HER2+ BC: A Year in Review and Updates from SABCS - Episode 2

HER2+ BC: Unanswered Questions in Sequencing

Andrew Seidman, MD, provides insight on clinical sequencing for patients with advanced HER2-positive breast cancer.

Hatem Soliman, MD: For the most part, we are looking at pertuzumab, trastuzumab, and a taxane as a first-line treatment. T-DM1 [trastuzumab emtansine] is still the second line go-to, and then the third-line setting, we have trastuzumab deruxtecan, we have tucatinib with capecitabine, and trastuzumab. That third-line setting is where some people are asking, what are those clinical determinates that we may use to help us pick?

Andrew Seidman, MD: This is a data-free zone there. There is not a randomized study yet, to guide what to do for the patient who has progressed despite CLEOPATRA therapy in the first line, and then EMILIA therapy, or T-DM1 [trastuzumab emtansine], in the second line. The obvious suspects now are trastuzumab deruxtecan, another antibody-drug conjugate, or switching to the HER2CLIMB regimen of capecitabine, tucatinib, and trastuzumab. There is not an obvious answer. There is more known about the potential benefits of tucatinib and capecitabine in patients with pre-existing CNS [central nervous system] disease. This is an area of my own interest and research, and I have done some correlative work and some clinical work with lapatinib dosing and scheduling in HER2-positive brain metastasis. There is not enough known about trastuzumab deruxtecan’s potential role in the CNS to dismiss it as still a potentially relevant third-line agent. The algorithm does follow CLEOPATRA, EMILIA, and then dealer’s choice between HER2CLIMB and DESTINY-Breast01 therapy.

Transcript edited for clarity.