An multidisciplinary advisory board meeting was held in Moscow on November 27, 2021 to discuss different issues of early diagnosis and assessment of lung cancer prevalence (staging) by country's leading specialists in the field of lung cancer diagnosis and treatment. We would like to present to your attention the Expert Panel's opinion.

Introduction. The addition of durvalumab after chemoradiation therapy in unresectable stage III non-small-cell lung cancer (NSLC) is a new standard of care.

Aim. Study the features and outcomes of durvalumab maintenance treatment after chemoradiotherapy in patients with unresectable stage III NSCLC in the real-world clinical practice in Russia.

Materials and methods. 50 patients with unresectable III stage NSCLC after concurrent or sequential chemoradiotherapy (CRT) were enrolled in this observational retrospective study. Median follow up time at primary analysis was 12.4 months.

Results. A mean age of the patients in the study was 61.2 years (58.4-64.1; 95% CI). Most of the patients had received sequential CRT (76%, n = 38). Median time of durvalumab start from the end of CRT varied from 22 to 50 days (overall - 35 days). Estimated median PFS and OS were 10.86 months (7.78-14.01, 95% CI) and 26 months (20.19-31.81, 95% CI), respectively. There was a trend toward increased PFS in patients with smoking history: 12 months (9.79-14.2; 95% CI) versus 4,9 months (0.0-12.47; 95% CI), p = 0.2. Half of the patients without smoking history (5/10) had targetable mutations (EGFR ex 19, ALK, ROS1, cMET). Most common reported adverse events of special interest were pneumonitis grade 1-2 (36%, n = 18), leading permanent treatment discontinuation to in 6% of patients (n = 3). There were no reported cases of grade 3-4 adverse events.

Conclusions. Real-world characteristic of patients in our study were different from PACIFIC trial. Sequential CRT is the most frequent treatment option in locally advanced unresectable NSCLC in Russia. Estimated PFS was shorter than in PACIFIC, but there were less cases of pneumonitis.

Introduction. PARP inhibitors demonstrated high efficacy in BRCA1/2-associated Her2-negative metastatic breast cancer (BC). They were included in the current standard chemotherapy regimen and recognized as a priority option for the treatment of such tumours following the results of clinical studies.

Aim. Review the experience with talazoparib (Talzenna) in the real-world clinical practice of 6 medical centers in Russia.

Materials and methods. The review included data from 29 patients with HER2-negative metastatic breast cancer associated with a gBRCA mutation, who have been receiving talazoparib therapy in 6 medical centers of Russia since April 2021. Talazoparib was given at the standard dose 1 mg once daily, the dose was reduced, if any adverse event developed.

Results. The median age of the patients was 50 years. 23 patients had a BRCA1 mutation, 5 patients had a BRCA2 mutation and one of the patients had a PALB2 mutation. Prior to starting talazoparib therapy, patients had received up to 9 lines of therapy for metastatic disease, the median was 1 line. The median follow-up period at that time was only 4.6 months. The median recurrence-free survival (RFS) was not reached. Progression was observed in 10 patients with a treatment period of 1 to 7.5 months, 19 patients continued to receive PARP inhibitor therapy without signs of disease progression, with a treatment period of 2 to 18 months. The objective response rate (ORR) was 57.2%, the clinical efficacy was confirmed in 85.7% of cases. The subgroup analysis showed that the lowest efficacy of therapy was reported in the group of patients, who had received prior therapy with platinum-based drugs, the median progression-free time (mPFT) was 4.5 months. (95% CI: 1.79-9.2). While for patients who had not received the prior platinum drug regimens, the median was not reached. Haematologic toxicities were common adverse events (AEs) for the talazoparib therapy, which were reported in 34.5% of cases. Transfusions of blood components were required in 3 patients, one of them required them repeatedly. All dose modifications were due to hematological toxicities. 7 patients (24.1%) required a dose reduction and 3 patients (10.3%) - repeated dose reduction.

