Alpelisib and Fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the German PRAEGNANT trial.

Mutations in PIK3CA are one of several actionable mutations for patients with hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Alpelisib in combination with fulvestrant was the first approved PI3K inhibitor and was introduced in clinical practice in 2019. A lack of evidence for the use of alpelisib in the context of current treatment options like cyclin-dependent 4/6 inhibitor (CDK4/6i), highlights the importance of this analysis. We provide a real-world analysis of the use of alpelisib with the prospective German PRAEGNANT registry (NCT02338167). 57 patients with advanced breast cancer receiving alpelisib and fulvestrant were identified. 55 Patients had received prior CDK4/6i therapy. Progression-free survival (PFS) and overall survival (OS) were calculated for all patients, and stratified according CDK4/6i pre-treatment, using the Kaplan-Meier method. Subgroups (age, line of therapy, concomitant disease among others), somatic PIK3CA mutations, reasons for discontinuation and adverse events (AEs) were analyzed. The median PFS was 5.0 (95% confidence interval [CI], 3.1-9.4) months, and the median OS was 20.1 (95% CI, 14.6-30.8) months. Line of therapy and concomitant diseases appeared to affect PFS, while the line of therapy and preexisting diabetes influenced OS. However, subgroups were too small for statistical testing. Discontinuation was mainly due to tumor progression (56.1%). Hyperglycemia, rash and diarrhea were the most documented AEs. This prospective real-world analysis shows slightly shorter median PFS and OS times compared with the pivotal trials. Patients in our analyses received alpelisib in later therapy lines, which may explain the poorer outcome.