PIK3CA and Hyperglycemia: For clinical use of combination therapy, the toxicities of PI3K inhibition (rash, diarrhea, and hyperglycemia) may be potential challenges; however, a phase Ib study that included a cohort of PanNET patients treated with the PI3Kalpha inhibitor alpelisib and everolimus demonstrated that the combination could be given with dose reductions and that the sixteen-week progression-free survival rate was 35.3% in previously treated PanNET patients and 30.0% in a mixed cohort with prior mTOR inhibitor use [15].