K.V. Menshikov1,2, A.V. Sultanbaev1, Sh.I. Musin1, A.A. Izmailov1,2, 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:, ORCID ID: 0000-0003-3734-2779

Abstract. In 2018, there were about 18.1 million new cancers and 9.6 million cancer deaths worldwide, according to GLOBOCAN. Renal cell carcinoma is one of the ten most commonly diagnosed cancers in the world. One of the most common types of renal cell carcinoma is clear cell carcinoma, which accounts for about 75% of all malignant neoplasms. More rare types are tumors such as: papillary or chromophilic type occurs in 10-15%, develops due to changes in the structure of cells that line the pelvis, diagnosed relatively rarely, amenable to treatment, has a relatively favorable prognosis; Collecting duct cancer (Bellini) in the medulla of the kidney, diagnosed in less than 1% of cases with a poor prognosis due to resistance to treatment; chromophobic ― develops in 4-5% of the cortical part of the collecting tubules of the kidney; oncocytic kidney cancer.

Approximately 25% of patients with an established diagnosis of RCC have metastatic disease at the time of diagnosis and require systemic treatment. Moreover, an additional 20-50% of RCC patients with localized disease develop metastatic RCC (mRCC) over time.

Inhibitors of tyrosine kinases have become firmly established in oncological practice and are currently used in many oncological diseases. The second line of therapy for metastatic renal cell carcinoma currently remains a rather controversial issue. From 2006 to 2017, VEGF-targeted therapy was the standard of care in the forefront. Commonly used second-line drugs include axitinib, a tyrosine kinase inhibitor of selective VEGF receptors (VEGFR), and an mTOR inhibitor, everolimus. Since 2015, three new second-line options for the treatment of metastatic renal cell carcinoma have become available ― nivolumab, a checkpoint inhibitor; cabozantinib, a tyrosine kinase inhibitor; and a combination of the tyrosine kinase inhibitor lenvatinib with everolimus. Ongoing studies of combinations of tyrosine kinase inhibitors and control inhibitors, including those with axitinib, cabozantinib, and lenvatinib, have demonstrated clinical efficacy and acceptable toxicity. As therapeutic options continue to evolve, there is a need to better understand the mechanism of resistance to targeted drugs, checkpoint inhibitors, and combinations thereof. Prognostic biomarkers need to be investigated. More data is also needed to assist clinicians in routine practice, which is, of course, different from clinical trials, where patients are carefully selected.

Key words: metastatic renal cell carcinoma, second line, targeted therapy, tyrosine kinase inhibitors, checkpoint inhibitors, axitinib, cabozantinib, everolimus, nivolumab, lenvatinib, VEGF, mTOR.