Numerous studies have evaluated the role of PI3K inhibitors in breast cancer, some with positive results but an excess toxicity profile. The SOLAR-1 trial is the first to show a clinically meaningful benefit (PFS nearly doubled) with the addition of alpelisib in patients who harbor a PIK3CA mutation. Although very few patients on this study (6%) had received prior CDK4/6 inhibition, the benefit was similar in this population; therefore, this represents a reasonable option for patients with tumors harboring a PIK3CA mutation post-progression on a CDK4/6 inhibitor.
PIK3CA mutations occur in approximately 40% of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. The PI3Kα-specific inhibitor alpelisib has shown antitumor activity in early studies.
Treatment with alpelisib-fulvestrant prolonged progression-free survival among patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer who had received endocrine therapy previously.
