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Abstract
Introduction. The majority of patients (70%) with HR+/Her2-negative metastatic breast cancer (mBC) experience disease progression due to changes in the regulation of the PI3K-Akt-mTOR signalling cascade. One frequent cause of this process is mutations in the PIK3CA gene encoding phosphatidylinositol-3-kinase (PI3K).
Aim. To evaluate the efficacy and tolerability of alpelisib in combination with fulvestrant in patients with HR+/Her2-negative mBC.
Materials and methods. A retrospective single-center study was conducted at the National Medical Research Radiological Centre of the Russian Ministry of Health in 2023–2024. All patients had a confirmed PIK3CA gene mutation. The efficacy of alpelisib was assessed by analyzing median progression-free survival (mPFS), calculated from the initiation of treatment until radiological progression (per RECIST 1.1 criteria) and/or discontinuation due to unacceptable toxicity. The PFS was evaluated using the Kaplan–Meier method.
Results. The study included 35 patients with HR+ Her2/neu-negative mBC. The median age was 53 years. Most patients (n = 23, 65.7 %) were initially diagnosed with with stage I–III breast cancer, and 88.6 % (n = 31) received alpelisib as part of the 2nd, 3rd, or later-line of therapy. ECOG performance status at baseline was 0 in over half of the participants (54 %). Invasive carcinoma of no special type (NST) was diagnosed in 30 patients (85.7 %), lobular carcinoma in 4 (11.4 %), and mucinous carcinoma in 1 (2.9 %). Tumor differentiation grades were G1 in 1 case (4.7 %), G2 in 14 (66.7 %), and G3 in 6 (28.6 %); data were missing for 14 patients. The median Ki67 proliferation index was 40 %. The median duration of follow-up was 6.4 months. Alpelisib was discontinued in 18 patients (51 %), including 6 (17.1 %) due to intolerable toxicity and 12 (34.2 %) due to disease progression. Median PFS was 9 months. Adverse events (AEs) were absent in 7 patients (20 %), while 16 (45.7 %) experienced AEs.
Conclusion. Our real-world data on mPFS align with global findings. Notably, the majority of patientsin this study received alpelisib in the 3rd–4th lines of therapy, reflecting their high pretreatment burden, which may have negatively impacted treatment efficacy. The most frequent AEs associated with alpelisib were hyperglycemia and skin reactions
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