In patients with metastatic hormone receptor-positive, HER2-low breast cancer, how many and which lines of therapy would you recommend prior to using trastuzumab deruxtecan?

In spite of the exciting results observed with trastuzumab deruxtecan in DESTINY-Breast04, endocrine based therapy continues to be the most appropriate first line choice for the majority of patients with hormone receptor-positive, HER2-negative disease, particularly as we are now seeing median overa...

In patients with metastatic hormone receptor positive, HER2 low breast cancers, first line therapy is still CDK4/6 inhibitor plus endocrine therapy based on a meta-analysis which shows clinical benefit across all subgroups including bone only disease [1], which is not a specified subgroup in the DB4...

I would recommend T-DXd after CDK4/6 inhibitor and after 1 line of chemotherapy as in the DESTINY-Breast04 trial. Perhaps in visceral crisis, T-DXd could potentially be used before CDK4/6 inhibitor.

Updated answer - 12/04/2024

Recommended prior therapies include:

• First-line endocrine therapy with CDK4/6 inhibitors.
• Second-line endocrine therapy with targeted agents such as everolimus or alpelisib.
• Third-line chemotherapy, such as capecitabine or taxanes. T-DXd is typically used after at least tw...

For metastatic hormone receptor-positive, Her 2-low breast cancer, I would not use trastuzumab deruxtecan unless considered hormone refractory which would entail progression on CDK-4/6 i, AI, Fulvestrant. I would also favor using Capecitabine and PI3 Kinase inhibitors (when indicated) before conside...

Updated answer - 11/26/24

The FDA approval for trastuzumab deruxtecan (T-DXd) for HER2-low breast cancer requires prior chemotherapy in the metastatic setting or disease recurrence within 6 months of completing adjuvant chemotherapy. However, the recently published DESTINY-Breast06 study evaluated pa...

Endocrine therapy and Pik3 inhibitor then capecitabine then TDXd.

Would anybody consider T-DXd as first line in the rare patient with brain mets not amenable to surgery or radiation therapy due to location of the lesion?

The only time I would consider T-DXd prior to CDKi and endocrine therapy is visceral crisis or poor tolerance to CDKi in rare patients. If not, best use is after CDKi and one line of chemo.