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Introduction. Сombination of alpelisib plus fulvestrant is approved in patients with hormone receptor positive, HER2-negative, PIK3CA-mutated advanced breast cancer (ABC) after progression on hormonotherapy. Efficacy data of alpelisib in heavily pretreated patients with HR+/HER-2-, PIK3CA-mutated advanced breast cancer are limited, only results from phase I trial are available. Here we report our results of alpelisib efficacy in 19 heavily pretreated patients.Object: to evaluate efficacy and safety of combination alpelisib plus fulvestrant in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer in initial and later lines of therapy in real clinical practice.Materials and methods. Combination of alpelisib plus fulvestrant was investigated in 19 patients with HR+/HER2-, PIK3CAmutated ABC, alpelisib at a dose of 300 mg per day plus fulvestrant at a dose of 500 mg i.m. every 28 days and once on day 15. Treatment continued until disease progression or unacceptable toxicity.Results. From February 2021 19 patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer were treated with alpelisib plus fulvestrant. The data cut off is October 2021. Median lines of treatment in advanced disease was five, including 19 (100%) patients received CDK4/6, 14 (74%) – fulvestrant and/or everolimus and 15 (79%) – chemotherapy. 4 (21%) received alpelisib in a second line, 15 (79%) – in subsequent lines. Median progression-free survival was 7 months. The response was evaluated in 18 patients: partial response was achieved in 5 (28%) patients, stable disease – in 9 (50%), disease progression – 4 (22%). The most frequent adverse events were hyperglycemia – 74% (grade 3 – 22%), creatinine increased – 42% and rash – 37% (grade 3 – 22%). Only one patient has discontinued the treatment due to Quincke`s edema.Conclusions. Combination of alpelisib with fulvestrant is an effective option both in initial and later lines of therapy in patients with HR+/HER2-, PIK3CA-mutated advanced breast cancer including fulvestrant, CDK4/6 inhibitors and/or everolimus – pretreated 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

Understanding of cancer biology is at the cornerstone of design of new and effective treatment strategies. Identification of molecular drivers of tumor growth and progression allow identify right patient for the right treatment for personalized treatment plan optimization. Breast cancer (BC) encompasses a heterogeneous collection of neoplasms with diverse morphologies, molecular phenotypes, responses to therapy, probabilities of relapse and overall survival. Molecular and histopathological classification aims to categories tumors into subgroups to inform clinical decisions, to improve long-term treatment results and maintain the quality of life of this group of patients. Germinal mutation in the BRCA1/2 (BRCAm) genes in a tumor determines the hereditary predisposition, disease manifestation, therapeutic options and clinical efficacy. Therefore, patients withBRCAmBCrepresent a special subgroup requiring personalized treatment approach.Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is a targeted therapeutic agent that acts as inhibitor of single-strand breaks reparation, leading to their accumulation, conversion to double-strand breaks and eventually to cancer cell apoptosis. Olaparib is a first-in-class PARP-inhibitor with an outstanding antineoplastic activity known for some malignant tumors, demonstrates effectiveness and safety of therapy inBRCAmBCas well. The results of OlympiAD and LUCY trials are represented in the article. Subgroup analysis may define the patient population that would benefit from PARP inhibitors therapy.

The survival of patients even with disseminated disease reached 7–8 years after introduction of imatinib and sunitinib for the treatment of gastrointestinal stromal tumours (GIST) into everyday clinical practice. These drugs efficacy is largely determined by the presence and any mutations of C-KIT and PDGFR genes. It was established that new mutations appear in most tumours against the background of tyrosine kinase inhibitors therapy, which causes the development of secondary resistance and the progression of the disease in most cases. The search for opportunities to overcome the newly developed or initially existing resistance caused by different gene mutations continues to be of vital importance. One of such drugs is regorafenib, which has demonstrated antitumour activity against progression on imatinib and/or sunitinib. The paper reviews the studies of the efficacy of regoraphanib in patients with disseminated GIST, taking into account the presence and any mutations of C-KIT and PDGFR genes, and presents a description of their own clinical case of prolonged use of the drug in a patient who have received earlier both imatinib and sunitinib.

Background. Working out of the second line chemotherapy of advanced gastric adenocarcinoma is a promising approach to cancer therapy. Ramucirumab, an anti-angiogenic agent specifically targeting vascular endothelial growth factor receptor-2 (VEGFR-2). In April 2014, the FDA approved ramucirumab as a single agent or in combination with paclitaxel for treatment of advanced gastric or gastroesophageal junction adenocarcinoma that has progressed on or after prior fluoropyrimidineor platinum containing chemotherapy based on data of REGARD and RAINBOW trials.Materials and Methods: From June 2016 to 15Jan 201837 pts with advanced GC were treated with ramucirumabin the second line treatment as single agent (11 pts) or in combination with paclitaxel (26 pts) in N.N.Blokhin National medical research center of oncology.Results: edian PFS (MPFS) and median OS (MOS) was 1,8 and 7,6 mons for monotherapy group. For combination group MPFS was 4,0mons, MOS -10,6 mons. Ramucirumab had an acceptable safety profileConclusions:ur data are similar to the data of international randomized trials.

Molecular and biological features of triple negative breast cancer (TN BC) determine the limited possibilities of systemic therapy and, as a consequence, the more aggressive course of the disease. Taxanes are one of the most effective chemotherapies used in breast cancer therapy. The special form of paclitaxel nab-paclitaxel makes it possible to obtain an objective and a subjective effect, which is especially important in the pre-treated patients. In addition, the drug has a favourable safety profile and a well-controlled toxicity.The article contains a review of the literature on the prospects for the use of nab-paclitaxel in breast cancer, especially in its triple negative version, and a description of the clinical case of therapy with a combination of cisplatin and nab-paclitaxel in a young patient with BRCA-1-associated TN breast cancer.

The HannaH study showed that neoadjuvante-adjuvant subcutaneous and intravenous trastuzumab have similar efficacy and tolerability in patients with early HER2-positive breast cancer. The analysis of the results of the subcutaneous and intravenous trastuzumab usage in Russian population showed the favorable association between tpCR anf EFS. tpCR achiviement is associated with clinical benefit in HER2 positive breast cancer. For patients with difficult venous access who do not require intravenous chemotherapy currently, Subcutaneous trastuzumab allows to receive effective treatment without the risk of complications, which involves catheterization of a Central vein.