Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease
| Autor: | Othon Iliopoulos, Rodolfo F. Perini, Vivek Narayan, Jodi K. Maranchie, Sarah J. Welsh, Frede Donskov, Eric Jonasch, Stéphane Oudard, Sanjay Thamake, Benjamin L. Maughan, Mk Investigators, Eric Kristopher Park, Tobias Else, W. Kimryn Rathmell, Ramaprasad Srinivasan, W. Marston Linehan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male von Hippel-Lindau Disease endocrine system diseases VHL Gene Inactivation Antineoplastic Agents Disease urologic and male genital diseases Article Neoplasms Multiple Primary Transcription (biology) Renal cell carcinoma Basic Helix-Loop-Helix Transcription Factors Humans Medicine cardiovascular diseases Age of Onset Von Hippel–Lindau disease Carcinoma Renal Cell neoplasms Fatigue Aged business.industry Incidence (epidemiology) Anemia General Medicine Middle Aged medicine.disease Kidney Neoplasms female genital diseases and pregnancy complications Hemangioblastoma Pancreatic Neoplasms Neuroendocrine Tumors Indenes Von Hippel-Lindau Tumor Suppressor Protein Disease Progression Cancer research Female business Follow-Up Studies |
| Zdroj: | Jonasch, E, Donskov, F, Iliopoulos, O, Rathmell, W K, Narayan, V K, Maughan, B L, Oudard, S, Else, T, Maranchie, J K, Welsh, S J, Thamake, S, Park, E K, Perini, R F, Linehan, W M, Srinivasan, R & the MK-6482-004 Investigators 2021, ' Belzutifan for renal cell carcinoma in von Hippel-Lindau disease ', New England Journal of Medicine, vol. 385, no. 22, pp. 2036-2046 . https://doi.org/10.1056/NEJMoa2103425 N Engl J Med |
| ISSN: | 1533-4406 0028-4793 |
| DOI: | 10.1056/nejmoa2103425 |
| Popis: | BACKGROUND: Patients with von Hippel–Lindau (VHL) disease have a high incidence of renal cell carcinoma owing to VHL gene inactivation and constitutive activation of the transcription factor hypoxia-inducible factor 2α (HIF-2α). METHODS: In this phase 2, open-label, single-group trial, we investigated the efficacy and safety of the HIF-2α inhibitor belzutifan (MK-6482, previously called PT2977), administered orally at a dose of 120 mg daily, in patients with renal cell carcinoma associated with VHL disease. The primary end point was objective response (complete or partial response) as measured according to the Response Evaluation Criteria in Solid Tumors, version 1.1, by an independent central radiology review committee. We also assessed responses to belzutifan in patients with non–renal cell carcinoma neoplasms and the safety of belzutifan. RESULTS: After a median follow-up of 21.8 months (range, 20.2 to 30.1), the percentage of patients with renal cell carcinoma who had an objective response was 49% (95% confidence interval, 36 to 62). Responses were also observed in patients with pancreatic lesions (47 of 61 patients [77%]) and central nervous system hemangioblastomas (15 of 50 patients [30%]). Among the 16 eyes that could be evaluated in 12 patients with retinal hemangioblastomas at baseline, all (100%) were graded as showing improvement. The most common adverse events were anemia (in 90% of the patients) and fatigue (in 66%). Seven patients discontinued treatment: four patients voluntarily discontinued, one discontinued owing to a treatment-related adverse event (grade 1 dizziness), one discontinued because of disease progression as assessed by the investigator, and one patient died (of acute toxic effects of fentanyl). CONCLUSIONS: Belzutifan was associated with predominantly grade 1 and 2 adverse events and showed activity in patients with renal cell carcinomas and non–renal cell carcinoma neoplasms associated with VHL disease. (Funded by Merck Sharp and Dohme and others; MK-6482-004 ClinicalTrials.gov number, NCT03401788.) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|