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Immunotherapy a Mainstay in Kidney Cancer, Novel Approaches on Horizon

Gina Columbus @ginacolumbusonc
Published: Tuesday, Mar 22, 2016

Dr. Mario Sznol

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.

Nivolumab (Opdivo), which was approved by the FDA for the treatment of metastatic RCC after the failure of an angiogenesis inhibitor in November 2015, is proving to be an appropriate choice for select patients, Sznol says.

The CheckMate-025 study, which led to the FDA approval, compared the efficacy of nivolumab with everolimus (Afinitor). In the study, patients who received nivolumab had a median overall survival of 25.0 months compared with 19.6 months in those who received everolimus (HR, 0.73; P = .002).

Aside from nivolumab, high-dose interleukin-2 (IL-2) is also a go-to regimen for patients.

Building on this foundation, emerging anti–PD-1/PD-L1 therapies are on the horizon to potentially provide additional options to patients. Ongoing studies are also looking at combination strategies, such as checkpoint inhibitors plus VEGF-targeted agents.

In an interview with OncLive, 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?

Sznol: 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.

In some cases, patients on immunotherapy can get durable remissions. With high-dose IL-2, some patients can possibly be cured of their disease, or at least have very long remissions that can last for many yeas.

I think physicians ought to be first thinking about immunotherapies, try and give patients durable remissions, and then come back with targeted agents when those fail.

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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