When do you consider HER2-targeting antibody drug conjugates in the first line setting for metastatic HER2 positive, ER negative breast cancer?  

This question cannot be answered for any specific situation with a high degree of reliability without a controlled clinical trial. In my opinion, there could be situations in which I would predict a favorable benefit/risk ratio to the use of T-DXd in first line as opposed to standard taxane + trastu...

Treating metastatic breast cancer is always a balance of efficacy and toxicity. The results with T-DXd are unprecedented in the 2nd and 3rd line and the degree of efficacy does raise the question of earlier use. From the DESTINY-Breast01 trial, in patients who had received prior T-DM1, the median PF...

In my opinion, the great activity observed with T-DXd in the DB03 study does not support the role of this drug in the first line setting in the general population. However, if the patient has received previous treatment with Trastuzumab-based therapy and we have a progression of the disease in the f...

TDM-1 may be a front line option in some patients who either refuse chemotherapy, are too frail, or have significant comorbidities. We know from MARIANNE that TDM-1 is at least as good as paclitaxel/trastuzumab, so not unreasonable in these situations, including in ER negative patients.

Drug-induced Interstitial Lung Disease (ILD) has been reported among patients with HER2-positive MBC receiving anti-HER2 therapies, including trastuzumab, lapatinib, T-DM1, T-DXd, and trastuzumab duocarmazine. The highest ILD incidence was reported in patients who received T-DXd (range 13.6–17...