Dr LeVee on Selecting and Sequencing ADCs in Breast Cancer

"[Sequencing] is a tough question; we really have to look to see what the trial how the trial investigated the drug in terms of the patient population and the outcomes [to inform our choices]."

Alexis LeVee, MD, chief Hematology & Medical Oncology fellow at City of Hope, discussed the complex process of selecting and sequencing available antibody-drug conjugates (ADCs) for patients with breast cancer. According to Levee, clinical decisions must be supported by clinical trial data, specifically examining the patient population studied and the documented outcomes. Clinical practice often requires that the drug be utilized exactly as it was investigated in the trial; for example, if a drug was evaluated after one or two prior lines of chemotherapy, it must be used in that sequence clinically.

Levee highlighted the importance of sample size and trial design using the phase 3 DESTINY-Breast06 trial (NCT04494425) as an example. This trial compared treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) against physician’s choice of either capecitabine [Xeloda] or a taxane such as nab-paclitaxel [Abraxane] or paclitaxel, in patients with hormone receptor–positive, HER2-low or HER2-ultralow metastatic breast cancer in the second- or later-line setting.

A critical limitation pointed out by Levee concerned the size of the HER2-ultralow patient population within that trial. Because this subgroup was quite small, there is insufficient data to support how T-DXd should be used extensively, such as in the triple-negative breast cancer setting. Ultimately, Levee asserted that decisions regarding ADC utilization should be strictly based on the sample sizes and the precise manner in which the drug was studied during the trial.