Conclusions. Testing for BRCA1/2 mutations in Her2-negative mBC should be a mandatory diagnostic procedure. Talazoparib therapy is an effective and safe treatment option for patients with gBRCAmut HER2-mBC.

Introduction. Current treatment of metastatic luminal Her2-negative breast cancer includes combination of endocrine therapy (ET) with CDK4/6 inhibitors. This type of therapy demonstrated impressive efficacy over mono ET in early lines of treatment in phase III randomized clinical trials. Treatment patterns in real clinical practice (RCP) are of great interest. We represent the first available local data for all CDK 4/6 inhibitors in RCP in Russian Federation in accordance with the number of patients (pts).

Aim. Analysis of the patterns of palbociclib administration in RCP.

Materials and methods. One hundred and 5 pts from 12 regions of Russian Federation were included in this analysis and received palbociclib in combination with ET from 2017 to 2020. Median age was 57 years (29-75), 31/105 (29.5%) of pts were < 50. De novo metastatic disease was observed in 16 (15.2%) pts, 89 pts progressed after radical treatment. Visceral metastases (mts) at palbociclib initiation had 61/105 (58.1%) of pts.

Results. Only 22/105 (21%) of pts received palbociclib as 1st line treatment of metastatic disease. The majority of pts was treated with palbociclib in 2nd and 3rd lines (28.5% and 30.5% respectively). In 26/105 (24.8%) pts palbociclib was combined with aromatase inhibitors, in other cases - with fulvestrant. Median follow-up time was 6.5 (1.1-31.9) months, median progression free survival - 6.0 (1.0-28.0) months. Most common adverse events (AE) were leukopenia, neutropenia and thrombocytopenia. Only in 3 cases palbociclib was completely stopped due to toxicity.

Conclusions. Our data indicates that there is a need to move palbociclib initiation in first two lines of treatment to get maximal improvement in survival and to increase its usage in young women.

In less than 10 years, the standard of drug therapy for non-small cell lung cancer (NSCLC) has changed tremendously. The emphasis on a personalized approach in the choice of treatment tactics in patients with advanced NSCLC yields tangible results. The identification of patients with activating mutations and the administration of targeted therapy to them has significantly improved the results of treatment. Translocations in the ALK gene are classified as rare mutations. As a rule, these are quite young people, non-smokers or with little experience of smoking. One of the characteristic features of ALK-positive NSCLC is frequent metastasis to the CNS, so one of the important criteria for the effectiveness of new drugs is the assessment of their intracranial activity. Lorlatinib is a third-generation tyrosine kinase (TKI) ALK that penetrates the blood-brain barrier well and has a wide spectrum of antitumor activity against most known resistance mutations that appear during targeted therapy with crizotinib and second-generation TKI. Like its predecessors, lorlatinib was initially approved for second- and third-line use in patients already treated sequentially with crizotinib and one of the second-generation drugs, or starting their treatment with a second-generation TCT. After the publication of the results of the randomized comparative study CROWN, which demonstrated a convincing advantage of the drug compared to crizotinib in the first line of treatment, its high intracranial activity, the indications were expanded. Currently, lorlatinib is registered in the Russian Federation for use in ALK-positive patients with advanced non-small cell lung cancer (NSCLC), both those who have already received targeted therapy for first and/or second generation ALK TKIs, and in untreated patients.

