Oligometastatic disease is a term that describes the state of a tumor between a localized tumor and a disseminated process, when all detected tumor lesions are accessible to local action. The concept of oligometastatic disease in advanced cutaneous melanoma has existed since the 1970–1980s, and the role of metastasectomy of solitary lesion is approved in the treatment strategy for this disease. However, the role of local methods before the introduction of modern systemic therapy was quite modest due to the aggressive and often primary disseminated course of the disease. The introduction of immunotherapy and modern targeted therapy in the treatment of metastatic melanoma has significantly increased the number of patients meeting the criteria for oligometastatic disease with the possibility of metastasectomy. Currently, there is no clear algorithm or specific sequence for combining systemic treatment methods with surgical and other local methods. Conditional neoadjuvant immunotherapy is being actively discussed even for primary resectable melanoma metastases; this concept is based on the higher effectiveness of immunotherapy in the presence of tumor tissue in the body and already has practical confirmation from recent studies. In determining the tactics for oligometastatic melanoma, a multidisciplinary approach is extremely important, including a balanced assessment of possible local surgical options, the use of radiotherapy and mandatory systemic disease control. By successfully applying and combining these approaches, it is possible to achieve outstanding success in controlling the disease in a significant proportion of patients. This review provides an analysis of the main and most important works on systemic and surgical treatment of oligometastatic melanoma.

Introduction. Lung cancer remains the leading cause of cancer-related deaths worldwide. For the first time in 30 years, the randomized clinical studies employing immunochemotherapy showed a significant increase in median overall survival for patients with advanced small cell lung cancer. However, no significant predictors of the immunochemotherapy effectiveness were identified.

Aim. To improve long-term outcomes of treatment of patients with advanced small cell lung cancer through search for predictors of the immunochemotherapy effectiveness.

Materials and methods. A total of 35 patients (11 women and 24 men) with advanced small cell lung cancer who received immunochemotherapy with atezolizumab combined with etoposide and carboplatin as first-line treatment were included in the analysis. The average age for patients was 61 years. At the immunochemotherapy baseline, 10 patients had stage IVA disease, 24 patients had stage IVB disease, and one patient had stage IIIB disease. We retrospectively assessed the prognostic impact on the median progression-free survival and overall survival of such factors as leukocytosis, thrombocytosis, lactate dehydrogenase level, neutrophil to lymphocyte ratio, fibrinogen level, blood type.

Results. Median progression-free survival was 6.2 (95% CI 4.6–7.8) months, median overall survival was 16.0 (95% CI 9.4– 22.6) months. There was an increasing trend in median progression-free survival, but without statistically significant differences in leukocytosis, thrombocytosis, elevated fibrinogen levels and normal lactate dehydrogenase levels at the beginning of therapy. The neutrophil to lymphocyte ratio at the beginning of therapy had a significant impact on median progression-free survival. There was a statistically significant increase in median progression-free survival from 4.5 (95% CI 3.9–5.1) to 6.9 (95% CI 5.6–8.2) months when the neutrophil to lymphocyte ratio was < 3. A significant decrease in median progression-free survival – 5.0 (95% CI 3.5–6.5) months was also observed in patients with blood group B (III) vs 6.2 (95% CI 4.7–7.7) months for patients with a different blood group (p = 0.047). Factors such as leukocytosis, thrombocytosis, fibrinogen level, lactate dehydrogenase level and neutrophil to lymphocyte ratio did not have a significant impact on overall survival. Patients with blood type B (III) showed significantly worse survival: median overall survival was 12.1 (95% CI 9.3–14.9) months in blood group B (III) and was not achieved in patients with other blood groups (p = 0.017).

Conclusion. The significance of the identified predictors of the immunochemotherapy effectiveness in patients with advanced small cell lung cancer should be confirmed with the larger sampling size using a multivariate analysis. The study continues a recruitment of patients.

Introduction. The results of the PACIFIC trial have changed the standards of care for the patients with unresectable stage III nonsmall cell lung cancer (NSCLC). However, many patients in our clinical practice do not meet the inclusion criteria of PACIFIC trial.

