Onkológia 6/2020

Optimal first line treatment in advanced/metastatic renal carcinoma-immunotherapy, targeted therapy, combinations

Renal cell carcinoma (RCC) accounts for 3 % of all malignancies, represents the 7th most common cancer in men and the 10th most common cancer in women. RCC is very heterogenic disease, presented with approximately 80 % of clear cell carcinomas and 20 % of non-clear cell RCC, most in them represented with papillary and chromophobe carcinomas. Sarcomatoid dedifferentiation can arise in any histologic subtype or stage of disease and relates to a rapid progression and high mortality rate. Approximately 25% of patients with RCC are initially diagnosed in metastatic stage of disease, while the rest of patients in localized stage, but 20-40 % out of them will progress during their disease. Localized RCC is primary solved by surgery, ablation or in selected cases by observation, as well. In advanced or metastatic disease, the main therapeutic modality is systemic treatment followed by cytoreductive nephrectomy (CN) in most of the cases. In the center of treatment of RCC, today and in the past, as well, was immunotherapy and targeted therapy, in the fact that responses to the cytostatic or radiotherapy were low. Until 2006 the only treatment modality was cytokine immunotherapy, interleukin-2 (IL-2) and interferon- α (IFN- α), followed by biologic therapy with tyrosine-kinase inhibitors in monotherapy with limited effectivity. Gradually, other agens were incorporated into the treatment of RCC, like potent multi-kinase inhibitors or newly discovered checkpoint inhibitors, that dramatically changed the treatment landscape as well as prognosis of RCC. Checkpoint inhibitors targeting pathways of programmed death protein (PD-1), ligand of programmed death protein 1 (PD-L1) and with cytotoxic T-lymphocyte associated protein - 4 (CTLA-4) became integral part of the treatment of RCC. These checkpoint inhibitors became new standard in treatment of advanced RCC in monotherapy first and afterwards in first line combinations with VEGF-inhibitors.

Keywords: advanced/metastatic renal cell carcinoma, immunotherapy, targeted therapy, first line options