The Current State of Immune Checkpoint Inhibitors in the First-Line Treatment of Renal Cancer

Abstract

Until recently, tyrosine kinase inhibitors (TKI) were the only approved drugs for the first-line treatment of metastatic renal cell carcinoma (mRCC). Emerging trials of immune checkpoint inhibitors (ICI)-based regimens have shown survival benefits over the standard TKI. These studies challenge a paradigm shift in the management of mRCC concerning the identification of the subgroup of patients that would benefit from ICI in treatment-naive mRCC, the possibility of treatment discontinuation between TKI and ICI, and the sequencing of surgery and systemic treatment. This paper reviews the currently available data and discusses the paradigm shift concerning first-line treatments of mRCC.

Immunotherapy failure in adrenocortical cancer: where next?

“…Basic science uncovered the pathways restraining antitumor immunity and drugs targeting immune checkpoint molecules, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), are important therapeutic breakthroughs in medical oncology ( 5 ). These drugs have demonstrated to be efficacious (and obtained the US Food and Drug Administration – FDA – approval) against a broad spectrum of cancer types including metastatic melanoma, non-small-cell lung cancer, renal cell carcinoma and urothelial cancer ( 6 , 7 , 8 , 9 ).…”

Tyrosine kinase inhibitors and immunotherapy combinations in renal cell carcinoma

“…7 Currently, there are two major types of combination regimens approved in mRCC including a combination of two ICI and combinations of antiangiogenic therapy and an ICI. 61,62 The combinations of nivolumab plus ipilimumab has become a standard of care in mRCC following the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approval for patients with intermediate and poor-risk disease. 7,61 Positive outcomes for the ICI and TKI combination are now validated in large phase III randomized trials leading to FDA and EMA approval in unselected treatment-naïve patients for pembrolizumab plus axitinib and avelumab plus axitinib.…”

Interleukin 17 and Its Involvement in Renal Cell Carcinoma

“…Importantly, the management of mRCC requires a multidisciplinary approach and aiming the optimal treatment strategy to patients with RCC [ 72 ]. Formerly, tyrosine kinase inhibitors (TKI) were the only drugs for the first-line treatment of metastatic renal cell carcinoma (mRCC) [ 73 ]. Recently approved immune checkpoint inhibitors (such as PD-1-blocker nivolumab) have changed the standard of metastatic kidney tumor therapy and the use of immune checkpoint inhibitors in mRCC presents a new age of treatment of this disease [ 63 , 73 ].…”