Abstract BACKGROUND Belzutifan is a HIF-2ɑ inhibitor approved for the treatment of tumors in von Hippel-Lindau (VHL) syndrome and sporadic metastatic clear cell renal cell carcinoma (spRCC) in the refractory setting. The efficacy and side effects of belzutifan are well-documented from clinical trials, however, real-world data examining the incidence and management of adverse events (AEs) are lacking. Our study aims to describe the AE profiles of belzutifan in spRCC and VHL populations. METHODS A retrospective analysis was conducted at Vanderbilt University Medical Center assessing patients who received belzutifan monotherapy. Primary endpoints were incidence of anemia and hypoxia. Secondary endpoints included time to onset of anemia and hypoxia, as well as management strategies. RESULTS Forty-four patients were identified with either spRCC (n = 22) or VHL syndrome (n = 22). Patients with spRCC were older than VHL patients (median 67 vs 41 years) and had higher rates of chronic kidney disease (36.4% vs 4.5%) and prior nephrectomy (77.3% vs 40.9%). The spRCC patients had a median follow-up time of 3.8 months vs 26.8 months in VHL patients. Any-grade anemia occurred in the majority of spRCC and VHL patients (81% and 95.5%, respectively) with a median time of 25 days in spRCC patients and 77 days in VHL patients. While no patient with VHL experienced grade 3 anemia, 41% of spRCC patients developed grade ≥3 anemia. In spRCC, grade ≥3 hypoxia developed in 54.5% and for VHL patients grade 3 hypoxia occurred in 9%. Median time to grade ≥3 hypoxia was 29 days (range 12-123) in spRCC patients and 225 days (105-345) in VHL patients. Supplemental oxygen was required in 52.5% of spRCC patients and 9.5% in VHL patients. Treatment discontinuation due to AEs occurred in 50% of spRCC patients and 13.6% of VHL patients. CONCLUSIONS The time to onset and severity of belzutifan AEs may differ between patients with VHL syndrome and spRCC. These findings suggest the need for a patient-centered approach to monitor and manage toxicity based on disease setting.
Winer et al. (Mon,) studied this question.