First SITC Guidelines in RCC Address Continuing Role of Interleukin-2 and Emergence of Nivolumab

Ariela Katz
Published: Tuesday, Feb 21, 2017
Brian Rini, MD

Brian Rini, MD

New guidelines involving the immunotherapies nivolumab (Opdivo) and interleukin-2 (IL-2) have been issued by The Society for Immunotherapy of Cancer (SITC) to help practicing clinicians manage patients with renal cell carcinoma (RCC). The updated guidelines are needed because 10 agents have been approved for the treatment of patients with metastatic clear cell RCC, which accounts for 75% to 85% of all cases of metastatic RCC (mRCC) during the past 11 years. Meanwhile, new immunotherapies continue to enter the clinical arena.

For many years, immunotherapies, including interferon-alpha (IFN) and IL-2, have been used to successfully treat patients with mRCC. Newer therapies have been on the rise, however, such as vascular endothelial growth factor (VEGF) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and immune checkpoint inhibitors.

“Kidney cancer has always been considered to be a disease amenable to immunotherapy but until recently, there had never been any guidelines about the use of IL-2 or nivolumab and some of the emerging agents, so the guide- lines are designed to lay the groundwork as these agents get further developed in RCC,” said Brian Rini, MD, professor of medicine at Cleveland Clinic’s Taussig Cancer Institute and 1 chair of the 20 members of the task force assembled to create the guidelines. This consensus statement is the second publication to come out of SITC’s Cancer Immunotherapy Guidelines initiative, which was expanded in 2014 to include genitourinary malignancies. Currently, SITC has immunotherapy guidelines for prostate and kidney cancer, with guidelines for bladder cancer coming soon.

Unlike the National Comprehensive Cancer Network (NCCN)’s guidelines, which feature a broad range of treatment regimens, the guidelines from SITC’s task force are meant to demonstrate how treating urologists should assess and guide immunotherapy treatments for eligible patients under their care. The intention is also to set the stage for future immunotherapeutic developments in RCC.

“Although the NCCN guidelines are a list of drugs across mechanisms within a particular disease,” Rini says, “this is really meant to focus on immunotherapy and also how it fits into that big picture [of kidney cancer treatment].” This also gives the guidelines a more pointed focus, rather than retreading on known procedures.


Stage IV Renal Cell Carcinoma (RCC) Immunotherapy Treatment Algorithm

Stage IV Renal Cell Carcinoma (RCC) Immunotherapy Treatment Algorithm

Stage IV renal cell carcinoma (RCC) immunotherapy treatment algorithm. All treatment options shown may be appropriate. The final selection of therapy should be individualized based on patient eligibility and the availability of each therapy at the treating physician’s discretion.

  1. “Risk” refers to prognostic risk group per Memorial Sloan Kettering Cancer Center (MSKCC) and/or International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) classification.
  2. For patients with small-volume, indolent metastases, an initial period of observation can be considered accounting for patient age/comorbidities, patient preference, and toxicity of available therapy.
  3. A clinical trial, including those that are immunotherapy-based, should be considered in all RCC patients in all lines of therapy.
  4. As noted in the manuscript, HD IL2 should be considered and discussed with mRCC patients with clear cell histology and good performance status.
  5. For patients with advanced non-clear cell renal cell carcinoma (RCC), if available a clinical trial is the preferred initial treatment option, including trials of checkpoint inhibitors for which limited data exists regarding efficacy in non-clear cell RCC. If unavailable, then a VEGFR tyrosine kinase inhibitor (TKI) is preferred given results from two small randomized trials showing a slight advantage over mTOR inhibitors in this setting. 
  6. Nivolumab is an appropriate initial recommendation in refractory RCC in the absence of contraindications given the overall survival benefit and tolerability. Other options (TKI, HD IL-2 and mTOR inhibitors) can be considered depending on patient performance status, comorbidities, prior therapy received and preference.
Reprinted from SITC consensus statement on immunotherapy for the treatment of renal cell carcinoma, originally published in the Journal of Immunotherapy Cancer1


One main focus, Rini goes on to explain, is “the role of IL-2, the selection of patients for that particular therapy, and the same for nivolumab; how it’s going to be used, duration of treatments, and optimal application of both of those agents, which are obviously the main immunotherapies used in kidney cancer.” Optimal sequencing is becoming even more important in order to provide patients with the greatest chance of durable disease control and survival that is free from symptoms of disease or treatment.

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