How do you decide on 2nd line therapy in a patient with HER2+ metastatic esophageal/gastric cancer who progresses after initial response to trastuzumab-based chemotherapy?  

After progression on trastuzumab-based front-line therapy, there is at least a 30% chance that the patient will lose HER2 expression. Thus, if I am considering further HER2-directed therapy, I will typically confirm continued HER2 expression. Based on the T-ACT trial, a randomized trial evaluating c...

In general, for patients with metastatic HER2+ gastroesophageal cancer who progress following front-line therapy consisting of chemotherapy + trastuzumab (for example, our institutional preference is FOLFOX/trastuzumab in the first-line setting), I will commonly switch chemotherapy backbones, for ex...

It's our practice to try to biopsy a lesion that's progressing on 1st-line trastuzumab based therapy to confirm that the tumor remains Her2 positive. Assuming that it is, the textbook answer is that there is currently equipoise between ramucirumab/paclitaxel vs. T-DXd as this is the question of the ...

The DESTINY-Gastric02 study showed a significant benefit of T-Dxd in the second-line setting. It is certainly an appealing choice over paclitaxel + ramucirumab for patients who initially responded to trastuzumab + chemotherapy ± pembrolizumab in first-line, particularly for patients who have ...

I tend to recheck HER2 testing at the time of progression - either by tissue or a liquid assay. If HER2 positivity remains, then I would probably select T-Dxd as the second line therapy and reserve ram/paclitaxel as 3rd line. While the efficacy of ramucirumab +/- paclitaxel vs T-Dxd is not yet deter...