Options in Breast Cancer After HER2+ Targeted Therapy

Mark Pegram, MD: Next, let’s talk about what options there are for patients even after, let’s say, a dual-antibody combination and T-DM1 [trastuzumab emtansine]. What will be the traditional options prior to the recent FDA approvals? What kinds of outcomes would you have expected until recently?

Julie R. Gralow, MD: Well, lapatinib with capecitabine received approval, although over time it’s been pushed back. Virtually all the recently approved drugs have proven to be better than lapatinib with capecitabine with or without trastuzumab. We also frequently reuse trastuzumab in combination with other chemotherapy agents and have shown if a patient has already had a taxane with HER2 [human epidermal growth factor receptor 2] antibodies, that you can go third, fourth line with other chemotherapy agents that are proven to be safe and have synergy with trastuzumab. That was also commonly maybe a third-line approach after the combined TRASTUZ-PERTUZ [trastuzumab, pertuzumab] first line and then T-DM1 [trastuzumab emtansine]. Now we’ve got several new agents with efficacy and we don’t know which to use in what order. Are we going to move them up earlier?

There was an interesting abstract submitted to ASCO [American Society of Clinical Oncology] 2020 Annual Meeting, that came out of the Japanese group. It just looked, at after patients’ had progressed on T-DM1 [trastuzumab emtansine], what was being used in the real world. At that time, it was before the metastatic neratinib approval, tucatinib, or the trastuzumab deruxtecan approval. And it was a mishmash of everything: switching out the chemotherapy with trastuzumab, continuing pertuzumab sometimes beyond as well, adding lapatinib and capecitabine. But that’s already out of date. We’ve got a whole bunch of other active agents that are much more exciting than those choices. We’re starting to prescribe them and need more help in terms of knowing which tumors and which patients should get which of these drugs—that are very efficacious—in what order.

Transcript edited for clarity.