Dr Rini on the Utility of Belzutifan in RCC

Brian I. Rini, MD, FASCO, Ingram Professor of Medicine, Division of Hematology Oncology, chief, Clinical Trials, Vanderbilt-Ingram University Cancer Center, discusses the background that led to the FDA approval of belzutifan (Welireg) for the treatment of patients with advanced renal cell carcinoma (RCC). 

Belzutifan is a well-tolerated medication, generally associated with better tolerability than most TKIs, Rini begins. Its distinctive adverse effects (AEs) primarily include anemia, which arises due to the inhibition of HIF, a gene responsible for erythropoietin and hemoglobin production, which belzutifan targets, he explains. Fortunately, anemia is relatively easy to manage with growth factors or by temporarily withholding the medication, Rini reports. Unlike anemia induced by other therapies in different diseases, belzutifan-associated anemia is typically straightforward to handle and aligns with the drug’s mechanism of action, he states.

Hypoxia is a rarer occurrence and can usually be managed by adjusting the dosage of belzutifan without requiring additional interventions, Rini expands. This AE is somewhat unique to belzutifan, as hypoxia is not commonly associated with other agents. Overall, belzutifan is generally well tolerated, as evidenced by long-term usage in patients with von Hippel-Lindau syndrome, some of whom have been receiving the medication for several years without significant long-term AEs, he says.

In refractory patient populations, where patients often experience more pronounced symptoms from their disease and may have endured multiple prior treatments, tolerability becomes a crucial factor in treatment selection, Rini elucidates. The approval of belzutifan provides another valuable treatment option in this challenging setting, he explains. Each patient may respond differently to treatments and exhibit varying levels of tolerance, making it essential to tailor treatments to individual needs, according to Rini.

Although identifying the specific patient subsets that benefit most from belzutifan remains an ongoing task, trials in progress, particularly those exploring combination therapies in both the first- and second-line settings, hold promise, he continues. Belzutifan's favorable tolerability profile makes it well suited for combination approaches, and forthcoming data may elucidate its potential in earlier disease stages and in combination regimens, Rini concludes.