For patients with the metastatic subtype of luminal HER-2-negative (HR+/HER2-) breast cancer (mBC) in the absence of visceral crisis, the gold standard of treatment is a combination of CDK4/6 inhibitors and aromatase inhibitors, regardless of their menopausal status and the sites of metastasis. The effectiveness of this approach was confirmed in the MONARCH, PALOMA, MONALEESA study cycles for the drugs abemaciclib, palbociclib and ribociclib, respectively. Metastasis in the central nervous system (CNS) in breast cancer complicates the treatment of patients and leads to the search for new approaches to the choice of therapy. To date, neurosurgical and radiosurgical techniques are actively used, however, drug therapy still stands for the leading positions. Data on the use of CDK4/6 inhibitors or aromatase inhibitors in patients with CNS metastases are limited. Most studies did not include patients with CNS metastases, only PALOMA-2,3 and MONALEESA-3 studies allowed the inclusion of patients with either “inactive” CNS metastases or after exposure to local treatment methods (for example, radiosurgery, radiotherapy, or surgery). In the study of real clinical practice of combined endocrine therapy with ribociclib (CompLEEment-1) allowed the inclusion of patients with active brain metastases (n = 51), while the subgroup analysis demonstrated the benefits of using a combination of ribociclib and aromatase inhibitors in patients in this difficult clinical situation. In the article, the authors review the available data from randomized clinical trials and real clinical practice, and also illustrate with their own observation.

The “state-of-art” treatment approach for patients with metastatic urothelial cancer (eg, bladder cancer or other urothelial tumors of urinary tract) is platinum-containing chemotherapy, however, despite the high immediate efficacy of therapy (up to 70% of the objective response rate), long-term results of treatment remain unsatisfactory, median progression-free and overall survival usually do not exceed 6 and 12 months respectively, patients with visceral metastases or poor performance status have a particularly dismal prognosis. The most effective treatment for this disease is cisplatin-containing chemotherapy, ddMVAC (methotrexate, vinblastine, doxorubicin, cisplatin) and GC (gemcitabine, cisplatin) regimens are most effective, however, in real world setting a minority of patients can tolerate these treatment options. Recent advances in the treatment of urothelial cancer are associated with discoveries in the field of immunotherapy for this disease by targeting the PD-1/PD-L1 pathway. The most promising results in the first line of treatment for this disease based on the sequential use of cisplatin-containing chemotherapy with maintenance avelumab therapy, the latter drug has been proven to increase the overall survival of patients with metastatic urothelial cancer. This article discusses key data on the immediate and long-term effectiveness of systemic therapy for metastatic urothelial cancer, as well as potential ways to improve the results of treatment of patients with this disease, primarily through the introduction of maintenance immunotherapy into real world clinical practice and expanding the category of patients who are eligible for platinum-containing chemotherapy.

Introduction. Nowadays the standard of care for locally advanced and metastatic urothelial carcinoma (UC) is a combination of platinum-based drugs. However, such a therapy is characterized with high toxicity and selective efficacy. So, the question of the optimal alternative to the first line of therapy and the choice of drugs for the second line of therapy is currently relevant.

Immune checkpoint inhibitors have revolutionized the treatment of UC. Nevertheless, despite the fact that initially the drugs of this series showed a fairly high efficacy as a second-line therapy for metastatic UC, at present there is no unambiguous opinion about the correct tactics of their use. There is also no consensus on the predictive value of PD-L1 biomarkers and their significance in determining treatment tactics.

Aim. To evaluate the efficacy and tolerability of first-line atezolizumab therapy in 22 patients with unresectable forms of UC.

Materials and methods. The experience of the State Clinical Hospital named after D.D. Pletnev on the example of 22 patients with advanced UC who received first-line therapy with atezolizumab 1200 mg intravenously once every 21 days until progression or intolerable toxicity. Efficacy was assessed according to RECIST 1.1 criteria.

Results and discussion. Median follow-up 16.3 months. The objective response rate (ORR) is estimated at 72.7%, 95% CI. A complete response according to RECIST 1.1 criteria was observed in 5 patients (22.7%). Median time to first response was 2.2 months (range 1.5-5.7), late responses (at 5 and 5.7 months) required space in 2 patients. Median progression-free survival was 5.2 months (95% CI) in all patients. Median overall survival (OS) 18.5 months (95% CI). Specific application-related events were required in 10 (45.4%) cases. All the side effects were managed by standard symptomatic therapy. The dosage of atezoli-zumab was reduced in 7 (32%) cases. Immune-mediated adverse events were reported in 5 (23%) patients. No patient received systemic non-corticosteroid immunomodulatory agents for immune-mediated events. 2 (9%) patients received corticosteroids.

