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.

Introduction. The presence of a germinal BRCA mutation occurs in 3–4% of all breast cancer (BC) patients with various biological subtypes, but significantly with a high frequency in patients with a triple negative biological subtype (in 10–20% of cases). For the treatment of patients with HER2-negative metastatic breast cancer associated with gBRCA mutation, the effectiveness of biologically targeted drugs from the group of PARP inhibitors (olaparib and talazoparib) has been proven.Purpose. Comparison of the results of our experience with the use of talazoparib in patients with HER2-gBRCA+ + mBC with the data of the EMBRACA registration study.Materials and methods. As part of the multicenter compassionate use program (CUP) with the support of Pfizer, 24 patients with HER2-negative metastatic gBRCA-associated mutation metastatic breast cancer (HER2-gBRCA+ breast cancer) received biologically targeted therapy with the PARP inhibitor talazoparib at a standard oral dose of 1 mg per day for vital indications . The average age of patients with HER2-gBRCAm+ breast cancer was 50 years (29–90 years).Results. Objective response (OR) was registered in 29% of cases, disease control (OR+stabilization) – in 71% of cases. The median progression-free survival (PFS) was 6.5 months (95% CI [3–10]). Objective response, disease control, and median PFS were evaluated depending on the biological subtype, the number of lines of previous therapy, and the presence of platinum-containing agents in the anamnesis.Objective response and disease control were evaluated depending on the biological subtype: in patients with ER+HER2-mBC versus patients with triple negative subtype, OR was 33% vs 22%, and disease control was 83% vs 61%, respectively. In the presence of < 3 vs ≥ 3 lines of therapy for metastatic disease in the anamnesis, OR was 31% vs 12.5%, disease control – 75% vs 50% of cases, respectively. In the presence or absence of platinum-containing agents in the anamnesis, OR was observed in 22% vs 33% of cases, and disease control – 67% vs 67%, respectively.In patients with the luminal subtype versus patients with the triple negative subtype, the PFS was 9 months vs 5 months, respectively (HR = 0.705; 95% CI [0.231–2.147]; p = 0.5208). Median PFS in the presence of <3 vs ≥3 lines of therapy for metastatic disease in the anamnesis was 9 months vs 4 months, respectively (HR = 4,216; 95% CI [1,334–13,327]; p = 0.0056). In the presence or absence of platinum-containing agents in previous lines of therapy 5 months vs 9.5 months, respectively (HR =1.484; 95% CI [0.48–4.582]; p = 0.4750).During the treatment with talazoparib adverse events of the 3rd-4th grades were observed in 5 patients (20,8%). These include moderate and severe anemia in 3 patients (12.5%), thrombocytopenia in 1 patient (4%), and neutropenia in 1 patient (4%). The majority of patients (79,5%), which received talazoparib, did not require dose adjustment. The need to reduce the dose to 0.75 mg was noted in 3 patients (12.5%), to 0.5 mg – in 2 patients (8%). Hemotransfusion was performed in 3 patients. For effective therapy safety management regular monitoring of blood parameters is necessary.Conclusion. Thus, targeted therapy with talazoparib is an effective treatment option for HER2-gBRCA+ mBC.

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Triple-negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer. In the presence of distant metastases, the median overall survival does not exceed 14 months. TNBC is an extremely heterogeneous group of tumors, it includes both tumors extremely sensitive to chemotherapy and tumors that require targeted or immunotherapy for the best treatment outcomes. Such subtype features make it difficult to develop a single treatment strategy for all patients. Current perceptions of resistance mechanisms and molecular drivers progression have increased therapeutic opportunities for metastatic TNBC (mTNBC). For example, in the last few years, checkpoint inhibitors and PARP inhibitors have entered into clinical practice in the Russian Federation. This review presents clinical trial data, as well as an algorithm for choosing therapy for patients with TNBC, based on the results of recent clinical studies. The review focuses mainly on drugs registered at the territory of the Russian Federation, that allows to apply these options in everyday clinical practice. Promising directions therapy of mTNBC not registered at the territory of the Russian Federation yet will be showed in a separate review in the next issue in the Journal of Modern Oncology.

The consensus on the prevention and correction of rash in patients with HR+ HER2- metastatic breast cancer treated with alpelisib was developed by the experts of the Russian Society of Clinical Oncology and dermatovenerologists. PIK3CA mutation is a poor prognostic factor for HR+ HER2- metastatic breast cancer. Alpelisib demonstrates efficacy in patients with PIK3CA mutation, but treatment might be associated with adverse events that include rash. All-grade rash was reported in 35.6% patients in SOLAR-1 trial (n=284). According to the published real-world data, for Russian population (n=19) all-grade rash was reported for 37% patients. The consensus contains practical recommendation on management of patients with rash of different grade.