≥ 2 HER2-directed regimens for MBC.
Methods: Pts with centrally confirmed HER2-positive unresectable locally advanced BC or MBC with PD after ≥ 2 HER2-directed regimens, including trastuzumab and lapatinib, in the unresectable recurrent/metastatic setting and a taxane (any setting) were randomized 2:1 to T-DM1 (3.6 mg/kg IV q3w) or TPC. Co-primary endpoints were progression-free survival (PFS) by investigator and overall survival (OS). After EMILIA data were reported, crossover from TPC to T-DM1 was allowed post-progression.
Results: At the 11 Feb 2013 cutoff, 602 pts were randomized; 44 pts in the TPC arm had crossed over to T-DM1. TPC comprised HER2-directed regimens (83.2%) and single-agent chemotherapy (16.8%). Pts had received a median of four prior regimens (excluding hormonal therapy) in the recurrent/metastatic setting, and the majority (75.1%) had visceral disease.
PFS and objective response rate (ORR) were significantly improved with T-DM1; the interim OS analysis showed a similar trend, but the stopping boundary was not crossed (Table). PFS benefit was consistent across subgroups, including age, visceral involvement, number of prior regimens, and TPC type.
The T-DM1 safety profile was consistent with prior studies. Fewer grade ≥3 adverse events (AEs) overall were reported for T-DM1 vs TPC (32.3% vs 43.5%). More grade ≥3 thrombocytopenia (4.7% vs 1.6%) was reported with T-DM1. More grade ≥3 neutropenia (2.5% vs 15.8%), febrile neutropenia (0.2% vs 3.8%), and diarrhea (0.7% vs 4.3%) were reported with TPC.