In patients with newly diagnosed HER2+ early breast cancer who may be eligible for both neoadjuvant or adjuvant T-DXd, what will be your standard sequencing?

Trastuzumab deruxtecan (T-DXd) is currently recommended in the adjuvant setting for patients with residual invasive disease after neoadjuvant therapy, based on the DESTINY-Breast05 trial, while its use in the neoadjuvant setting remains investigational.

Ongoing neoadjuvant trials are evaluating T-DXd...

I think most patients who are high risk as defined by DB-11 and relatively fit would get TDXd neoadjuvant for 4 cycles in the hope of de-escalating the adjuvant therapy with a pCR. I do want to point out that 30% of the patients didn’t finish all of DB-05 adjuvant therapy. Their outcomes weren’t br...

I lean toward giving eligible patients neoadjuvant T-DXd when possible. This is mainly due to the increased incidence of interstitial lung disease seen in DESTINY-Breast05, likely due to the longer treatment course. My hope is that 4 cycles of T-DXd given in the neoadjuvant setting could spare patie...

My approach since ASCO 2025, following reporting of the CompassHER2-pCR and neoCARHP trials, has been to employ initial THP and then assess for a complete/near complete imaging response, including no residual enhancement on breast MRI. If present, would proceed with surgery and employ T-DM1 if resid...