K.V. Menshikov1,2, A.V. Sultanbaev1, Sh.I. Musin1, I.R. Rakhmatullina2, I.A. Menshikova2, L.A. Khammatova3, E.V. Popova1, N.I. Sultanbaeva1, D.O. Lipatov2

1Republican Clinical Oncology Dispensary, Ufa

2Bashkir State Medical University, Ufa

3Children’s City Polyclinic №9, Kazan

Menshikov Konstantin V. ― Cand. of Sci. (Med.), Associate Professor of the Department of Oncology with courses on oncology and pathological anatomy of IAPE of the Bashkir State Medical University; oncologist of the Department of Chemotherapy of the Republican Clinical Oncology Dispensary

73/1 Oktyabrya Ave., Ufa, 450054, Russian Federation, tel. +7-917-348-82-51, e-mail: kmenshikov80@bk.ru, ORCID ID: 0000-0003-3734-2779

Abstract. According to GLOBOCAN, in 2018 there were about 18.1 million new cases of cancer and 9.6 million deaths from malignant neoplasms. Renal cell carcinoma is the third urologic cancer, accounting for 3% of all cancers in women and 5% in men with an incidence of about 400,000 cases worldwide. Clear cell RCC accounts for the vast majority of RCCs (about 75%). Treatment strategies for metastatic RCC (mRCC) have changed radically over the past 20 years. Initially, first-generation immunotherapy with cytokines: interleukins or interferons were standard approaches, but with poor results. The development of tyrosine kinase inhibitors, mainly vascular endothelial growth factor (VEGF) receptor inhibitors, has greatly improved progression-free survival and overall survival. The emergence of immune checkpoint inhibitors both alone and in combination (anti-CTLA4 and anti-PD-1) has shown interesting results. Immunotherapy is an alternative to anti-angiogenic drugs because clear cell mRCC is considered an immunogenic tumor with a large number of immune cells, such as tumor-infiltrating lymphocytes. The development of new immuno-oncological therapeutics has changed the paradigm for the treatment of patients with mRCC and has changed the role of previous approaches involving anti-angiogenic agents targeting vascular endothelial growth factor (VEGF). Therapeutic options for patients with mRCC have expanded rapidly over the past decade. Targeted immunotherapy is a new cornerstone. Several new drugs are designed to enhance the antitumor immune response and are being studied in ongoing research.

Key words: metastatic renal cell carcinoma, first-line therapy, targeted therapy, tyrosine kinase inhibitors, checkpoint inhibitors, ipilimumab, nivolumab. pembrolizumab, avelumab.