Dr Matrana on the Persisting Need For Validated Biomarkers to Guide Treatment Selection in RCC

"Selecting which combination is right for which patient, and trying to decide if every patient needs combination therapy or will respond just one therapy or another, has really been a challenge for clinicians. What we really lack in RCC—and hopefully that will be changing soon—is a really good biomarker."

Marc R. Matrana, MD, professor of internal medicine at The University of Queensland Medical School – Ochsner Health and medical oncologist at Ochsner MD Anderson Cancer Center, underscored the ongoing need for validated biomarkers to guide treatment selection in renal cell carcinoma (RCC), particularly in the context of increasingly complex therapeutic options.

Although several immuno-oncology–based combination regimens featuring dual immune checkpoint inhibitors or an immune checkpoint inhibitor with a TKI are now available for first-line treatment of advanced RCC—including pembrolizumab (Keytruda) plus axitinib (Inlyta) from the phase 3 KEYNOTE-426 trial (NCT02853331), and nivolumab (Opdivo) plus ipilimumab (Yervoy) from the phase 3 CheckMate 214 trial (NCT02231749)—Matrana noted that treatment selection remains largely empirical. Clinicians currently lack a predictive biomarker analogous to prostate-specific antigen (PSA) in prostate cancer, which limits the ability to personalize therapy based on individual patient biology.

Matrana explained that in the absence of such a biomarker, treatment decisions are guided by clinical risk stratification models such as the International Metastatic RCC Database Consortium (IMDC) criteria and a trial-and-error approach. He emphasized that although having multiple effective combinations represents significant therapeutic progress, it also complicates clinical decision-making, especially when attempting to determine whether combination therapy is required or if select patients may respond well to monotherapy.

The development of a robust, predictive biomarker remains a major unmet need and is viewed by many in the field—including Matrana—as the “Holy Grail” of RCC research. A reliable biomarker could help stratify patients by likelihood of benefit from IO-based regimens vs TKI monotherapy or other strategies, thereby optimizing treatment efficacy while potentially reducing unnecessary toxicity.