How will advanced renal cell carcinoma treatment evolve? An interview with Paul Nathan

Written by Paul Nathan (Mount Vernon Cancer Centre (Northwood, UK)

renal cell carcinoma

Please introduce yourself, your research background and current research interests.

My name is Paul Nathan, and I am a consultant medical oncologist at the Mount Vernon Cancer Centre (Northwood, UK). I have a specialist interest in the management of kidney cancer and melanoma. I’ve recently stood down from chairing the NCRI clinical studies group for bladder and renal cancer. My interests are very clinically driven and we therefore run a large clinical trial portfolio. Over recent years that’s obviously included combinations of immunotherapy agents as well as combinations of immunotherapy and targeted  therapies. I was an investigator on the axitinib and avelumab study that has resulted in recent Cancer Drugs Fund approval and I was an external witness at the NICE meeting.

What are the currently available treatments for advanced renal cell carcinoma?

Up until recently, treatments for metastatic kidney cancer were based solely on anti-angiogenic targeted therapies that affect tumour vasculature. They were our main first and subsequent lines of therapies. Over the last few years, immunotherapy has been introduced initially as a second-line therapy as a single agent (nivolumab) and more recently, as a first-line option as combination immunotherapy with ipilimumab and nivolumab.

The most recent advance pairs up those two categories of drugs, so it’s a combination of an immunotherapy drug like avelumab with an anti-angiogenic, anti-blood vessel drug axitinib. We’ve been using each of these types of drugs for kidney cancer for a while. This is the first NICE approved cross-combination of an immunotherapy drug paired with an anti-angiogenesis drug.

What are some of the challenges that need to be overcome to advance treatment for advanced renal cell carcinoma?

Renal cell cancer has been a historically difficult cancer to treat. It’s effectively unresponsive to legacy chemotherapy and treatment has recently been based upon anti-angiogenic treatments and immunotherapy treatments. Now the challenge is that we have treatments that can help significant numbers of patients, but the proportion of patients who have long-term durable benefit is still a minority. Our challenge is therefore trying to uplift the proportion of patients who can derive longer term benefits from these treatments.

Could you tell us about the recent approval for first-line treatment of advanced renal cell carcinoma focusing on what this approval brings to the field?

The approval is with the combination of axitinib and avelumab. Axitinib is anti-angiogenic targeted therapy and avelumab is an immunotherapy, an antibody against PD-L1. The trial, the JAVELIN 101 study, compared the combination of axitinib and avelumab in a Phase III study against sunitinib, which is another anti-angiogenic targeted therapy that is still a standard of care for advanced kidney cancer.

The trial design was a large study, there were over 440 patients on each arm, so 886 patients were included. What the study showed was that the combination was superior to sunitinib, both in terms of progression free survival and response rate. The overall improvement in progression free survival for the whole population of patients was a 31% reduction in the likelihood of progression or death in patients who had the combination treatment compared with single agent sunitinib. The response rate (the number of patients who experience significant tumour shrinkage) with the combination of axitinib and avelumab was double that of sunitinib, so it does look like a major impact and a major improvement on this disease.

How do you hope to see the treatment landscape of renal cell carcinoma evolve over the next 5–10 years?

The challenge of trying to uplift the number of patients who have durable benefit will depend upon novel combinations with an immunotherapy backbone. The durability of responses will be delivered by the immunotherapy components of these combinations. What we need to do is to add or develop novel combinations with an immunotherapy backbone that will increase the number of patients who derive durable benefit.

The opinions expressed in this Interview are those of the author and do not necessarily reflect the views of Oncology Central or Future Science Group.