Mario Sznol, MD
Immunotherapy agents have quickly become a standard choice in both the frontline and second-line settings of renal cell carcinoma (RCC), explains Mario Sznol, MD.
, Sznol, a professor of Medicine (Medical Oncology) at Yale Cancer Center, discusses the current state of immunotherapy in RCC, emerging agents and combinations in the field, and the challenges that arise with finding biomarkers.
OncLive: What should oncologists understand about immunotherapy in RCC?
: I want them to understand that immunotherapy should be considered as both a frontline and second-line option for metastatic kidney cancer. Although the targeted agents against VEGF give us a lot of activity, they usually don’t give us durable remissions. Once you come off of those agents, the disease usually progresses and patients usually progress while they are on those agents.
Obviously, every patient is different. Some of them must get VEGF inhibitors or mTOR inhibitors first.
How are you currently treating patients in the second-line setting?
The first question is, “How do we treat frontline?” We’re trying immunotherapies in the frontline setting, even though they’re not approved. We either give IL-2 or anti–PD-1—if we can get it—or we put them on a clinical trial that is an anti–PD-1 combination.
We try to give them a second-line immunotherapy if we’re able to. If those agents fail, then we give them a VEGF-targeted agent. However, in patients who receive an antiangiogenesis agent first, like sunitinib or axitinib (Inlyta) where they have had a couple lines of antiangiogenesis agents, we give nivolumab. Now, we have an interesting third-line option—though it is not an immunotherapy—which is cabozantinib (Cometriq).
Does the survival benefit that nivolumab has shown set a new standard?
In a sense, yes. However, although nivolumab is a good agent, we have a long way to go.
It does improve survival. There are few patients who have long durable remissions, but we are not curing the majority of patients. Yes, it sets a new standard. However, maybe ipilimumab/nivolumab may be the next step. VEGF-targeted agents with anti–PD-1/PD-L1 might be the next step.
How do you have the conversation on immunotherapy with your patients?
If they are appropriate candidates, I basically tell them there are 3 therapies. There are immunotherapies, VEGF-targeted therapies, or the mTOR inhibitors. I try and explain the risks and benefits of each, but I try and emphasize that the immunotherapies can, in some patients, give durable remissions, and actually have a favorable toxicity profile in general.
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