Clinical Review on the Management of Metastatic Renal Cell Carcinoma

Abstract

Renal cell carcinomas vary considerably in their tumor biology and disease course, which is reflected in the range of treatment paradigms in localized and metastatic renal cell carcinoma (mRCC). Active surveillance remains an important component of all renal cell carcinoma management. In mRCC, the rapid evolution from cytokine-based therapy to targeted therapy to immunotherapy with checkpoint blockade has revolutionized the field and drastically altered treatment outcomes. More recently, combination therapies have become a standard of care for most patients with mRCC. In this review, we highlight recent critical data that led to changes in treatment paradigms and provide a practical framework for the management of patients with mRCC.

Activity of ALK Inhibitors in Renal Cancer with ALK Alterations: A Systematic Review

“…Firstly, all ALK-RCC patients treated with ALK-i achieved a radiological response associated with improved performance status, although they all received previous systemic therapies [ 10 , 11 , 12 ]. Considering that most of the anticancer agents used today for the treatment of metastatic RCC are either targeted therapies directed at molecules involved in angiogenesis or ICI [ 49 ], promising results in terms of activity for ALK-i could open the way to a new class of anticancer agents for the treatment of patients affected by metastatic RCC. Four patients were treated with alectinib [ 10 , 12 ], a second-generation ALK-i, while only one patient received crizotinib [ 11 ].…”

“…In the last two decades, the therapeutic scenario of metastatic RCC has been revolutionized, as evidenced by the dramatic improvement of the median survival of RCC patients from less than one year in the 1990s to over four years in the most recent trials [ 59 ]. The treatment landscape has evolved from interleukin 2 and interferon-alfa to targeted therapies such as vascular endothelial growth factor receptor inhibitors, mammalian target of rapamycin inhibitors, and ICI [ 49 ]. Nevertheless, a considerable effort is still necessary to transform the evolving knowledge in identifying novel RCC entities into more personalized treatments.…”

Clear cell renal cell carcinoma with stage IV cavoatrial tumour thrombus extension and rapid metastatic reoccurrence postsurgical treatment with review of current treatment strategies

“…The lack of a head-to-head comparison between the three approved treatment regimens and the significant differences in the patient populations of these studies also create a significant clinical challenge in determining the best regimen for patients. However, indirect analysis of data from these trials suggests that VEGF-directed targeted therapy and immune checkpoint inhibitor combination therapy (pembrolizumab and axitinib) are enhanced in terms of overall response, progression-free survival, and overall survival rates, regardless of international metastatic RCC database consortium risk, thus offsetting the chronic toxicity associated with targeted therapies 24 25…”

Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma

“…The extensive integration of immunotherapy has revolutionized cancer treatment, while introducing a heterogeneous class of immune-related adverse events (irAEs) [ 1 ]. Checkpoint inhibitors (CPI) have routinely been used in the treatment of metastatic renal cell carcinoma (mRCC) since 2015, first as a monotherapy in subsequent lines and currently in the first-line setting as part of combination therapy with either a vascular endothelial growth factor inhibitor (VEGFi) or a second CPI (nivolumab with ipilimumab) [ 2 ]. The risk stratification model for mRCC patients in the VEGFi era, presented by Heng et al, stratified patients according to overall survival (OS) [ 3 , 4 ].…”

“…The model divided patients into favorable-, intermediate- and poor-risk groups according to six prognostic factors. This clinical model has been used for risk stratification in all recent immunotherapy phase III trials [ 2 ] and predicted the superiority of immunotherapy combinations versus sunitinib in intermediate–poor-risk patients. Other biomarkers to predict responses to CPI are still under research.…”