e12589 Background: Better efficiency and safety of Nab-P is known to be due to the advantages of pharmacokinetics and pharmacodynamics of the drug. The fraction of unbound paclitaxel in plasma is 2.6-fold higher with Nab-P than with P. The purpose of the study was to assess efficacy and safety of Nab-P in ≥2nd lines of chemotherapy (CT) in patients (pts) with mBC with VC. Methods: Inclusion criteria: mBC with VC, ≥ 2 line of CT, HR+, HER2neu+ or triple negative type (TN), normal liver and renal function. Pts received Nab-P 260 mg/m2 q 21 days. Pts with Her2/Neu + received trastuzumab 6 mg/kg q 21 days. Results: 32 mBC pts, mean age 51.34 years (CI 35-76) were included. Among 32 pts Her2/Neu + had 5 (15.6%), TN – 9 (28.1%), HR+ 18(56.3%). 13(40.6%) pts received Nab-P as 2 line of CT, 13 (40.6%) pts, as 3-4 lines, 7(21.9%) as ≥5 lines. Pts were divided into 2 groups: group A - pts with VC 17(53.1%), group B - without VC 15(46.9%). Groups were comparable by age, number of previous CT lines, immunohistochemical types of BC. Group A had 2.47±0.32 CT lines (CV51.83%), including 8(47%) pts, who had received paclitaxel (P) in previous CT lines. Group B had on average 2±0.27 CT lines (CV53.03%). The objective response rate (ORR) was 37.5%(12 pts). In the group A ORR was 35.3% (6 pts). Out of 8 pts with VC, who had received P in previous lines, ORR was achieved in 3 pts (37.5%). In the group B ORR was 33.34%(5 pts). TTP was 6.8 mos (95% CI 6.1-13.7) for all pts, in the group A – 5.7 mos (95% CI 5.9-10.2), in the group B 6 mos (95% CI 6.5-13.7) (p = 0.046). Median 3-year OS of pts in group A was 18.9 mos (95% CI 4.3-22.4), in group B - 22.5 mos (95% CI 8.2-26.7) (p = 0.038). Toxicity did not differ significantly in pts in groups A and B and was manageable. Pts, who previously received P, had no new or severe toxicity. Conclusions: The data obtained confirms the possibility of Nab-P application in pts with VC. The use of Nab-P in pts treated with taxanes in previous lines is supposed for further study.

Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein‑4 (CTLA‑4) and programmed cell death protein‑1 (PD‑1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.

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Introduction. Erythropoietin (EPO) application is a pathogenetic method for anemia correction in cancer patients.The purpose of study. Clinical evaluation of the efficacy and safety of Eralfon® (epoetin alpha) in treatment for anemia in patients with malignant solid tumors during medical anticancer therapy.Materials and methods. We analyzed the data on anemia treatment with Eralfon® in 184 patients with malignant solid tumors receiving various medical anticancer therapies. Eralfon® was injected subcutaneously 12 000 IU 3 times per week or 40 000 IU once a week. Clinical antianemic effect, the time to maximum antianemic effect, adverse events (AE) were analyzed.Results. Patients were stratified by the grade of anemia, stages of treatment, presence of bone metastases, bleeding, previous medical and radiation anticancer therapies, dosage of Eralfon®. The time to effect was shorter in patients under 65. There were no significant differences in efficacy depending on the dosing regimen of Eralfon®. Efficacy was lower in patients with advanced tumors, especially in bone metastases. A history of tumor bleeding, chemotherapy and/or radiation therapy prolonged the period of hemoglobin recovery to normal values. Arterial hypertension and venous thrombosis were the most common AE associated with Eralfon®. Eralfon® 12 000 IU 3 times per week caused less frequent complications, with no cases of ossealgia and myalgia.Conclusion. Eralfon® demonstrated clinical efficacy in treatment for anemia in patients with solid malignant tumors receiving medical anticancer therapy. Dosage of 12 000 IU 3 times per week provided better control of the antianemic effect and adverse events.

Patients with brain metastases of HER2-positive breast cancer (BC) is a special group of patients who are difficult to treat and have a short life expectancy. The possibilities of whole brain radiotherapy, stereotactic radiosurgery and surgery in such patients are rather limited. Trastuzumab emtansine (T-DM1) showed potential activity in this subset of patients. T-DM1 is an antibody-chemical conjugate (ADC) that delivers directly to HER2-positive cancer cells, thereby limiting damage to healthy tissue. At this point, the efficacy of trastuzumab emtansine has been demonstrated in several randomized trials as a second and subsequent lines of therapy for advanced breast cancer with a favorable toxicity profile of the drug. This article describes a clinical case of a patient with luminal B HER-2 positive breast cancer who, underwent stereotactic radiosurgery and was treated with trastuzumab emtansine as a the second line of treatment for disease progression with metastatic brain lesions after trastuzumab/pertuzumab-containing therapy. Partial regression of metastases with long-term duration of the effect was achieved treatment with trastuzumab emtazine has been being continued for 24 months. Tolerability of therapy was good: thrombocytopenia 2 degree was the main among side effects. The effect has been persisted for 2 years and the patient continues the treatment. Discussion of the results of real clinical practice with well-known studies was carried out.