Experience of therapy with CDK4/6 inhibitors in patients with PIK3CA mutation and HER2-low luminal Her2- mBC of the Kazakh population in real clinical practice

Abstract

Relevance. Hormonal therapy (HT) in combination with CDK 4/6 inhibitors is a standard treatment for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC). Study objective. Improving treatment outcomes for patients with HR+ Her2- mBC. Materials and methods. The study included 400 patients with hormone-positive (HR+) Her2- mBC who received combination therapy (iCDK4/6+HT) from January 2019 to January 2024. A total of 182 tumor samples were analyzed, DNA was isolated using the GeneJET FFPE DNA Purification Kit. Amplification and detection of results were performed using the PIK3CA Mutation Analysis Kit for Real-Time PCR (Entrogen) consisting of the E542K, E545K, E545Q, H1047R, H1047L mutation spectra. Results and discussion. Response duration to progression (months): 1 line - up to 43 months. 2 line - up to 35 months. 3 line and more - up to 12 months. Of the 182 patients, 36 (19.8%) were found to have various mutations in the PIK3CA gene. The three most common missense substitutions in the PIK3CA gene were p.H1047R-18 (50%), mutation p.E542K-9 (25%), and mutation p.E545K-7 (19.5%). Another mutation p.H1047L was found in 2 cases (5.5%), and the mutation p.E545Q was not detected. 13 patients with PIK3CA mutation received CDK4/6 inhibitors in combination with HT in the 2nd and 3rd lines, the median time to progression was 4 months compared to the group of patients without mutation (the median time to progression of therapy in the 2nd and 3rd lines is 12 months). Conclusion. The use of combination therapy iCDK4/6 + HT in earlier lines for HR+ Her2-metastatic breast cancer demonstrates its efficacy, which is confirmed by a longer response before disease progression. The study showed that PIK3CA mutation led to a decrease in the median time to progression in patients receiving CDK4/6 inhibitors (5 months versus 12 months). This confirmed the theory of the negative impact of PIK3CA mutation on the outcomes of hormonal therapy.

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