Dr Matrana on Advantages and Challenges of the Expanding First-Line RCC Treatment Paradigm

“Trying to decide whether every patient needs combination therapy, or if some [patients may] respond [to a single-agent treatment] has been a challenge and muddied the waters in some ways. We’re almost at a spot where we have too many great therapies in RCC [and are] left with the challenge of selecting the best treatment for each patient.”

Marc Matrana, MD, director of the Precision Cancer Therapies (Phase I) Research Program at the Louisiana Cancer Research Center, part of the Ochsner Health System, discussed the evolution of first-line treatment strategies for patients with renal cell carcinoma (RCC).

Historically, the therapeutic paradigm for previously untreated RCC was limited to agents like high-dose IL-2 and interferon alfa, which are associated with substantial toxicity and modest efficacy, Matrana began. However, in 2025, there are now several highly effective combination regimens capable of achieving disease control in approximately 95% to 98% of patients, he stated.

Despite these advances, the optimal selection of therapy remains a complex issue, according to Matrana. Determining whether all patients require combination therapy or whether a subset may derive sufficient benefit from single-agent treatment continues to be a subject of clinical uncertainty, he noted. In many respects, the abundance of highly active therapeutic options for RCC presents a new challenge: identifying the most appropriate regimen for individual patients, he reported.

Matrana often explains to patients that the most effective therapy is ultimately the one that works for them; however, currently, the only method to determine the optimal therapy for each patient is through empirical treatment. An urgent need that is lacking in RCC is a reliable, actionable predictive biomarker akin to prostate-specific antigen in prostate cancer, he explained. Such a biomarker would enable a more personalized approach to therapy selection by predicting treatment response, he said. Although there is growing enthusiasm around several emerging biomarker candidates, prior efforts have not produced a clinically validated tool for predicting therapeutic benefit in RCC, he emphasized. However, Matrana concluded that he remains hopeful that a transformative biomarker will emerge in the near future.