When would you consider fulvestrant + alpelisib in a postmenopausal patient who has HR+, PIK3CA mutant, metastatic breast cancer instead of initial CDK4/6 inhibitor therapy?

Given that SOLAR-1 study enrolled patients who previously progressed after at least 1 line of endocrine therapy for metastatic disease, I would not offer alpelisib as front line therapy. My preference for front line therapy for metastatic, HR+, PIK3CA mutation-positive breast cancer is a combination of an endocrine agent with CDK4/6 inhibitor given level 1 evidence from large randomized clinical trials showing overall survival benefit when CDK4/6 inhibitors were added to endocrine therapy backbo...