Efficacy and safety of alpelisib in patients with HR+HER2-negative metastatic breast cancer in real clinical practice: Results of a single-center observational retrospective study

Background. The combination of alpelisib with fulvestrant is the optimal targeted endocrine therapy for patients with hormone-positive (HR+) HER2-negative (HER2-) metastatic breast cancer (mBC) with mutations in the PIK3CA gene. This regimen has been shown to be highly effective in large phase II and III studies. However, randomized clinical trials cannot fully cover all possible clinical populations of pre-treated patients. Therefore, the real-world study of the efficacy and safety of the alpelisib + fulvestrant is warranted. Aim. A retrospective analysis of the real-world efficacy and safety of alpelisib in patients with pre-treated luminal HER2- mBC. Materials and methods. The study included 33 patients diagnosed with HR+ HER- mBC who received alpelisib in combination with fulvestrant in routine practice from 2020 to 2023. Twelve (36.4%) patients had a mutation in exon 9 of the PIK3CA gene, and 21 (63.6%) patients had a mutation in exon 20. Alpelisib was administered to pre-treated patients in different therapy lines: the median number of mBC treatment lines before alpelisib was 5 (1–8), 1 patient received alpelisib in line 1, 4 in line 2, 6 in line 3, 5 in line 4, 8 in line 5, 1 in line 6, 7 in line 7, and 1 in line 8. Patients with luminal B-type BC accounted for 72.7% (n=24). The ECOG status of 0, 1, and 2 points had 9.1%, 75.7%, and 15.2% of patients, respectively. Results. The median overall survival was 14.0±2.5 months (95% confidence interval 9–18.9), and the median progression-free survival was 6.0±2.7 months (95% confidence interval 0.7–11.3). The prognostic factor was an interruption of drug therapy for any reason, which increased the risk of mortality. The adverse event profile was consistent with data from previous randomized trials. Conclusion. The outcomes of therapy with alpelisib and fulvestrant show the effectiveness of this regimen in real-world settings in patients with HR+ HER2- advanced BC with a somatic mutation in the PIK3CA gene.