Would you use T-DXd as a first-line agent for a patient who developed early metastatic relapse of HER2+ urothelial cancer shortly after standard perioperative chemo/immunotherapy, over other standard non-targeted treatments?

Currently, for first-line therapy in the metastatic setting, I would recommend enfortumab vedotin in combination with pembrolizumab, with T-DXd as a potential next-line option for patients with HER2 3+ IHC. However, there is still a need to see if HER2-targeted ADCs have a role in first-line.

In HER2+ urothelial cancer progressing quickly after platinum and checkpoint inhibition, or after enfortumab vedotin plus immunotherapy, T-DXd is a strong treatment option. In DESTINY-PanTumor-02, HER2 3+ patients had a 56% response rate. We obtain baseline echocardiograms and PFTs for those with a ...

EV-302, which led to the approval of EV+ pembrolizumab, excluded patients with prior IO exposure. This is especially important when there is “early” progression after IO, like in this case. The more data-driven options are EV alone vs Enhertu. Data (from 2 different studies) shows ORR of 40.6% with ...