Abstract
PurposeCurrent systemic treatment of targeted therapies, namely the vascular endothelial growth factor-antibody (VEGF-AB), VEGF receptor tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitors, have improved progression-free survival and replaced non-specific immunotherapy with cytokines in metastatic renal cell carcinoma (mRCC).MethodsA panel of experts convened to review currently available phase 3 data for mRCC treatment of approved agents, in addition to available EAU guideline data for a collaborative review as the plurality of substances offers different options of first-, second- and third-line treatment with potential sequencing.ResultsSunitinib and pazopanib are approved treatments in first-line therapy for patients with favorable- or intermediate-risk clear cell RCC (ccRCC). Temsirolimus has proven benefit over interferon-alfa (IFN-α) in patients with non-clear cell RCC (non-ccRCC). In the second-line treatment TKIs or mTOR inhibitors are treatment choices. Therapy options after TKI failure consist of everolimus and axitinib. Available third-line options consist of everolimus and sorafenib. Recently, nivolumab, a programmed death-1 (PD1) checkpoint inhibitor, improved overall survival benefit compared to everolimus after failure of one or two VEGFR-targeted therapies, which is likely to become the first established checkpoint inhibitor in mRCC. Data for the sequencing of agents remain limited.ConclusionsDespite the high level of evidence for first and second-line treatment in mRCC, data for third-line therapy are limited. Possible sequences include TKI-mTOR-TKI or TKI–TKI-mTOR with the upcoming checkpoint inhibitors in perspective, which might settle a new standard of care after previous TKI therapy.
Highlights
Kidney cancer accounts for about 2–3 % of all cancers in the world each year and is the third-most common urological tumor
The optimal therapy for patients with clear cell renal cell carcinoma (RCC) (ccRCC) is generally chosen after the stratification according to the MSKCC (Memorial Sloan-Kettering Cancer Center) or IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) criteria [12, 13]
For patients with an unfavorable prognosis, temsirolimus showed a survival benefit when compared to IFN-α; this mammalian target of rapamycin (mTOR) inhibitor is regarded as a standard for this subgroup of patients [1, 14]
Summary
Kidney cancer accounts for about 2–3 % of all cancers in the world each year and is the third-most common urological tumor. The most common type of renal tumors in adults is renal cell carcinoma (RCC), which represents approximately 90–95 % of all cases [1, 2]. RCC includes different entities, with the most common histological subtype being clear cell (ccRCC) of about 75–80 % (Fig. 1). All other subtypes are summarized as nonclear cell RCC, which include papillary (papRCC), chromophobe RCC (chRCC) and various other entities [3]. The different subtypes are characterized by their distinct molecular patterns, which reflect pathway alterations leading to the tumor growth. These alterations arise from inherited genetic disorders, which underlie a specific syndrome, or more often from sporadic non-hereditary mutations [4, 5]
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