Antiangiogenic therapies remain the standard of care in the front-line setting for renal cell carcinoma, although vascular endothelial growth factor (VEGF) blockade is not sufficient, and many patients do not respond to such treatment. With a host of approved agents, questions arise as to how best to use them in both initial and secondary treatments. Optimal sequences are currently being tested in various clinical trials. Because approximately 20% of patients exhibiting primary resistance to these anti-VEGF therapies, new therapies are needed. Novel therapies such as MET and AXL inhibitors as well as checkpoint antibodies hold promise for the future.
In 2017, pazopanib and sunitinib remain the mainstays of frontline therapy for advanced renal cell carcinoma. Independent review of frontline cabozantinib therapy may alter standard of care for patients at intermediate and poor risk. Multiple agents show a survival advantage in the second-line setting, including nivolumab, cabozantinib, and combination lenvatinib and everolimus. Selection of subsequent therapy will depend on patient disease status, comorbidities, and resource availability.
The NCCN Guidelines for Kidney Cancer have undergone a major shift in the risk categorization used for designating “preferred” and “other recommended” or “useful under certain circumstances” first-line treatments. In the most recent version of the guidelines, “favorable risk” is now its own risk category and “intermediate risk” and “poor risk” are combined into one category. The treatment recommendations for clear cell renal cell carcinoma are continually revised and more new options are anticipated based on encouraging results from pivotal trials. In his presentation at the NCCN 2019 Annual Conference, Dr. Jonasch described these promising findings.
Several updates were made to the 2018 NCCN Guidelines for Kidney Cancer. Adjuvant sunitinib is the first adjuvant therapy to be endorsed by the panel for patients with stage II and III clear cell histology renal cell carcinoma (RCC; category 2B). A promising new treatment—ipilimumab plus nivolumab for patients at intermediate and poor risk in the frontline setting—was added to the guidelines as well. Cabozantinib was added as a first-line option for poor- and intermediate-risk patients with advanced RCC.
Robert W. Carlson and Eric Jonasch
NCCN has developed a series of Evidence Blocks: graphics that provide ratings for each recommended treatment regimen in terms of efficacy, toxicity, quality and consistency of the supporting data, and affordability. The NCCN Evidence Blocks are currently available in 10 tumor types within the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). At a glance, patients and providers can understand how a given treatment was assessed by the NCCN Guidelines Panel and get a sense of how a given treatment may match individual needs and preferences. Robert W. Carlson, MD, CEO of NCCN, described the reasoning behind this new feature and how the tool is used, and Eric Jonasch, MD, Professor of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, and Vice Chair of the NCCN Kidney Cancer Panel, described its applicability in the management of metastatic renal cell carcinoma.
Eric Jonasch and Robert J. Motzer
Thai H. Ho and Eric Jonasch
Hereditary forms of renal cell carcinoma (RCC) have yielded clues regarding the molecular pathogenesis of sporadic RCC. The discovery of germline mutations in chromatin-modulating enzymes also defined a new hereditary RCC syndrome. Although histologically distinct RCC subtypes exist, emerging themes shared between hereditary and sporadic RCC include dysregulation of the von Hippel-Lindau tumor suppressor protein/hypoxia inducible factor axis, defective ciliogenesis, and aberrant tumor metabolism. This article describes the most common hereditary RCC syndromes and associated extrarenal manifestations. Recent evidence supports developing screening guidelines for early-onset RCC to identify persons with germline mutations in the absence of secondary clinical manifestations.
Gary R. Hudes, Michael A. Carducci, Toni K. Choueiri, Peg Esper, Eric Jonasch, Rashmi Kumar, Kim A. Margolin, M. Dror Michaelson, Robert J. Motzer, Roberto Pili, Susan Roethke and Sandy Srinivas
The outcome of patients with metastatic renal cell carcinoma has been substantially improved with administration of the currently available molecularly targeted therapies. However, proper selection of therapy and management of toxicities remain challenging. NCCN convened a multidisciplinary task force panel to address the clinical issues associated with these therapies in attempt to help practicing oncologists optimize patient outcomes. This report summarizes the background data presented at the task force meeting and the ensuing discussion.