Sie sind bereits registriert?
Loggen Sie sich mit Ihrem Universimed-Benutzerkonto ein:
Sie sind noch nicht registriert?
Registrieren Sie sich jetzt kostenlos auf universimed.com und erhalten Sie Zugang zu allen Artikeln, bewerten Sie Inhalte und speichern Sie interessante Beiträge in Ihrem persönlichen Bereich zum späteren Lesen. Ihre Registrierung ist für alle Unversimed-Portale gültig. (inkl. allgemeineplus.at & med-Diplom.at)
Novel Treatment for von Hippel–Lindau–Related Clear Cell Renal Cancer
Patients with von Hippel–Lindau (VHL) disease, which is caused by germline pathogenic variations in the VHL gene, have a high incidence of clear cell renal cancer (ccRC) in addition to a myriad of extra-renal manifestations, including hemangioblastomas of the central nervous system (CNS) and pancreatic neuroendocrine tumors. Hypoxia-inducible factor 2α (HIF-2α) is a transcription factor known to drive the progression of ccRC.
Investigators conducted an industry-sponsored multinational phase 2 trial of a novel HIF-2α inhibitor, belzutifan, in patients with VHL-related ccRC. Eligible patients were required to have good ECOG performance status and at least one measurable site of disease. Patients received belzutifan orally at 120 mg daily. The primary endpoint was objective response rate (ORR) assessed by independent review; important secondary endpoints included progression-free survival (PFS) and efficacy of treatment in non–renal cancer neoplasms (e.g., retinal/CNS hemangioblastomas).
Of 61 patients, the median age was 41, and 97% had undergone at least one prior tumor-reduction procedure. At a median follow-up of 21.8 months, the ORR was 49%, with disease control in 98% of patients. At 2 years, PFS was 96%. Efficacy in non-renal neoplasms included confirmed responses in 77% of patients with pancreatic lesions and 30% with CNS hemangioblastomas. Most adverse events were grade 1–2; 90% of patients experienced anemia and 66% fatigue, with 7 patients discontinuing therapy.
As noted by an editorialist, for patients with VHL disease the promising benefit of the FDA's recent approval of belzutifan goes beyond the responses seen in VHL-related ccRC, given the promising activity seen in non-renal neoplasms, which typically occur earlier in the disease course and frequently lead to serious morbidity. Multiple studies of belzutifan as monotherapy and in combination with immune checkpoint inhibitors in advanced ccRC are ongoing.
Jonasch E et al.
Title: Belzutifan for renal cell carcinoma in von Hippel–Lindau disease.
Source: N Engl J Med 2021 Nov 25; [e-pub]. (Abstract/FREE Full Text)