Dr Margulis on Key Considerations When Navigating Frontline Combination Regimens in RCC

Vitaly Margulis, MD, urologic oncologist, Harold C. Simmons Comprehensive Cancer Center, professor, urology, Paul C. Peters, MD, Chair in Urology, UT Southwestern Medical Center, discusses key disease characteristics and patient factors to consider when selecting between immuno-oncology (IO)/IO vs IO/TKI treatment combinations for the management of patients with renal cell carcinoma (RCC).

With the expansion treatment approaches in RCC in recent years, several questions have emerged regarding the selection and sequencing of available immunotherapy and targeted therapy options, particularly in the context of metastatic disease, Margulis begins.

Combination strategies have largely replaced single-agent therapy as the standard frontline approach in this space, Margulis asserts. Accordingly, one key question is whether the initial treatment should consist of an immune checkpoint inhibitor doublet or an immune checkpoint inhibitor and targeted therapy combination, he says.

Another pivotal aspect of treatment approaches in RCC from a surgical perspective is the management of a patient’s primary tumor, Margulis adds.

Clinicians may decide to promptly address the tumor, or may elect to initially administer systemic therapy with plans to reevaluate and address the primary tumor if necessary, he says. These deliberations underscore the complexities surrounding treatment decision-making in RCC.

Several patient factors also influence treatment decisions, Margulis continues. For instance, patients who exhibit bulky symptomatic disease may benefit more from an immune checkpoint inhibitor/TKI combination, Margulis explains, noting that this approach has been shown to rapidly reduce disease burden and alleviate symptoms. Notably, the addition of a second immune checkpoint inhibitor later on in the treatment course may be considered, he adds.

Conversely, treatment selection for patients with relatively stable, asymptomatic disease, who fall within intermediate and high-risk categories, is more varied, Margulis states. IO/IO combinations are an attractive option in this space, as they offer the greatest probability of achieving deep and sustained responses, he details. In comparison, treatment with a checkpoint inhibitor and TKI may yield rapid responses, but are less likely to produce long-term or curative outcomes, he says.

Taken together, these considerations emphasize the importance of tailoring therapies to individual patient needs and disease characteristics, Margulis concludes.