"For the first time an immune checkpoint inhibitor has been proven to increase survival among patients with advanced renal cell carcinoma RCC a patient population for whom treatment options are currently limited.  Researchers at The University of Texas MD Anderson Cancer Center demonstrated a median overall survival benefit of  months with nivolumab a Food and Drug Administration FDAapproved immunotherapy agent compared with . months for everolimus a current standard of care for patients with metastatic kidney cancer.  Published online by the New England Journal of Medicine and being presented this week at a Presidential session of the European Cancer Congress ECC the findings of CheckMate provide definitive evidence that an immune checkpoint inhibitor is a valid treatment strategy for patients with advanced RCC and supports a paradigm change in the standard of care treatment according to the authors. Nivolumab marketed as Opdivo is currently used to treat metastatic melanoma and advanced nonsmall cell lung cancer. CheckMate is an example of how investigators are examining approved immunotherapy drugs to determine potential impact on other tumor types. Immunotherapy has long been believed to have the potential to make an impact in kidney cancer but until now we had not been able to demonstrate such a significant survival benefit. We have a real opportunity to change clinical practice for patients when other therapies have failed said principal investigator Padmanee Sharma MD PhD professor Departments of Genitourinary Medical Oncology and Immunology and scientific director of the Immunotherapy Platform part of MD Andersons Moon Shots Program.  Through studies such as CheckMate we are learning to target the patients immune systems to fight cancer rather than targeting the tumor itself. This is a new way forward. In the randomized phase III clinical trial patients whose disease progressed on antiangiogenic therapies were treated with either nivolumab or everolimus. Median overall survival was . months longer with nivolumab  months compared with everolimus . months.  The study included  patients with advanced RCC across  sites in  countries in North America Europe Australia South America and Asia. All had previously been treated with one or two antiangiogenic therapies drugs that inhibit the growth of new blood vessels a critical component of cancer development. The median duration of treatment was . months with nivolumab and . months with everolimus.  In addition to demonstrating increased overall survival the researchers showed a higher objective response rate  the number of patients who respond to the treatment  with nivolumab. Of the  patients enrolled  responded to nivolumab versus  of those treated with everolimus.  Among these patients partial responses were observed in  of those treated with nivolumab and  of patients treated with everolimus complete responses were observed in  four patients treated with nivolumab and fewer than  two patients treated with everolimus. Further among patients who showed a response the impact was durable according to Sharma. While median progressionfree survival appeared similar between treatments . months and . months with nivolumab and everolimus respectively when researchers explored a delayed progressionfree survival benefit at six months they reported . months with nivolumab and . months with everolimus. This ongoing response was observed among  of those treated with nivolumab and  of those treated with everolimus. More than  months later  and  of patients treated with nivolumab and everolimus respectively continued to show a response. For some patients even after treatment with nivolumab ended response to the drug continued. The immune system has a memory so even when treatment has stopped the body continues to exhibit a longterm response  meaning these patients can live normal lives without progressive disease. Finally the investigators observed fewer treatmentrelated adverse events including fatigue and nausea and improved quality of life with nivolumab.  Trial halted early breakthrough therapy designation granted by FDA  These results led the trial to be halted early in July  when an assessment conducted by the independent Data Monitoring Committee DMC concluded that the study met its primary endpoint demonstrating superior overall survival in patients receiving nivolumab. Nivolumab blocks a T cell inhibitory signaling pathway known as PD that controls the immune response and can prevent the immune system from attacking cancerous cells. The drug is approved for metastatic melanoma patients who show no response to other treatments and for advanced squamous nonsmall cell lung cancer NSCLC with progression on or after chemotherapy. Based on the CheckMate findings earlier this month September  the FDA granted Breakthrough Therapy Designation to nivolumab for the potential indication of metastatic RCC. The Breakthrough Therapy designation is intended to expedite the development and review of medicines with early signals of clinical benefit in serious diseases to help ensure patients have access to new therapies as soon as possible. The next questions are how do we increase the number of patients who respond and how do we move immune checkpoint agents into the frontline setting  not just using them when other therapies have failed but intervening earlier said Sharma. Were studying combination therapies to answer these questions and believe these studies will change the way we treat many cancers. Each year there are  new cases of RCC diagnosed worldwide it is the most common type of kidney cancer among adults and approximately  of patients present with metastatic disease at diagnosis according to the scientific literature. A number of targeted therapies have been approved in recent years for the treatment of advanced RCC with five antiangiogenic and two mTOR inhibitors including everolimus these drugs block a protein that regulates cell growth proliferation survival etc. showing benefits in pivotal phase III trials.  While these treatments have changed the therapeutic landscape for RCC they are associated with limited survival following emerging resistance to therapy said Sharma. The overall survival benefit shown in this study sets a new benchmark for therapeutic strategies for advanced RCC patients in need of a secondline therapy. Sharma is scientific director of MD Andersons immunotherapy platform which provides immune monitoring expertise to MD Andersons  clinical trials of immunotherapy drugs as single agents or in combinations. Platform investigators conduct research to understand which patients will benefit from immunotherapy to evaluate effective drug combinations and to identify new molecules that block or stimulate immune response. The platform is part of MD Andersons Moon Shots Program which is designed to harness scientific knowledge and develop new technologies that will dramatically reduce cancer deaths through prevention early detection and treatment."