Would you risk offering alpelisib or everolimus to a patient with metastatic ER+ HER2- breast CA with Type 1 DM?

In the randomized phase 3 study with alpelisib (Andre, 2019 NEJM) patient with type 1 diabetes or uncontrolled type 2 diabetes were excluded. Nonetheless, the most frequent adverse events of grade 3 or 4 were hyperglycemia (36.6% in the alpelisib–fulvestrant group). Given lack of data and high incidence of hyperglycemia, I would be concerned about the use of alpelisib in a patient with type 1 DM although depending on their glycemic control and comfort of their endocrinologist and shared decision making with patient, it may be considered with very careful monitoring.  In the phase 3 study with everolimus (Baselga, 2012 NEJM), hyperglycemia rates were lower (4%) and this option is perhaps a more prudent choice in this clinical scenario.