Nivolumab improves overall survival for advanced kidney cancer

Prof Padmanee Sharma - MD Anderson Cancer Center, Houston, USA

What is the headline information of your presentation?

I’m presenting the CheckMate-025 clinical trial which is a phase III clinical trial that randomised previously treated patients with metastatic renal cell carcinoma to either treatment with nivolumab, an immune checkpoint therapy agent, or everolimus, which is a standard of care agent.

Can you describe your methods?

We randomised over 800 patents, 410 in the nivolumab arm, 411 in the everolimus arm, to treat… it was a one to one randomisation so that patients got treatment with either nivolumab or everolimus. The patients were treated until disease progression or until toxicities that they could not tolerate the drug.

What are your findings?

What we saw was that the nivolumab treated patients had an overall survival benefit of 25 months for the median overall survival versus the everolimus treated patients who had an overall survival benefit of median overall survival of 19.6 months. This was statistically significant, meaning that the nivolumab allowed patients to live longer and provided a survival benefit.

Can you put these results in context with regards to current practice?

Currently most of the patients who are receiving treatment for metastatic renal cell carcinoma in the second line setting are receiving agents that target the tumour cells and these are tyrosine kinase inhibitors or antiangiogenic agents. What we’re trying to say is that an immune checkpoint therapy agent can also be beneficial and provide a survival benefit. Most of the other trials also looked at progression free survival; this is the first time in a phase III clinical trial that we’re looking at overall survival and that is really the gold standard for saying whether or not patients are doing well with a therapy. So far what we’re seeing is we have the potential now for a new therapy that can give patients the survival benefit.

Were there any adverse effects?

So the adverse events were what we would normally expect with nivolumab and have been previously published. We did not see any new safety signals. What we did see was that there were fewer high grade adverse events, the grade 3/4 adverse events, there were fewer of those in the nivolumab treated patients than the everolimus treated patients and there were no treatment related deaths with nivolumab.

What is the concluding message for doctors?

I think that we have a new treatment, hopefully, that we can think about for our patients, that we can think about an immune checkpoint agent now, nivolumab, being hopefully considered as a treatment option for patients who were previously treated with metastatic renal cell carcinoma. We don’t know what’s going to happen in terms of approval but it was given designation breakthrough status so we hope to see that as now a new treatment option that can give our patients not only a survival benefit but hopefully durable survival benefit.

Is there potential for combination with other drugs?

Absolutely. So currently nivolumab is being combined with another new checkpoint agent, ipilimumab or anti-CTLA4, and that clinical trial is underway in the phase III clinical trial setting for patients who are previously untreated, so in the first line setting, for patients with metastatic renal cell carcinoma. So that phase III clinical trial has a combination of nivolumab plus ipilimumab versus sunitinib and we’ll wait to see what that data has. There are other combinations that are being tested in the phase I/II setting, including combinations with antiangiogenic agents or tyrosine kinase inhibitors or even radiation therapy or cryoablation.