The Immunotherapy Landscape in Renal Cell Carcinoma
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REVIEW ARTICLE
The Immunotherapy Landscape in Renal Cell Carcinoma Landon C. Brown1,2 · Kunal Desai3 · Tian Zhang1,2 · Moshe C. Ornstein4,5
© Springer Nature Switzerland AG 2020
Abstract The past 30 years have borne witness to a gradual evolution in the treatment landscape of advanced renal cell carcinoma (aRCC). Early immunotherapy approaches such as interferon-α and high-dose interleukin-2 (IL-2) therapy in this immunogenic tumor provided durable responses in only a minority of patients and came with toxic side effects. A growing understanding of the tumor biology elucidated pathways of tumorigenesis, which in turn revealed novel targets amenable to targeted therapies. Inhibition of angiogenesis and cell signaling emerged as cornerstones of treatment with the approval of bevacizumab and several pan-kinase and tyrosine kinase inhibitors. Though effective, their use has been limited by low rates of durable response, resistance, and side effects. The immunotherapy revolution of the past decade has led to immunotherapybased combination regimens such as ipilimumab plus nivolumab, pembrolizumab plus axitinib, and avelumab plus axitinib, displacing single agent anti-angiogenic therapy in the first-line setting by demonstrating durable responses and improved survival over sunitinib. These immunotherapy-based combinations define first-line standard of care for aRCC today. The pipeline of second-line agents for consideration in patients who have disease progression despite immunotherapy regimens is robust but still in early stages of development. Key Points The therapeutic landscape of advanced renal cell carcinoma (RCC) has changed significantly in the past 3 decades. Insights into the tumor biology of RCC have yielded novel targets that informed targeted approaches such as inhibition of angiogenesis, cell signaling, and anti-tumor immune response. Newer immunotherapy combinations have largely displaced targeted therapies in the first-line setting.
1 Introduction Renal cell carcinoma (RCC) comprises a heterogeneous set of cancers that includes 16 tumor subtypes defined by various genotypes and histopathology. Whereas the 5-year survival rate across all stages has improved from 52 to 75% in the past 3 decades, only 12% of patients with metastatic disease are alive after 5 years [1]. The therapeutic armamentarium has evolved considerably over that time to include targeted therapies and immune checkpoint inhibitors (Table 1). In this review we will discuss the current state of immunotherapy-based treatments and biomarkers for advanced (aRCC) or metastatic RCC (mRCC) as well as promising investigational approaches.
Landon C. Brown and Kunal Desai: Co-first authors. * Moshe C. Ornstein [email protected] Landon C. Brown [email protected] Kunal Desai [email protected] Tian Zhang [email protected] 1
Division of Medical Oncology, Department of Medicine, Duke University, DUMC 103861, Durham, NC 27710, USA
2
Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA
3
Department of In
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