Abstract
The incidence of renal cell carcinoma (RCC) is rising and metastatic RCC carries a very poor prognosis. The treatment paradigm for metastatic RCC has shifted dramatically in the last decade with multi-targeted tyrosine kinase inhibitors (TKI) previously used as first-line treatment but its utility is limited by short-lived efficacy and rapid disease progression. The dysregulation of immune cells in the tumour microenvironment contributes to unregulated growth of RCC. Thus, the use of immune checkpoint inhibitors has become first-line treatment for metastatic RCC and has offered dramatic improvement in clinical benefit and survival. Treatment with immune checkpoint inhibitor in combination with TKI appears to be promising in offering even greater response rates. The treatment for metastatic RCC continues to evolve and ongoing advances with new targeted agents and biomarkers are needed to continue to improve prognosis in the future.
Highlights
Renal cell carcinoma (RCC) has an incidence of approximately 400,000 cases per year globally, which is highest in North America, Europe and Australia [1]
In the phase III trial, CheckMate-025, nivolumab used in a second-line treatment setting, demonstrated a higher objective response rate of 25% compared to 5% in everolimus and a significant increase in overall survival of 25 months compared to 19.6 months in the everolimus group [25]
The most recent European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) guidelines recommend enrolment of patients with non-clear cell RCC (nccRCC) onto clinical trials if possible. Targeted therapy such as anti-vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) are recommended as first-line treatment of papillary, chromophobe, translocation and unclassified nccRCC whereas platinum-based chemotherapy is recommended for treatment of medullary and collecting duct RCC [29, 30]
Summary
Renal cell carcinoma (RCC) has an incidence of approximately 400,000 cases per year globally, which is highest in North America, Europe and Australia [1]. The use of immune checkpoint inhibitors nivolumab and ipilimumab is approved for first-line treatment of intermediate and poor-risk metastatic RCC and has demonstrated improved overall survival across multiple clinical trials (Table 1). In the phase III trial, CheckMate-025, nivolumab used in a second-line treatment setting, demonstrated a higher objective response rate of 25% compared to 5% in everolimus and a significant increase in overall survival of 25 months compared to 19.6 months in the everolimus group [25]. In the pivotal phase III trial CheckMate-214, treatment with nivolumab and ipilimumab in the first-line setting for metastatic ccRCC resulted in a higher response rate (42% vs 27%, p
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