T-DXd: Use Your Best Player First

In this CHM Conversations clip, Drs. Mouabbi and Tarantino explore how DESTINY-Breast06 is shifting the management for HER2-low metastatic breast cancer, not by offering a one-size-fits-all solution, but by giving oncologists real flexibility to tailor treatment to the biology in front of them. They opine that guidelines may be homogeneous, but the spectrum of breast cancer is anything but. For patients with rapid progression, visceral crises, or high disease burden where reaching the goalpost to the next line of therapy isn’t guaranteed, T-DXd has clearly outperformed standard chemotherapy and remains the strongest option to rescue control. However, for patients with indolent disease, oral options like capecitabine may remain viable — allowing oncologists to preserve T-DXd for later lines without compromising outcomes early on. Ultimately, DESTINY-Breast06 delivers the evidence needed to individualize: if a tumor demands immediate, aggressive pressure, T-DXd takes the lead; if the disease is slower-moving, de-escalation remains rational. Yet as Dr. Tarantino points out, the lack of mature overall survival data leaves room for debate — and some patients with initially indolent disease may still benefit from starting T-DXd earlier. This conversation captures a critical inflection point in HER2-low care, where clinical nuance, evolving survival data, and patient-centered strategy are redefining what optimal sequencing looks like.