Conclusions. Atezolizumab has shown high efficacy in the first line of treatment for advanced UC.

In recent years, the approach to the treatment of advanced renal cell carcinoma (RCC) has undergone significant changes. The introduction of targeted drugs in the systemic therapy of RCC in the 2000s began with tyrosine kinase inhibitors that replaced cytokines and had a revolutionary effect. Then the therapeutic arsenal was expanded with the introduction of doublets consisting of a combination of immune checkpoint inhibitors or immune checkpoint inhibitors and tyrosine kinase inhibitors. Tyrosine kinase inhibitors continue to represent an effective treatment option for metastatic RCC (mRCC), maintaining their position as first-line therapy in patients with a favorable prognosis. According to the CheckMate study, targeted therapy is highly effective, and the incidence of complications is generally lower than with nivolumab/ipilimumab combination therapy. Unlike dual immunotherapy, sunitinib does not expose patients with a favorable prognosis to undue risk of adverse events, while leaving more options for subsequent lines of therapy, and it's also often more cost-effective. The presented clinical observation is an example of successful monotherapy with sunitinib in a previously untreated mRCC patient with a favorable prognosis. This case is of particular interest due to the lesion of a single kidney and the patient's polymorbidity. Effective targeted therapy in the postoperative period had a positive effect on the quality and life expectancy.

Anemia is one of the most common symptoms of hematological malignancy and, on the other hand, a common complication of myelosuppressive anticancer therapy. Iron, vitamin B12, folate, biological analogs of human erythropoietin (EPO), and new targeted drugs (lenalidomide, luspatercept, roxadustat, etc.) are used in clinical practice to correct anemic syndrome in cancer patients. All these activators of erythropoiesis are combined into a single group called erythropoiesis-stimulating agents (ESAs). Issues of physiological regulation of erythropoiesis, historical information on the creation of recombinant human erythropoietin (rh-EPO), structural and biological characteristics of this group of drugs are covered in this literature review. In accordance with ESMO guidelines (2018), rh-EPO is indicated for patients receiving myelosuppressive chemotherapy with symptomatic anemia with Hb < 100 g/L and asymptomatic anemia with Hb < 80 g/L. ESAs are not used in patients not receiving chemotherapy, similarly to ASCO/ASH (2019) guidelines. Iron replacement therapy in patients receiving rh-EPO should be used regardless of whether there is an initial iron deficiency or not, since its functional deficiency occurs during treatment. The low-risk MDS is exception, where rh-EPO may be the mainstay of therapy. Low-risk MDS patients with endogenous EPO levels < 500 mIU/mL and a low transfusion load of less than 2 RBCs per month are optimal candidates for rh-EPO therapy. The article is illustrated by clinical observation of a patient with R-IPSS intermediate-risk MDS treated with epoetin alfa. The problems of prevention of thromboembolic complications associated with the use of ESA are also discussed.

Introduction. Thanks to scientific advances and discoveries in the study of tumor cell biology, new effective drugs for the treatment of chronic lymphocytic leukemia/ small lymphocytic lymphoma have emerged. Currently, there are drugs with different application points at the molecular level. One such drug is acalabrutinib, which is a selective second-generation inhibitors of Bruton tyrosine kinase and has a more favorable toxicity profile.

Objective. To evaluate the efficacy of acalabrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.

Materials and methods. Since February 2020 acalabrutinib (100 mg 2 p/day orally) has been administered to 7 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (mean age 64 years) at the Hematology Research Center. Six patients received acalabrutinib in 1st-line therapy and one patient received acalabrutinib in 2nd-line therapy. The mean comorbidity index (CIRS) of the patients was 10 points (range, 8 to 14). Most patients had at least one of the adverse prognostic factors - IGHV nonmutated gene status, TP53 gene aberration (del17p13 and/or TP53 gene mutation), complex karyotype disorders.

