With advancing and new therapies emerging for metastatic HER2+ breast cancer, how does one decide between options for third line therapy at time of progression?  

Barring any contraindications, tucatinib would be my preferred third line after progression on traz/pertuz and ado-traz. 

Margetuximab plus eribulin or gemcitabine or vinorelbine, Fam-trastuzumab deruxtecan, neratinib+capeciatbine lapatinib trastuzumab combinations are all Category 2A NCCN recommendations in this setting as well as tucatinib+capeciatbine+trastuzumab.