Aim. To evaluate the long-term outcomes for this approach in real clinical practice in Russia.

Materials and мethods. This real-world observational retrospective multicenter study analyzed clinical outcomes in 100 patients with unresectable stage III NSCLC after concurrent or sequential chemoradiotherapy (CRT). The overall survival (OS) and progression-free survival (PFS) were evaluated by the Kaplan-Meyer method. Multivariate subgroups analysis was performed as well. The median follow-up time was 22.7 months.

Results. There were 96% patients with ECOG/WHO performance status 0 or 1 in our study. Most of the patients were treated by sequential CRT (76%). Median time of durvalumab start from the end of CRT was 34 days. Patients received durvalumab for a median 10 months. The estimated median progression-free survival (PFS) and overall survival (OS) were 14.3 months (11.8–16.7, 95% CI) and 29 months (18.7–39.2, 95% CI), respectively. The estimated 1-year and 2-year rates for OS and for PFS were 90.4%, 62.8% and 59.1%, 35%, respectively. In multivariate analysis, a smoking history (HR = 0.21 (0.10–0.45; 95% CI) and concurrent CRT (HR = 0.3 (0.12–0.74; 95%CI) were associated with better PFS. The smoking history was significantly associated with a better OS (HR = 0.29 (0.10–0.76; 95% CI)) as well.

Conclusions. There is a difference between the real-world outcomes for patients with unresectable stage III NSCLC in Russia and the PACIFIC trial. Sequential CRT is the most frequent treatment option for locally advanced unresectable NSCLC in Russia, and estimated OS and PFS are shorter than in the PACIFIC clinical trial. A paradigm shift in chemoradiotherapy to the concurrent and personalized approach could change the current situation.

The molecular subtype of breast cancer associated with overexpression of HER2/neu is characterized by more frequent and earlier metastasis to the central nervous system, predetermining an unfavorable prognosis for patients in this category. Patients with secondary brain damage by tumors of any location and histological structure are the most complex group of patients, demonstrating an extremely low level of quality of life, requiring special close monitoring and the development of a personal management algorithm. The development of leptomeningeal lesions doubly complicates the specialist’s task due to the severity of the clinical course and resistance to any therapeutic interventions. The emergence in practice of a new drug a conjugate of the humanized antibody immunoglobulin G1 and the topoisomerase I inhibitor, the exatecan derivative trastuzumab deruxtecan (T-DXd) as an additional therapeutic option is new hope for patients with metastatic breast cancer (mBC), including those with damage to the central nervous system. This article provides an overview of the effectiveness and safety of T-DXd in registration studies, demonstrating the clinical benefit of therapy in a patient with HER2-positive (HER2+) mBC with meningeal involvement in real-world clinical practice.

Introduction. Monotherapy with EGFR tyrosine kinase inhibitors (TKIs) results in a worse prognosis for patients with the exon 21 L858R mutation than for patients with exon 19 Del. Thus, the search for alternative drug strategies that improve treatment outcomes for patients with NSCLC with the L858R mutation is an urgent problem. This article presents preliminary results of a pilot study of the effectiveness of chemotherapy integrated into targeted anti-EGFR therapy for patients with non-small cell lung cancer (NSCLC) with a mutation in exon 21 of the EGFR gene.

Aim. To improve progression-free survival results on first-line therapy in patients with NSCLC with the L858R mutation.

Materials and methods. From 2015 to 2021 23 patients were included in the study with advanced L858R 21 exon mutation NSCLC for the first line of treatment. Patients received TKI therapy for the first 2 months, followed by discontinuation of targeted therapy and receiving 3 courses of paclitaxel and carboplatin. Target therapy was then resumed until disease progression. The follow up period was 36 months.

Results. The objective response rate (ORR) was 59.1%. Median progression-free survival 23 months [95% CI: 16–36]. Four (18.1%) patients developed grade 3-4 toxicity during chemotherapy, and therefore the 3rd course of chemotherapy was canceled in one patient. Due to toxicity during targeted therapy, gefitinib dose was reduced in one patient and the drug was changed from gefitinib to afatinib in the other one patient.

