Q&A: The Latest Advances in Kidney Cancer Treatment and Research

Treatment for kidney cancer, particularly clear cell renal cell carcinoma, the most common subtype, has evolved rapidly in recent years. New immunotherapies, targeted drugs, and combination approaches are expanding options for patients and improving outcomes. 

Karie Runcie, MD, a medical oncologist specializing in kidney cancer, explains what these advances mean for patients today and where the field is headed next. 

How would you describe the current landscape for kidney cancer treatment, and in particular clear cell renal carcinoma?

The treatment landscape for clear cell renal cell carcinoma has changed significantly over the past decade, and we now have more effective options than in the past. Today, medical treatment for clear cell renal carcinoma is largely built around two main strategies: immunotherapy, which helps the immune system recognize and attack cancer, and targeted therapies, which block key pathways that tumors use to grow. 

Another important change is that instead of giving one drug at a time, we now often use combinations, which has improved how well treatments work and how long patients respond to these treatments. 

We’re also starting to use some of these therapies earlier in the course of disease, including after surgery (adjuvant therapy) for patients at higher risk of recurrence. Altogether, these advances are helping us move toward more durable and effective outcomes.

What role does adjuvant therapy play for patients?

Adjuvant therapy, treatment given after surgery to reduce the risk that the cancer comes back, is an area where we’ve seen meaningful progress. 

For patients with higher-risk kidney cancer, one year of immunotherapy with pembrolizumab is now a standard option, based on the phase III KEYNOTE-564 trial. This approach has been shown to improve outcomes compared to observation alone. 

The field is also moving beyond single-agent adjuvant immunotherapy towards using combination approaches, including adding newer targeted therapies to immunotherapy.  

As these approaches evolve, an important focus will be balancing added benefit with potential side effects. For now, adjuvant therapy remains an important option for carefully selected high-risk patients. 

Beyond immunotherapy, what newer targeted treatments are emerging?

A newer class of targeted drugs focuses on a pathway called HIF-2α, which is central to how many kidney cancers develop and grow. Belzutifan, the first drug in this class of HIF-2α inhibitors, represents a more precise, biology-driven approach to treatment. 

This therapy is already being used in certain settings and is being studied more broadly, including in combination with immunotherapy in the adjuvant setting and potentially earlier in the course of disease. 

At the same time, new immune-targeted strategies are emerging beyond traditional checkpoint inhibitors. Bispecific T-cell engagers, such as ENPP3 x CD3 constructs, which works by redirecting T cells to kidney cancer cells, are one such new drug that has shown early signs of activity. We have a clinical trial here at Columbia that is open and enrolling for this very new and promising therapy. 

 In addition, cell therapy approaches are beginning to enter the field, particularly CD70-directed CAR T-cell therapies. While still investigational, these approaches reflect the next wave of innovation in the field. 

Why are combination therapies now such a central part of treatment?

Kidney cancer is driven by multiple biological processes at once, including tumor growth, blood vessel formation, and the ability to evade the immune system. 

Because of this complexity, a single therapy is often not enough. Combination approaches allow us to target multiple pathways at the same time, which can improve both how well treatment works and how long it lasts. 

At Columbia, we are studying novel combinations in clinical trials, including the EXACT trial, which we designed to evaluate a next-generation tyrosine kinase inhibitor alone or combined with immunotherapy for patients whose cancer has progressed after adjuvant therapy, which is a very unique patient population.  . 

We are also participating in the ARCITECT trial, which pairs two immunotherapies, botensilimab and balstilimab, designed to enhance the immune response in complementary ways. 

In some cases, these therapies may also work synergistically—for example, by making tumors more visible to the immune system. Combination strategies also can address the challenge of tumor heterogeneity, meaning tumors are made up of different types of cancer cells that rely on different pathways. Overall, combination strategies give us a better chance of achieving meaningful and sustained disease control.

Looking ahead, what gives you the most optimism in kidney cancer research? 

There is a great deal of momentum in the field right now. We are seeing the development of new drugs that target kidney cancer in more precise ways, along with next-generation immunotherapies that build on what we’ve already learned. At the same time, newer approaches such as cell-based therapies are beginning to be explored in kidney cancer, with the potential to deliver highly targeted and durable responses. 

Together, these advances are moving us toward a future where treatment is not only more effective, but also more personalized for each patient.