In a patient with HER2+ breast cancer who develops metastatic recurrence after receiving neoadjuvant or adjuvant T-DXd, what will then be your approach to first-line metastatic therapy?

I would not employ first-line T-DXd in patients who had received 10 or more doses as adjuvant therapy and recurred, and would not consider a rechallenge until later lines of therapy. If patients had only received 4 doses as neoadjuvant therapy and recurred more than 2-3 years after completing therap...

There is currently no prospective data to support using T-DXd as first-line treatment in the metastatic setting in patients who have already received it in the (neo) adjuvant setting. Prior ADC exposure is known to reduce the efficacy of subsequent ADC treatment, which can be an issue if the disease...

This is a newly created clinical scenario. T-DXd was only approved in the (neo)adjuvant setting in May 2026 (neoadjuvant with THP per DESTINY-Breast11, and post-neoadjuvant for residual disease per DESTINY-Breast05). The approach should be individualized.

I would first confirm biology at recurrence b...

Patients in the CLEOPATRA trial (1L THP in mHER2+ BC) were allowed to have received prior anti-HER2 targeted therapy in the (neo) adjuvant setting if they had not recurred within 12 months. About 29% of patients in DB09 had (neo) adjuvant anti-HER2 targeted therapy. Extrapolating from this, I think ...