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The optimal hepatocellular cancer (HCC) therapy remains a challenge. Due to checkpoint inhibitors patients with intolerance to the targeted therapy and or those with the impaired liver function can get an appropriate drug therapy. This clinical observation illustrates the long-term effect of pembrolizumab as the 2-line therapy in a patient diagnosed with. Sorafenib in standard doses as first line therapy led to severe toxicity and necessitated the withdrawal of therapy. Although subsequently the doses were reduced and concomitant medications used, sorafenib therapy was discontinued due to pronounced side effects typical of kinase inhibitors. From August 2017 to September 2019, as a part of a clinical study, the patient received 35 courses of immunotherapy with pembrolizumab 200 mg i.v. every 3 weeks, with satisfactory tolerance. The best response - partial tumor regression – was achieved at 84 weeks of therapy and continues to this day. Favorable toxicity profile makes checkpoints inhibitors a good treatment option in patients with impaired liver function (Child-Pugh 7–8 points) or with intolerable toxicity of kinase inhibitors.

Introduction. Lung cancer remains the one of the most common and fatal cancers in the world. For a long time, chemotherapy was the only treatment option for metastatic lung cancer. Currently, immunotherapy became the one of the preferred options of treatment.The purpose of our work was to evaluate the long-term results of using the PD-1 inhibitor nivolumab in real-world settings.Materials and methods. 108 pretreated patients with metastatic NSCLC were included in this non-randomized, observational study. The median follow-up time was 54.5 months.Results. Median overall survival was 8.8 months (6-12, 95% CI). The five-year overall survival rate was 19.4%. Median progressionfree survival was 3.9 months (3-5, 95% CI). The five-year progression-free survival rate was 7.7%. Overall response rate (ORR) was 18%. In patients with ORR, the median overall survival was not achieved. Prolongation of immunotherapy after disease progression had a positive effect on the overall survival of patients. Clinically significant immuno-related adverse events developed in 21% of patients, but only 7.3% showed the development of adverse events grade 3-4 that required discontinuation of immunotherapy. A rare complication that we met was a case of encephalopathy, to which the patient achieved durable complete response despite discontinuation of immonotherapy.Conclusion. Received survival, efficacy and safety data may inform treatment decisions for patients with metastatic NSCLC in real world settings.

Recently immune checkpoint inhibitors amazingly changed the landscape of cancer therapy worldwide. The number of immune checkpoint molecules in clinical practice is constantly increasing. There are some monoclonal antibodies recently registered in the Russian Federation: anti-PD1 antibodies (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab), anti-CTLA-4 (ipilimumab). Immune-mediated endocrinopathies are some of the most common complications of immunotherapy. According to the results of clinical studies, the incidence of serious endocrine immuno-mediated adverse events with anti-PD1 monoclonal antibodies is low (3.5–8%). The use of anti-CTLA4 antibodies, combined regimens, and the use of immunotherapy after chemoradiotherapy significantly increase the incidence of serious adverse events to 30%. In clinical practice of N.N. Blokhin Cancer Research Center among 245 non-small cell lung cancer and hepatocellular carcinoma patients treated with immunotherapy, 22 (8,9%) developed an immune-mediated endocrinopathy. Most patients developed adverse events of 1–2 degrees, in two patients – 3 degrees, requiring discontinuation of treatment. The aim of this article was to provide useful information and recommendations regarding the management of common immuno-related endocrine adverse events (including hypothyroidism, hyperthyroidism, pituitary, adrenal insufficiency) for clinical oncologists.