Conclusion. Preliminary results of our study showed that integrating chemotherapy into targeted treatment for this category of patients may become a new worthy option to increase median PFS.

ALK-positive non-small cell lung cancer is an excellent model demonstrating the success of precision medicine. A rare genetic disorder – a rearrangement of the anaplastic large cell lymphoma gene, occurring with a frequency of 5–7%, forms a certain clinical and morphological portrait of the patient. In ALK-positive non-small cell lung cancer, the brain is a frequent target for metastasis. But despite this negative prognosis factor, it is in this cohort of non-small cell lung cancer patients that the achievements of drug antitumor therapy are especially significant – the consistent use of ALK inhibitors of several generations allows to achieve a median overall survival of about 80 months. In the Russian Federation, 4 drugs have been approved for the treatment of ALK-positive non-small cell lung cancer. One of them is a second–generation ALK inhibitor – ceritinib is actively used both in the first line of therapy and after progression on crizotinib. In the ASCEND-4 registration study, the median time to progression on ceritinib was twice as long as on standard polychemotherapy. However, the initial daily dose of the drug 750 mg was associated with severe gastrointestinal and hepatotoxicity. Subsequently, the dose of the drug was reduced to 450 mg, which significantly improved the tolerability of treatment without reducing its effectiveness. The clinical case presented below demonstrates the possibility of modern targeted therapy to provide long-term disease control in metastatic ALK-positive nonsmall cell lung cancer.

The polar division of breast cancer into HER2-positive and HER2-negative subtypes has long remained clinically significance. However, up to 60% of HER2-negative tumors have HER2 receptor expression assessed by immunohistochemistry as 1+ or 2+. In the absence of gene amplification, such tumors are classified as HER2-low. Сlassical anti-HER2 agents have not improved treatment outcomes for these tumors. The development of a new generation antibody-cytostatic conjugate, trastuzumab deruxtecan, targeting the HER2 receptor, is changing diagnostic approaches and clinical practice in the treatment of metastatic HER2-low breast cancer. The results of the phase III DESTINY-Breast04 study of trastuzumab deruxtecan in patients with metastatic breast cancer with low HER2 expression became a real revolution. The median progression-free survival in the cohort of patients receiving trastuzumab deruxtecan was 9.9 months versus 5.1 months in the group of patients receiving standard chemotherapy at the physician’s choice (RR 0.50; 95% CI 0.40–0.63, P = 0.003). An objective response during therapy with trastuzumab deruxtecan was recorded in 52.3% of cases versus 16.3% in the standard treatment group. Therapy with the new drug demonstrated a favorable safety profile and did not reduce the quality of life. In this publication, we present our own experience of treating a patient with metastatic luminal HER2-low breast cancer with trastuzumab deruxtecan. Despite the aggressive course, the number of previous lines of therapy and massive liver damage, the use of trastuzumab deruxtecan made it possible to control the disease for 2 years while maintaining a high quality of life for the patient. Trastuzumab deruxtecan is a new effective treatment option for HER2-low metastatic breast cancer.

Lung cancer is currently a heterogeneous group of diseases, whose heterogeneity is determined not only by its phenotypic, but also by its genetic profile. A special place is occupied by subtypes that have driver mutations. Due to new antitumor agents – small molecule inhibitors – it has become possible to significantly increase patients’ chances of survival. The diagnostic panel most often includes mutations in the EGFR, ALK, ROS1, BRAF genes; somewhat less frequently, genetic changes in MET, KRAS, HER2, NTRK, etc. are determined. This distribution is most likely explained by the availability of appropriate inhibitors. The article provides an overview of different generations of ALK inhibitors known in the Russian Federation, among them the most famous: crizotinib, ceritinib, alectinib and lorlatinib. These drugs are included in the clinical guidelines for the treatment of ALK-positive lung carcinomas of all major oncology societies. The article describes the results of registration studies proving the advantage of ALK inhibitors over standard therapy, including the results of the CROWN study. In this study, the latest generation of ALK inhibitors, lorlatinib, demonstrates superiority over crizotinib, with a 73% reduction in the risk of progression or death and better intracranial response rates. A description of a clinical case of treatment of metastatic lung cancer using the third generation ALK inhibitor lorlatinib is provided. The drug was prescribed in the first line of therapy. The patient’s treatment outcome indicates high efficacy of lorlatinib in the first-line treatment of ALK translocation-positive lung cancer, along with low toxicity. The treatment period has already been more than 70 months and the patient continues therapy at the time of the last control. A complete response to lorlatinib therapy was recorded. During treatment, the following adverse events were recorded: hypertriglyceridemia, grade 1 toxicity, hypercholesterolemia, grade 2 toxicity, increased liver transaminases, grade 1 toxicity.