Results. All patients achieved partial remission of the disease (overall response 100% in the form of regression of B-symptoms, lymphocytic leukocytosis, splenomegaly) at the control period of treatment with acalabrutinib +12 months. The most frequent adverse events when taking acalabrutinib were the occurrence of headache in the first month of taking the drug, spontaneous subcutaneous hematomas. No hematologic toxicity, infectious complications, or cardiac complications were noted. At a median follow-up of 34 months, no patient showed disease progression.

Conclusions. The selective Bruton tyrosine kinase inhibitor acalabrutinib has demonstrated high efficacy in patients with adverse risk factors, good tolerability and minimal toxicity, including in comorbid patients.

Nausea and vomiting are the most frequent and painful adverse event of chemotherapy. Uncontrolled nausea and vomiting lead to a significant decrease in the quality of life of patients, nutritional insufficiency, breaking of the chemotherapy therapy regimen. Nausea and vomiting worsen the result of chemotherapy and the prognosis of the disease. In clinical studies of antiemetic drugs the “complete response” is used as the primary endpoint. The complete redponse is the absence of nausea and vomiting and the need for additional antiemetic drugs. The oral combination of netupitant and palonosetron is a modern drug for the prevention of nausea and vomiting induced by chemotherapy. This combination includes a highly selective anatagonist of NK1-receptors netupitant at a dose of 300 mg and an antagonist of 5-HT3 receptors palonosetron at a dose of 0.5 mg. The combination of net-upitant and palonosetron has high compliance, it is prescribed once before chemotherapy. The combination of netupitant and palonosetron makes it possible to achieve complete control of acute (0-24 hours) and delayed (24-120 hours) nausea and vomiting with highly emetogenic chemotherapy. In a randomized trial (n = 1455) with AC chemotherapy (doxorubicin + cyclophosphamide), the combination of netupitant and palonosetron resulted in a complete response during the general phase (0-120 hours) in 73.3% of patients. 78.4% of patients with the combination of netupitant and palonosteron experienced “no effect on daily life” due to nausea and vomiting. In an observational study of real clinical practice (n = 1197), the combination of netupitant and palonosetron in the AC chemotherapy regimen (doxorubicin + cyclophosphamide) had a complete response during the general phase (0-120 hours) in 81% of patients. Adverse events when using the combination of netupitant and palonosetron are minimal, constipation was noted in 1-8% of cases, headache in 1.4-3.6% of cases.

Nowadays radiotherapy is one of the main methods of cancer treatment. According to the WHO, more than 50% of patients with diagnosed malignancies need radiation therapy. However, there are a number of side effects of the latter, which are as much the task of the radiotherapist as the actual treatment of the tumor. Skin reactions are one of the most common side effects of radiation therapy, affecting up to 85-95% of patients. Radiation dermatitis is a unique pathology compared to other forms of skin damage, such as traumatic, because the radiation spreads from the epidermis to the deep tissue layers consistently. Such skin reactions can cause some discomfort in cancer patients and even real problems, including interruptions in treatment, decreased aesthetic appeal and decreased quality of life. Recent technological advances and new radiodermatitis treatment regimens represent an opportunity to alleviate the side effects of radiation therapy. Despite a variety of techniques for conservative treatment of radiation dermatitis, the most severe cases may require complex surgical reconstruction of the damaged skin, which is why correction and prevention of skin reactions is a priority in patient care. Despite the large number of trials in this area, there are few qualitative comparative studies that can provide a clear picture of the efficacy of individual radiodermatitis-relieving agents. This literature review reviews the current agents used to treat and prevent acute radiation dermatitis, as well as their mechanisms of action. Three electronic databases, including PubMed, Cochrane, and Embase, were used to find information for the systematic review.

