Treatment of NCCRCC after the progression of first line therapy remains an important challenge. This group of cancer is very heterogeneous with different biological behaviors, which makes it difficult to achieve a one-size approach. Although survival rates and the tripling of the response-large progress were made in the frontline therapy, the options for patients who go beyond the first line treatments are limited. Historically speaking, second therapies mainly consisted of VEGF Tyrosinkinase inhibitors of individual agents (TKI), which showed a modest activity with the response rates of around 10 to 15%. This lack of highly effective options contributes to the complexity of the treatment of refractory diseases.
In current practice, patients who have not previously received IO are usually taken into account for IO-based combinations after the progression. Although sometimes outside the label, the combination of immunotherapy with TKIS seems to offer better results than individual active ingredients, which indicates a synergistic benefit. Data from certain studies also support this approach with remarkable response rates in the second attitude. For certain subtypes such as chromophobic -rcc, MTOR inhibitors have promising, with some patients with longer reactions. In addition, Lenvatinib in combination with Everolimus is treatment for this subtype, especially if they are not used beforehand. Optimizing treatment based on the patient's cancer biology and previous therapies is the crucial way to treat progressive diseases.
Despite these strategies, the NCCRCC field has the evidence-based treatment options faster compared to Clear Cell RCC. This scarcity underlines the crucial importance of writing down patients into clinical studies, including early phase studies, to examine new therapies and improve the results. Further research and real evidence are important in order to guide treatment decisions and to expand the therapeutic landscape for this challenging and diverse group of kidney cancer.