Sandy Liu, MD: Talking about the landscape of kidney cancer, it’s actually very exciting and remarkable. Prior, in the 1990s, we just had cytokine therapy, interleukin-2 and interferon, which have not been that effective. Interleukin-2 was the only therapy we had actually been able to possibly cure patients with, but that was just 5% to 7% of the time. The rest of the time, there were really no good options, and patients generally did not do as well. Starting from about 2005, we have had targeted agents approved, and that has dramatically changed the landscape of kidney cancer. We have these targeted agents, which are targeted (toward) blood vessel formation, or angiogenesis, and that has led to a dramatic increase in progression-free survival in these patients. Patients are actually living longer with more options.
The current landscape, after these targeted agents were approved, is starting with oral agents first line in stage 4 advanced disease. Targeted agents such as Sutent (sunitinib) and Votrient (pazopanib) have been approved and recommended in the first-line setting. Lately, in December of 2017, we just had a new targeted agent approved, and that’s called cabozantinib. Cabozantinib was actually studied head-to-head with sunitinib, and it outperformed sunitinib in terms of having better control of the disease and progression-free survival. Now what I have been recommending is more cabozantinib in the first-line setting.
However, although these oral agents have proven to be very, very, very effective, we have used another form of therapy called immunotherapy, or checkpoint inhibitors. They have been on the landscape since about 2015. They’ve been approved for several other kinds of cancer like lung cancer, melanoma and bladder cancer. But in about 2016, one immunotherapy called nivolumab was actually approved in kidney cancer in the second-line setting.
We wanted to test it in the first-line setting with combination immunotherapy, 2 immunotherapies, to try to stimulate the immune system and attack the cancer cells. That was with ipilimumab and nivolumab. What that has shown is a dramatic survival benefit over the oral agent: not the targeted agents that target blood vessels but another agent called an mTOR (mechanistic target of rapamycin) inhibitor, everolimus. That has also been approved for kidney cancer. When they compared the immunotherapy combination ipilimumab plus nivolumab to everolimus in the first-line setting, it showed a dramatic response compared with everolimus, as well as an overall survival benefit. This was seen mainly in intermediate- and poor-risk patients. Now it has been approved, so we are able to give combination immunotherapy in the first-line setting.
For every patient I see, I always consider a clinical trial. When I meet a patient for the first time and I think they’re a good clinical trial candidate, if I have clinical trials available in the first-line setting, I will recommend them. We actually do have a clinical trial available that combines immunotherapy and targeted therapy, which is really exciting, and that’s in the first-line setting. In the second-line and third-line setting, I do have clinical trials. If I do not have clinical trials, I reach out to my colleagues at other academic centers to see if they have clinical trials, and I would recommend that. Clinical trials are always my first option. If they’re not a good candidate or if there are no trials available, I would consider standard of care.