Febrile neutropenia is one of the frequent complications of systemic antitumor therapy, characterized by high rates of patient mortality, mortality is particularly high in patients with pre-existing cardiovascular disease, renal disease, as well as in the presence of anemia. In addition, the development of febrile neutropenia is associated with a decrease in the dose intensity of chemotherapy, which also has an adverse effect on the long-term results of treatment of patients with a number of malignant tumors. This dictates the need for widespread use of preventive measures aimed at minimizing the risk of FN in cancer patients receiving cytotoxic chemotherapy. Numerous studies have shown that prophylactic use of granulocyte colony-stimulating factors can significantly reduce the duration of profound neutropenia, the incidence of FN and - most importantly - related mortality. This article is devoted to a review of modern approaches to the use of granulocyte colony-stimulating factors (G-CSF) in the context of the current system of cancer care financing - clinical and statistical groups (CSGs) on the territory of the Russian Federation. Various aspects of the use of drugs of this class to prevent febrile neutropenia in the context of its primary and secondary prevention, the rules of G-CSF use, current data on the effectiveness and feasibility of use in different clinical scenarios are considered in detail. The advantages of modern long-acting dosage forms of G-CSF and their place in modern clinical practice are considered.

Introduction. Melanoma is one of the most deadly human skin tumors, and surgery remains the first and main method in its combined treatment. Despite the seemingly radical nature of surgical interventions in patients with primary skin melanoma, the frequency of locoregional recurrence and metastasis remains high.

Objective. To analyze the effect on the survival rate of the use of plastic methods to close the surgical tissue defect in patients with primary melanoma of the skin after tumor removal in comparison with patients in whom plastic surgery was not used.

Materials and methods. The study used data from 337 patients with stage 0-IIIc primary skin melanoma, randomized into 2 groups: the main group (with the use of plastic closure of a postoperative tissue defect) and the comparison group (with linear suturing of a tissue defect).

Results. It was found that the use of plastic replacement of tissue defect in patients with localized forms of skin melanoma shows the best results of 5-year progression-free survival from 22 to 22.6% (p < 0.050), and at stage 0-IIa and in 5-year corrected overall survival rate up to 13.1% (p < 0.050).

Conclusions. Performing plastic replacement of a tissue defect reduces wound edge tension and rough scarring, accelerates postoperative healing, may be an independent prognostic factor that improves progression-free survival and adjusted overall survival of patients with primary localized skin melanoma, and also be the method of choice among other methods.

Introduction. Fibrolamellar hepatocellular carcinoma (FlC) is a rare subtype of hepatocellular carcinoma (HCC). Drug antitumor treatment of FlC has not been studied sufficiently due to the rarity of the pathology and requires further research to choose an effective treatment.

Aim. The choice of effective drug antitumor treatment in patients with fibrolamellar liver carcinoma.

Materials and methods. The retrospective study included 31 patients with FlC who received drug antitumor therapy at the N.N. Blokhin National Research Center of Oncology of the Ministry of Health of the Russian Federation in the period from 2005 to 2020. The patients were divided into comparison groups: “targeted therapy” (mainly sorafenib), “chemotherapy” (mainly gemcitabine + cisplatin). A comparative intergroup analysis of the effectiveness of drug antitumor treatment in the 1st and 2nd lines of therapy was carried out. Adjuvant chemotherapy was evaluated for time without progression. The correlation of the number of treatment lines in the anamnesis with the prognosis of the disease was also evaluated.

Results. Analysis of the effect of adjuvant therapy on relapse-free survival did not prove significant differences between the comparison groups (p = 0.112; log-rank test). Therapy with multikinase inhibitors (mainly sorafenib) allows to achieve a better time without progression compared to chemotherapy (mainly gemcitabine + cisplatin / oxaliplatin) (p = 0.000; log-rank test) in patients in the 1st line of FlC treatment. OS did not significantly differ between the groups (p = 0.417; log-rank test). In line 2, time without progression in patients receiving targeted therapy (p = 0.042; log-rank test) is higher compared to patients receiving chemotherapy in line 2. A longer duration of OV was recorded in the groups of patients who underwent 2 lines of drug antitumor treatment and in the group of 3 or more lines compared with the use of only 1st line of treatment (p = 0.024) and (p = 0.003), respectively.

