First-line treatment options for metastatic clear cell RCC

Chung-Han Lee, MD: Let’s switch gears a bit and talk a bit about first-line treatment for people with metastatic kidney cancer. From 2022, most of our treatments for metastatic clear cell kidney cancer will rely on backbone immunotherapy. We are talking about combination therapy to treat kidney cancer. Immunotherapies work by stimulating your own immune system so that your immune system finds and fights kidney cancer.

There are 2 main approaches people take when deciding how to treat the condition. One approach is to use 2 different immune checkpoint inhibitors. It’s basically using 2 drugs that work by boosting the immune system. The other approach is to use a tyrosine kinase inhibitor, or TKI. These are specific targeted therapies that attack and alter the microenvironment in the blood vessels that feed kidney cancer. For a very long time, this has been the mainstay of treatment for people with metastatic disease.

How to choose between these therapeutic approaches? One thing that is extremely important is to think about the patient and to individualize care for specific patients. This means considering their age, other health conditions they have, and their social environment in terms of how they would tolerate various treatments. Or if they’ve had a problem, what’s their support system like?

The other thing that has become critical is to think about their risk stratification with respect to their kidney cancer. There are several risk stratification schemes that classify patients into favorable, intermediate, or low risk disease. This clinically takes into account your blood tests. It looks at when your kidney cancer was diagnosed and how long it takes you to need systemic treatment. It also looks at people who have other comorbidities and how symptomatic they are of their disease. We integrate this to arrive at a group of risk related to treatments.

When we think of screening, assuming they are healthy patients who are otherwise in one of the risk categories, including favorable, intermediate, and low risk disease, the approved approach and recommended by treatment guidelines is a combination of a tyrosine kinase inhibitor and an immune checkpoint inhibitor. In this combination, one drug targets the blood vessels that feed kidney cancer, and one drug boosts the immune system.

For sicker patients with intermediate or high risk disease, the other potential option is a combination of the 2 immunotherapy drugs. When it comes to the 2 immunotherapy drugs versus tyrosine kinase inhibitor plus immune checkpoint inhibitor, these 2 approaches have never been compared head-to-head. However, they have both been shown to be better than using the tyrosine kinase inhibitor alone. It’s a pretty in-depth discussion that people often have with their oncologists about which of these approaches is best for them.

Transcript edited for clarity.

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