Dr LeVee on ADC Trials That May Inform the Evolution of Breast Cancer Management

Alexis LeVee, MD, chief Hematology & Medical Oncology fellow at City of Hope, discussed highly-anticipated readouts of clinical trials investigating antibody-drug conjugates (ADCs) in patients with HER2-positive metastatic breast cancer and triple-negative breast cancer (TNBC) that will be presented at the 2025 ASCO Annual Meeting.

One trial generating substantial interest is the phase 3 DESTINY-Breast09 trial (NCT04784715), which compared fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta) with the current standard first-line regimen of docetaxel, trastuzumab (Herceptin), and pertuzumab in HER2-positive metastatic breast cancer, LeVee began. A news release from April 2025 shared that treatment with T-DXd plus pertuzumab improved progression-free survival (PFS) compared with the standard of care; this benefit was observed across all prespecified patient subgroups. These findings may have important implications for the first-line treatment paradigm in this breast cancer subtype, she explained.

Similarly, the phase 3 ASCENT-04 trial (NCT05382286), which evaluated sacituzumab govitecan-hziy (Trodelvy) in combination with pembrolizumab (Keytruda) vs physician’s choice of chemotherapy plus pembrolizumab in patients with PD-L1–positive metastatic TNBC, reported improved PFS with the investigational combination in a separate April 2025 news release. The safety profile of the investigational combination was consistent with the known toxicities of each individual agent, supporting the potential clinical utility of this regimen, LeVee highlighted.

Several phase 2 studies of ADCs in breast cancer will be also presented at the meeting, LeVee stated. The phase 2 NeoSTAR trial (NCT04230109) evaluated neoadjuvant sacituzumab govitecan plus pembrolizumab in patients with early-stage TNBC. Additionally, the phase 2 OptiTROP-Breast05 study (NCT05445908) invetigated a novel ADC, sacituzumab tirumotecan (formerly SKB264/MK-2870), as a first-line treatment for patients with metastatic TNBC. Both studies may provide valuable insights into evolving treatment strategies for TNBC, LeVee concluded.