Conclusion. The results of the work demonstrate an advantage in the appointment of targeted therapy as the 1st and 2nd lines of drug antitumor treatment, while the appointment of chemotherapy remains a less prognostically favorable option. Adjuvant therapy administration did not demonstrate a statistically significant difference in relapse-free survival.

Biliary cancer is a group of tumors that develop from the epithelium of the intra- and extrahepatic bile ducts (cholangiocarcino-ma), as well as the gallbladder. For 10 years, chemotherapy based on a combination of gemcitabine and cisplatin has remained the standard of first-line therapy in patients with locally advanced or metastatic biliary cancer, resulting in a median overall survival of 11.7 months. With the progression of the disease on the first line, effective options did not previously exist. Attempts to use various chemotherapeutic regimens, both in monotherapy and in combination, have not been successful. In order not to leave the patient without treatment, fluoropyrimidines, their combinations with oxaliplatin or irinotecan, are empirically prescribed as follow-up therapy. In recent years, different subtypes of biliary tract cancer have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma novel therapeutic targets have been identified, including fibroblast growth factor receptor gene fusions 2 (FGFR2) and isocitrate dehydrogenase 1 and 2 mutations (IDH1/2), with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both intrahepatic cholangiocarcinoma and other subtypes of biliary tract cancer, alongside targeting of the immune microenvironment. The growing knowledge of biliary tract cancer biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. In this review, we review recently published data on the use of second-line therapy after progression with standard first-line therapy in patients with biliary cancer.

Mutation or amplification in the PIK3CA gene is one of the most frequent somatic mutations in hormone-dependent Her2neu-negative breast cancer (HR+ Her2neu- breast cancer) and is associated with an increased risk of relapse, progression or death. Understanding the mechanisms leading to hyperactivation of the PI3K-mediated signaling cascade has led to a new class of drugs aimed at inhibiting/suppressing it. Studies of the efficacy of the pan-PI3K inhibitor buparlisib and the beta isoform inhibitor taselisib were formally positive and reached their planned primary sites, but were discontinued due to high levels of toxicity. To date, the only phosphatidylinositol 3-kinase (PI3K) inhibitor approved in clinical practice is alpelsib, which selectively inhibits the alpha isoform of the enzyme's catalytic subunit. The efficacy and safety of alpelisib in combination with fulvestrant for the treatment of postmenopausal women and men with HR+ HER2- PIK3CA-mutated advanced or metastatic breast cancer after prior therapy with aromatase inhibitors was demonstrated in the SOLAR-1 study. The next step proving the efficacy of combination therapy in patients previously treated with endocrine therapy in combination with CDK4/6 inhibitors was the open, multicenter, noncomparative three-arm study BYLieve. The current accumulated clinical experience confirms and complements the findings. In this article, we review clinical cases of the use of alpelisib in patients who previously received hormone therapy, including CDK4/6 inhibitors.

Lung cancer remains the leading cause of cancer-related deaths both in Russia and worldwide, it is often diagnosed at a late stage and the median survival with traditional first-line chemotherapy platinum-based regimens does not exceed one year. The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene offered first opportunity for personalized treatment of advanced non-small cell lung cancer. Currently, molecular testing for patients with advanced-stage lung adenocarcinoma is a routine activity, the use of targeted agents has become the standard of the 1st line of therapy, the treatment strategy after disease progression based not only on the RECIST radiological criteria, but also on the dynamics of clinical symptoms and the identification of a possible mechanism of resistance. The clinical case below demonstrates safe and long-term control of the disease in patient receiving target agents treatment, features of evaluation the effectiveness of the treatment, and also illustrates the advantages of the strategy of continued therapy with asymptomatic progression of the disease.