San Antonio, Texas USA (UroToday.com) Immunotherapy and its application to advanced renal cell carcinoma (RCC) has begun to come of age over the past 2-3 years. Tumor cells (including renal cell carcinoma) are a lot like normal cells in that they have the ability to tell the immune system to “go away” using checkpoints.
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In order to reinvigorate the immune system, checkpoint inhibitors have been used. Interestingly, some tumors lack the ability to attract immune cells while others have plenty of immune cells, but have too many checkpoints. Moreover, there is evidence to suggest worse prognostic outcomes for tumors with higher proportions of immune infiltrate. Therefore, a major focus of ongoing trials remains determining specific subpopulations for which immune checkpoint blockade will be most effective.
Dr. Jonasch provided a nice overview of some of the clinical trials both completed and developing in this space. Motzer and colleagues (NEJM 2015, 373: 1803) demonstrated improved overall survival for patients with advanced RCC receiving nivolumab versus everolimus. While the trial met this primary endpoint, supplemental tables demonstrated a relatively high rate of progressive disease in the nivolumab arm compared to everolimus. Therefore, combination therapies are being increasingly explored and there are a multitude of currently registered phase I-III trials in this space (RAPID, IMmotion 151, Javelin Renal 100, Checkmate 214, etc.). One important component of all trials remains defining biomarkers to better understand the sub-populations in which the increasingly complex immunotherapy environment offers the highest efficacy. For example, PD-L1 staining is not predictive of response to therapy. However, patients with long term complete responses to anti PD1 therapy have trends towards increased CD98 infiltrate and increased expression of proinflammatory cytokines. Thus, a better understanding of appropriate clinical scenarios in which immune therapies can be applied is key to improving care in this challenging patient population.
Presented By: Eric Jonasch, MD
Written By: Benjamin T. Ristau, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center
17th Annual Meeting of the Society of Urologic Oncology - November 30 -December 2, 2016 – San Antonio, Texas USA