ASCO GU 2017: Evolving Treatment Using Tyrosine Kinase Inhibitors and Immunotherapy in Metastatic Renal Cell Carcinoma - Session Highlights
Orlando, Florida USA (UroToday.com) Dr. Eric Jonasch stated it is well-known that tumor cells present antigens, which, in turn, are identified by CD8 T-cells, thus activating an immune response. Several receptors and ligands attenuate this immune response, such as CTLA4, programmed death-1, and programmed death-ligand-1. However, there are many more checkpoints that may serve as treatment targets. Some tumor cells lack the ability to attract immune cells and are immunologically cold. Other cells have plenty of immune cells, but they also activate too many checkpoints. Each scenario requires a different therapy approach: monotherapy, a combination with other targeted therapies, a combination of checkpoint inhibitors, and the use of biomarkers. The effect of nivolumab vs. everolimus has been examined, showing that the objective response rate was better for nivolumab. A significant proportion of patients in both arms, though, had a progressive disease that underlined the need for combination therapy. In many trials, it was apparent that antiangiogenic-treated tissues were associated with increased tumor-infiltrating T-cells, and this high T-cell population leads, in turn, to a worse clinical outcome. Furthermore, treated tissues are linked with an increased programmed death-ligand-1 expression, and it is clear from these results that there is a need to both augment T-cell ingress and improve immune response. In phase-I trials, combining tyrosine kinase inhibitors and checkpoint inhibitors has shown an objective response benefit. The IMmotion 151 Trial is a phase-III study of atezolizumab teamed with bevacizumab vs. sunitinib in untreated advanced renal cell carcinoma, withresults pending.
Lastly, there is a dire need for clinical relevant biomarkers that will help select patients for checkpoint inhibitor therapies. At this point, we lack the ability to predict which patients will benefit most from the various combination therapies. In the future, Dr. Jonasch predicted that we will learn how a tumor's mutations influence its interaction with T-cells, but he concluded that we also need to create liquid biopsy techniques to determine treatment benefit.
Presenter: Eric Jonasch, MD, MD ANDERSON CC, USA
Written By: Miki Haifler, MD, M.Sc, Fox Chase Cancer Center