Cervical cancer is one of the most common malignant tumors in Russia. Despite the high cure rates with local treatment approaches (eg, surgery or radiothearapy) at early stages of the disease, metastatic cervical cancer portends an unfavorable prognosis. The incidence and mortality rates over the last 10 years remain at a consistently high level. The backbone of treatment for metastatic cervical cancer is platinum-based combinations – the cytototic combination of paclitaxel and cisplatin (or carboplatin) being a standard-of-care treatment for patients with metastatic disease. However, chemotherapy alone failed to achieve satisfactory long-term treatment outcomes – the expected life expectancy with chemotherapeutic drugs rarely exceeds 12 months. One of the most fruitful directions in the treatment of metastatic cervical cancer to date is immunotherapy – in particular, pembrolizumab, a PD-1 pathway inhibitor – one of the key checkpoints of the immune response control. This review article highlights historical and recent achievements in metastatic cervical cancer treatment. It highlights the development of anticancer medications for advanced or metastatic cervical cancer, including targeted antiangiogenic therapy, immunotherapy, and the latest research data on the effectiveness of combining these classes of drugs with standard cytotoxic chemotherapy to achieve the best treatment outcomes.

Renal cell carcinoma is one of the most common diseases in oncourology. The leading morphological variation of renal cell carcinoma today is the light-cell subtype, which is determined in 80% of cases. Despite the intensity of diagnostic methods, almost 1/3 of patients with kidney cancer have distant metastases during initial examination, which causes extremely high mortality rates from this oncopathology. Standard chemotherapy schemes with the inclusion of fluoropyrimidines and antitumor antibiotics, cytokine therapy using interleukin-2 and interferon α only slightly prolonged the life of patients, while causing pronounced toxic-anemic adverse events. The appearance of tyrosine kinase inhibitors has allowed us to obtain really significant results in the treatment of metastatic renal cell carcinoma. The next step in the treatment of renal cell carcinoma was the registration by the US FDA in April 2018 of a combination of immuno-oncological drugs ipilimumab and nivolumab for the treatment of metastatic renal cell carcinoma. Afterwards, combinations of immune checkpoint inhibitors with targeted drugs were registered, which not only significantly increased the life expectancy of patients, but also reduced the incidence of adverse events of antitumor therapy. This article provides clinical examples demonstrating the effectiveness of the combination of pembrolizumab and axitinib in the treatment of patients with metastatic renal cell carcinoma.

The prognosis of chronic myeloid leukemia (CML) has changed during the past two decades from a disease with an overall survival of 5 years only to one in which patients can enjoy a near normal life-expectancy. Such remarkable improvement in the patients’ outcome is mainly due to the introduction of imatinib into the clinic (the first approved tyrosine kinase inhibitor [TKI]), but also to the approvals of others TKIs. Currently, there are six TKIs available for CML treatment in clinical practice. The article discusses the effectiveness and safety of only the 2nd generation of ITCs, each of which has its own range of both adverse events and advantages when prescribed in the first or subsequent lines of CML therapy. Although a proportion of patients (around 25%) will be able to successfully discontinue TKI treatment after achieving a deep molecular remission, most of them will require to keep on treatment indefinitely. In such a situation, it is crucial for doctors caring for CML patients to be aware of which TKIs are available for each particular clinical situation, what can be expected from them, and how to manage their potential side effects. In the present review, we will briefly address these issues from a practical point of view.

