KEY TAKEAWAYS
- The DESTINY-Breast04 phase III trial aimed to evaluate the durability of T-DXd’s clinical benefit in HER2-low mBC patients over extended F/U.
- The study analyzed OS and PFS.
- The results confirmed T-DXd’s lasting benefit in HER2-low mBC across HRs, with manageable safety even over longer use.
DESTINY-Breast04 tested a new drug called trastuzumab deruxtecan (T-DXd) against standard chemotherapy treatment of physician’s choice (TPC) in HER2-low metastatic breast cancer (mBC) patients (IHC 1+ or 2+/ISH-).
S. Modi and her research team spearheaded a study where they sought to investigate the lasting clinical advantages of T-DXd in HER2-low metastatic breast cancer (mBC) patients. They delved into prolonged follow-up data and released results from a pre-planned extended follow-up (F/U) conducted on March 1, 2023.
Their findings showcased T-DXd’s substantial extension of overall survival (OS) in both hormone receptor-positive (HR+) and hormone receptor-negative (HR-) patients when compared to standard treatment (23.4 months vs 16.8 months).
Patients were randomly allocated in a 2:1 ratio to receive either T-DXd or TPC. At the updated data cutoff (DCO), comprehensive analyses were undertaken for OS in both HR+ and the full analysis set (FAS). The progression-free survival (PFS), as evaluated by the investigator, was assessed in both HR+ and FAS. The investigation also included a thorough examination of safety parameters.
The median F/U duration was 32 months.T-DXd exhibited a median treatment duration of 8.2 months (range, 0.2-39.1 months), while the corresponding duration for TPC was 3.5 months (range, 0.3-19.7 months).
Grade ≥3 treatment-emergent adverse events (TEAEs) were less frequent in the T-DXd group compared to TPC (54.4% vs 67.4%). The most common TEAEs included gastrointestinal or hematological events; specifically, all-grade nausea was observed (T-DXd: 76.0%; TPC: 30.2%), vomiting (T-DXd: 40.7%; TPC: 13.4%) and decreased neutrophil count (T-DXd: 22.1%; TPC: 36.0%).
The exposure-adjusted incidence rates for any-grade TEAEs were 1.2 for T-DXd and 2.6 for TPC. No new adjudicated drug-related interstitial lung disease/pneumonitis events were reported with longer follow-up (primary DCO: 45 pts [12.1%] for T-DXd; 1 pt [0.6%] for TPC).
The study found a clinically meaningful improvement with T-DXd over TPC in HER2-low mBC, irrespective of HR status. It maintained a generally manageable safety profile with prolonged treatment duration. The research is funded by Daiichi Sankyo, Inc. and AstraZeneca.
Clinical Trial: https://clinicaltrials.gov/study/NCT03734029
Modi S, Jacot W, Iwata H, et al. ‘’Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Updated survival results of the randomized, phase III DESTINY-Breast04 study.’’ Annals of Oncology (2023) 34 (suppl_2): S334-S390. 10.1016/annonc/annonc1299.
