First-Line Treatment Options for Metastatic Clear Cell RCC

Chung-Han Lee, MD: Let’s shift gears a little and talk a little about first-line treatment for people with metastatic kidney cancer. As of 2022, most of our treatments for metastatic clear cell kidney cancer build upon an immunotherapy backbone. We’re talking about combination therapy in order to treat the kidney cancer. Immunotherapies work by boosting your own immune system to have your immune system find and fight off the kidney cancer.

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

How does one decide between these treatment approaches? One thing that’s critically important is thinking about the patient and individualizing care for specific patients. This means thinking about their age, other medical conditions that they have, and their social environment in terms of how they’d tolerate various treatments. Or if they ran into an issue, what’s their support system like?

The other thing that has become critical is thinking about their risk stratification from their kidney cancer. There are multiple risk stratification schemes that classify patients into either favorable-, intermediate-, or poor-risk disease. This takes into clinical consideration your blood work. It looks at when your kidney cancer was diagnosed and the time it takes for you to need systemic treatment. It also looks at people who have other comorbidities and how symptomatic they are from their disease. We integrate that to come up with a risk group related to the treatments.

When we think about selection, assuming that these are healthy patients who otherwise are in any of the risk categories—including favorable-, intermediate-, and poor-risk disease—the approach that’s approved and recommended by treatment guidelines is a combination of a tyrosine kinase inhibitor and an immune checkpoint inhibitor. In that combination, one drug targets the blood vessels that feed the kidney cancer, and one drug boosts the immune system.

For sicker patients with intermediate- or poor-risk disease, the other potential option is a combination of the 2 immunotherapy drugs. In regard to the 2 immunotherapy drugs vs the tyrosine kinase inhibitor plus immune checkpoint inhibitor combination, 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 by itself. It’s a fairly extensive discussion that people often have with their oncologists with regard to which of those approaches makes the most sense for them.

Transcript edited for clarity.