Among the childhood cancers, neuroblastoma ranks fourth. This tumour is considered the most common extracranial malignant neoplasm in children and was first described in 1865 by the German scientist Rudolf Virchow. Neuroblastoma has the unique ability to undergo increased cell differentiation and transform into ganglioneuroma. In some cases, the disease can be asymptomatic and may undergo spontaneous regression or maturation into a benign tumour. However, neuroblastoma often has an aggressive course with early metastasis. Due to the ambiguity of clinical symptoms, the primary diagnosis of neuroblastoma in children requires pediatricians to be acutely aware of oncological emergencies and initial signs such as increased abdominal size and asymmetry, neurological symptoms, pain, and dysuria. In low-risk patients, minimal therapy, including surgery alone, achieves long-term survival in more than 90% of cases. Achieving similarly high survival rates in the intermediate-risk group is possible only with the use of modern polychemotherapy regimens in combination with surgical treatment and, in some cases, radiation therapy. High-risk patients require a combination of the aforementioned methods together with autologous or allogeneic hematopoietic stem cell transplantation, with long-term overall survival rates not exceeding 50%. The most favorable prognosis is seen in patients with localised disease under the age of one year. This article describes the features of tumour development, the course of the disease, and the evolution of diagnostic and therapeutic strategies from the past to the present.

Anticancer drug therapy has made significant progress in the last two decades. However, the correction of adverse events and complications that arise during treatment requires special attention. Most often, special antitumor therapy can cause side effects from the gastrointestinal tract. Chemo-induced nausea and vomiting is the most common adverse event associated with drug therapy of cancer. It significantly worsens the well-being and quality of life of patients. With multiple cycles of chemotherapy, episodes of both acute and delayed nausea/vomiting may occur. There are several pharmacological groups of antiemetics. The most effective regimen for the prevention of chemotherapy-induced nausea and vomiting is a combination of serotonin receptor (5-HT3) and neurokinin receptor (NK-1) antagonists. It provides high symptom control in both the acute and delayed phases of nausea/vomiting. Palonosetron, a new-generation serotonin receptor antagonist, differs from firstgeneration 5-HT3 receptor antagonists in its stronger and longer-lasting antiemetic effect with a comparable safety profile. Oral administration of palonosetron is not inferior in effectiveness to its intravenous administration. An oral combination drug containing the NK-1 antagonist netupitant and the 5-HT3 antagonist palonosetron is highly effective in preventing nausea and vomiting in moderately and highly emetogenic drug regimens. The long half-life of both drugs and their high affinity to their receptors provide a long-lasting and persistent effect even with a single dose. This combination is particularly effective in relieving symptoms of delayed nausea/vomiting. A number of clinical studies have demonstrated that a single oral dose of netupitant/palonosetron combination is significantly more effective than 3-day aprepitant-based regimens in preventing delayed chemotherapy-induced nausea and vomiting. In addition, the netupitant/palonosetron combination may be cost-effective by reducing the cost of managing of complications of poorly controlled nausea and vomiting.

In the middle of the last century, the discovery of a number of cytotoxic agents was an incredible achievement in the treatment of malignant tumors. However, their use was limited by adverse events, primarily the development of myelosuppression. The occurrence of neutropenia is associated with frequent and extremely dangerous events that do not allow timely initiation of a new cycle of therapy and increases risk of infectious complications. Over the years, many attempts have been made to develop optimal management tactics for patients receiving cytotoxic therapy, including antibiotic therapy, the use of nonspecific myelopoiesis modulators, and even blood transfusions. With the advent of granulocyte precursor maturation stimulators in 1983, the situation has improved greatly. Filgrastim and its bioanalogues, registered later, made it possible to reconsider approaches to the use of intensified chemotherapy regimens. It has become possible to control the incidence of neutropenia using only subcutaneous forms of granulocyte colony-stimulating factors (GCSF). The article presents a clinical observation of the use of filgrastim in neoadjuvant therapy of early breast cancer. Filgrastim not only helped to cope with the development of newly diagnosed febrile neutropenia, but during continued treatment it prevented the development of adverse events. The administration of GCSF allowed timely completion of treatment with a complete pathological response, providing the patient with better survival prognosis.

