Alpelisib Efficacy in Hormone Receptor-Positive HER2-Negative PIK3CA-Mutant Advanced Breast Cancer Post-Everolimus Treatment.

This real-world cohort analysis assessed the efficacy of alpelisib and endocrine treatment (ET) combinations in a post-everolimus setting. Thirteen women who started alpelisib and ET at standard doses between 2018 and 2022 for advanced breast cancer (ABC), after undergoing CDK4/6i and everolimus treatment, were eligible for the study entry. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR) and clinical benefit rate (CBR), with different molecular profiling. The patients had previously received a median of four (range 3-8) systemic treatments, including CDK4/6i and everolimus. The median PFS on alpelisib was 5.5 months (range 0.5-10), and four women each had an ORR and three (23%) had a stable disease. The 6-month CBR was 46.1%, similar to the BYLeive study cohort C (47.8%). Notably, our cohort included patients with a long CBR under everolimus treatment (median 6 months, range 1-18); however, the responses to alpelisib and everolimus were not correlated (Pearson r = -0.23, <i>p</i> = 0.44). The <i>PIK3CA</i>, <i>P53</i>, <i>ARID</i>, <i>GATA3</i>, and <i>ESR1</i> mutations were not associated with the 6-month CBR. Despite heavy pre-treatments, including everolimus, alpelisib was clinically relevant in our cohort, even among patients with an <i>ESR1</i> mutation. The best treatment sequence for PIK3CA/mTOR inhibitors warrants examination in future trials on PIK3CA-mutant inpatients with luminal ABC.