Alpelisib for the treatment of HR+HER2-metastatic breast cancer in patients with  the PIK3CA mutation: results of the SOLAR-1 study

Semiglazova, Tatiana; Семиглазов, В. В.; Клименко, В. В.; Brish, N.A. Brish; Alekseeva, Yu. V.; Klyuge, V.A. Klyuge; Krutov, Anton; Палтуев, Р. М.; Kasparov, Boris; Krivorotko, Petr; Семиглазов, В. Ф.

doi:10.18565/pharmateca.2020.7.15-23

Cited by 4 publications

(1 citation statement)

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“…Мутация гена PIK3CA является причиной повышенной активации PI3K, которая стимулирует рост и деление раковых клеток [ 8 ]. Блокада PI3K с помощью препарата алпелисиб позволяет контролировать этот процесс, однако сопровождается развитием нежелательных явлений (НЯ), наиболее частым из которых отмечается гипергликемия [ 9 ].…”

Section: актуальностьunclassified

Toxic manifestations of alpelisib in endocrinology. Description of the clinical case

Kudaeva,

Kozhedub,

Kupryshina

et al. 2023

Probl Endokrinol (Mosk)

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Breast cancer (BC) is a serious disease and is considered an important health problem worldwide. The prevalence of the disease in women according to Rosstat was 64,951 cases in the Russian Federation in 2020 (21.7% among all types of cancer). Hormone-dependent estrogen receptor-positive (HR+), human epidermal growth factor receptor type 2 negative (HER2-) metastatic breast cancer (mBC) accounts for 70% of all cases. About 40% of patients with ER+/HER2- mBC have mutations in the PIK3CA gene, leading to hyperactivation of the alpha isoform (p110α) of phosphatidylinositol 3-kinase (PI3K). Hormonal therapy with or without cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is considered the standard treatment for patients with ER+/HER2- mBC. However, acquired resistance to this therapy remains a problem. Innovative methods for the treatment of breast cancer are the use of targeted therapeutic agents aimed at direct inhibition of the PI3K pathway in combination with hormone therapy. Alpelisib is a PI3Kα-specific inhibitor. Hyperglycemia is the most common side effect of alpelisib treatment. Currently, there is a consensus on the prevention and correction of hyperglycemia in patients receiving therapy with alpelisib, which recommends that before starting therapy, in order to diagnose carbohydrate metabolism disorders and assess the risk of developing hyperglycemia, determine in all patients: the level of glycated hemoglobin (HbA1c), glucose fasting plasma (FPG), body mass index (BMI). And also to evaluate such risk factors as the presence of a family history of type 2 diabetes mellitus (DM 2), the presence of gestational diabetes in the patient’s history, or the fact of the birth of children weighing more than 4 kilograms.Recently, new combinations of drugs have been actively used to treat disorders of carbohydrate metabolism, such as pioglitazone + metformin. This paper discusses the mechanism of action of PI3K inhibitors, new therapeutic combinations and their undesirable effects, and presents therapeutic experience.

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Section: актуальностьunclassified

Toxic manifestations of alpelisib in endocrinology. Description of the clinical case

Kudaeva,

Kozhedub,

Kupryshina

et al. 2023

Probl Endokrinol (Mosk)

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Inhibitors of cyclin-dependent kinases 4/6 for breast cancer patients with different somatic mutations of the PIK3CA gene

et al. 2020

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Introduction. Breast cancer is the leader in cancer incidence in theRussian Federation. The tumor is considered extremely heterogeneous and the luminal subtypes of breast tumors occupy a special place, since they are considered relatively favorable in therapy and control of the disease.Drug therapy for hormone-positive cancer has undergone significant evolution and new anticancer agents have appeared in the arsenal of the oncologist and have shown promising results compared to classical therapy. The search for predictive markers of the effectiveness of new therapy has become of great importance. This marker turned out to be a mutation in the PIK3CA gene – one of the most frequent genetic disorders in breast cancer cells. According to the literature, the presence of this mutation negatively effects on endocrine therapy for breast tumors.The aim of this study was to analyze the frequency of mutations in the PIK3CA gene among patients with hormone-positive tumors, and the effectiveness of therapy with CDK4/6 inhibitors in this group of patients.Materials and methods. The material for the study of the mutation in the PIK3CA gene was tumor biopsies of 31 patients and clinical data on the response to therapy with CDK4/6 inhibitors and classical hormone therapy.Results and discussion. The results of the work showed a high incidence of the PIK3CA mutation among hormone-positive tumors (45%). The mutation resulted in a decrease in both the median time to progression after radical surgery (from 48.4 ± 7.8 months to 30.1 ± 6.0 months) in patients receiving adjuvant hormone therapy and progression-free survival in patients receiving therapy with CDK4 /6 inhibitors (4.2 months versus 9 months). This confirmed the theory that the PIK3CA mutation negatively affects the outcome of hormone therapy.Conclusions. PIK3CA is an important predictive marker in endocrine therapy for hormone-positive tumors. Its presence not only determines the relatively worse results of treatment, but can also serve as an indication for the appointment of a special series of drugs – inhibitors of this mutation.

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The consensus on the prevention and correction of hyperglycemia in patients with HR+ HER2- metastatic breast cancer treated with alpelisib

et al. 2021

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The consensus on the prevention and correction of hyperglycemia in patients with HR+ HER2- metastatic breast cancer treated with alpelisib was developed by the experts of the Russian Association of Endocrinologists and the Russian Society of Clinical Oncology. The consensus contains recommendation on risk assessment, prophylaxis and correction of hyperglycemia regarding the baseline metabolic status of the patients.

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Alpelisib for the treatment of HR+HER2-metastatic breast cancer in patients with the PIK3CA mutation: results of the SOLAR-1 study

Cited by 4 publications

References 0 publications

Toxic manifestations of alpelisib in endocrinology. Description of the clinical case

Toxic manifestations of alpelisib in endocrinology. Description of the clinical case

Inhibitors of cyclin-dependent kinases 4/6 for breast cancer patients with different somatic mutations of the PIK3CA gene

The consensus on the prevention and correction of hyperglycemia in patients with HR+ HER2- metastatic breast cancer treated with alpelisib

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