Lost HER.

We’ve known for a long time that continuing HER2-targeted therapy even after initial progression further improves outcomes in HER2(+) breast cancer. The T-ACT study was designed to assess the same hypothesis for advanced / metastatic HER2(+) gastric cancer. This phase 2 trial randomized 91 patients with trastuzumab-refractory disease to paclitaxel versus paclitaxel plus a continuance of trastuzumab. Unfortunately, median progression-free (3-4 months) and overall (10) survival as well as response rates (32-33%) were the same regardless of the additional trastuzumab. Interestingly, among 16 patients with available tissue upon progression with first-line trastuzumab, over two-thirds no longer expressed HER2. TBL: Once gastric cancer proves refractory to trastuzumab, it’s likely to remain that way. | Makiyama, J Clin Oncol 2020