Introduction. Although immuneand targeted therapy have become successful in recent years, platinum-based chemotherapy continues to have a place in the up-front treatment for metastatic non-small cell lung cancer (NSCLC).

Aim. Tо evaluate the overall survival (OS) of patients with metastatic NSCLC who were treated with immune checkpoint inhibitors either as first-line or second-line treatment in clinical practice in Russia.

Materials and methods. Using real-world database, we retrospectively selected 232 patients with metastatic NSCLC without driving mutations. Of these patients, 82 received chemoimmunotherapy as the initial treatment (group 1) and 150 patients were treated with platinum–based chemotherapy followed by immunotherapy as the second line (group 2). Multivariate subgroup analyses were performed. The median time from the start of treatment to data cut off was 38.4 months.

Results. The median OS was the same in the first and second group, 21.0 months (14.4–27.6; 95% CI) and 22.4 months (17.6–27.19; 95% CI); estimated 3-year OS was 40% and 36.6%, respectively. The hazard ratio (HR) for patients in the immunochemotherapy group was 1.02 (0.72–1.44; 95% CI) compared with patients who received second-line immunotherapy. In multivariate analysis, non-compliance with basic inclusion criteria in clinical trials (ECOG 2–3, serious intercurrent illness, active infection, chronic infection, corticosteroids need) (HR = 1.71 (1.21–2.4; 95% CI), the liver metastasis (HR = 1.76 (1.09–2.84; 95% CI) and gender (male vs. female HR = 1.68 (1.04–2.71; 95% DI) were significantly associated with the shorter OS.

Conclusions. The overall survival in patients who received immunotherapy in the second line of treatment did not differ from the results of treatment for the patients after immuno-chemotherapy in the first line. The crucial is the receiving of immunotherapy regardless of the line. Failure to meet the criteria of inclusion in clinical trials significantly worsens the long-term outcomes.

Introduction. An increase in the life expectancy of patients with HCC can be achieved both by improving treatment methods and by implementing early examination through screening programs.

Aim. Evaluation of the impact of screening in risk groups on early detection of HCC, on the possibility of specialized treatment, on one-year overall survival of patients with HCC.

Materials and methods. The clinical records of 148 patients with HCC and liver cirrhosis (LC) who received medical care at the Sverdlovsk Regional Oncology Center in 2022 with the follow-up period exceeding 12 months were retrospectively studied. HCC was diagnosed as a result of screening carried out on the basis of the Regional Hepatological Center in 34 patients. 114 patients were referred to the oncological hospital due to the detection of a malignant tumor in liver during examination in cause of complaints. The compared groups of patients did not differ in age and sex composition, in the frequency of smoking, alcohol consumption, drug addiction, viral hepatitis B, obesity, diabetes mellitus, arterial hypertension, oncological heredity, in the distribution of LC by class. Patients with HCC detected at screening had a better general somatic status (p < 0.001), more often had viral hepatitis C (82.4% vs. 35.1%, p < 0.001) and AFP above normal (64.7% vs. 43.0%, p = 0.027).

Results. Screening influenced the staging of newly diagnosed patients with HCC. If the proportion of stages B and C according to the Barcelona system remained the same, then stage A accounted for 32.4% versus 12.3% (OR = 3.42; 95% CI 1.37–8.49; p = 0.007). Stage D, on the contrary, was less: 8.8% vs. 36.8% (OR = 0.17; 95% CI 0.05–0.58; p = 0.002). Identification at earlier stages and better general condition of patients influenced the possibilities and results of treatment. In the HCC group after screening more patients received treatment: 88.2% versus 56.1% (OR = 5.86; 95% CI 1.94–17.73; p < 0.001). There was a higher one-year overall survival: 79.4% vs 39.5% (OR = 5.91; 95% CI 2.38–14.73; p < 0.001).

Conclusion. Screening for HCC in risk groups improves early diagnosis, increases the likelihood of patients receiving specialized anticancer treatment and increases the one-year overall survival rate.

Gastric cancer (GC) is one of the most aggressive and unfavorably ongoing malignant neoplasms, occupying the fifth and fourth places in the structure of oncological morbidity and mortality, respectively. Overexpression of the human epidermal growth factor receptor 2 (HER2-neu) is detected in about 20% of patients with advanced GC, which made it possible to successfully use trastuzumab in combination with chemotherapy (CT) in this cohort of patients. The development of resistance to trastuzumab is a serious problem that requires research and development of new therapy targeted to blockHER2-neu. Trastuzumab deruxtecan is an antibody–drug conjugate consisting of an antibody to the HER2-neu receptor and a topoisomerase inhibitor linked by a cleavable tetrapeptide-based linker. The drug has proven its effectiveness as a monotherapy for the treatment of patients with metastatic or locally advanced HER2-positive gastric adenocarcinoma or cardio esophageal junction in the 2nd and subsequent lines of treatment. In the above clinical case a 57-year-old patient with CEС adenocarcinoma with metastatic liver damage, distant lymphnodes and the presence of HER2-neu overexpression is presented. After the standard first-line drug treatment according to the XELOX scheme with trastuzumab, the patient underwent surgical treatment followed by postoperative chemotherapy according to the FOLFOX scheme in combination with trastuzumab. Given the negative dynamics, the next step was 3 injections of nivolumab immunotherapy, which eventually led to the development of autoimmune hepatitis and rapid progression of the disease. Almost the last hope for the patient was the introduction of trastuzumab deruxtecan, which allowed for an objective response, as well as an improvement in the patient’s clinical condition, which led to the achievement of the longest possible progression-free survival (PFS).

In recent years, the active search and development of new therapeutic agents for a prognostically unfavourable group of patients with disseminated non-small cell lung cancer (NSCLC) has continued. Studies show that the occurrence of lung cancer can be associated with mutations of driver genes such as EGFR, ALK, ROS1, BRAF, KRAS, RET, MET, HER2, NTRK1/2/3, etc., in the normal processes of growth, proliferation, differentiation. The discovery of targeting drugs with high activity against certain mutations has led to a paradigm opening of therapeutic approaches and continued prognosis in serious disease. The presence of activating mutations predetermines the clinical and morphological profile of the patient. One of the random mutations – MET mutation with exon 14 skipping (METex14) is observed, as a rule, in patients of older age group, with disseminated tumour process, more aggressive course of the disease and poor prognosis with chemotherapy alone. This case provides an opportunity for long-term disease control while maintaining satisfactory quality of life in an elderly patient with NSCLC associated with METex14 mutations, as well as providing a major role and method for obtaining next-generation value for personalisation of therapy and new insights into the scientific targets and the future use of molecules to them.

Fibrolamellar hepatocellular carcinoma is a rare primary liver tumor with no known risk factors, which occurs in 1–7% of cases of all hepatocellular carcinoma. The disease occurs mainly in adolescents, as an accidental finding or when symptoms appear already during the metastatic process. The main method of treatment with proven efficacy for localized fibrolamellar hepatocellular carcinoma is surgical. The experience of using radiation therapy and transarterial chemoembolization is contradictory and needs additional study. The option of preferred drug antitumor treatment is not fully clear, and the search for effective therapy regimens and potential targets specific to this form of hepatocellular carcinoma is relevant and requires further study. Considering the rarity of the pathology, the world literature presents data on the treatment of small groups of patients and clinical cases of successful use of a number of medicinal antitumor regimens. However, the data are contradictory. The literature describes isolated clinical cases of successful use of immunotherapy in patients with fibrolamellar hepatocellular carcinoma, requiring further detailed study. Using the example of this clinical case, we have shown the successful long-term use of combined immunotherapy in a patient with fibrolamellar liver carcinoma.