ABSTRACT
PURPOSE OF REVIEW: To review the biology, drug development, and clinical data regarding the efficacy and safety of belzutifan (MK-6482), a small molecule inhibitor of HIF-2α. RECENT FINDINGS: Belzutifan, a second-generation HIF-2α inhibitor, was shown to provide clinically meaningful benefit in the treatment of VHL-associated tumors (including ccRCC, pancreatic lesions as well as neuroendocrine tumor, and CNS hemangioblastomas). The recommended dose of belzutifan is 120 mg orally daily and half-life is 14 h. In pretreated ccRCC, belzutifan achieved disease control rate of 80% in phase I trial. The most common side effects include anemia and hypoxia related symptoms. Investigation into the important role HIF-2α plays in the expression of genes associated with angiogenesis, erythropoiesis, carcinogenesis, and progression of tumors and the discovery of structural vulnerability within HIF-2α have resulted in the development of a new therapy that has demonstrated efficacy and safety in recent clinical trials. Further research is ongoing to optimize therapeutic benefits from this new exciting therapeutic modality and to improve the outcome of HIF-2α-driven tumors.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/pathology , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/therapeutic use , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Von Hippel-Lindau Tumor Suppressor Protein/metabolism , BiologyABSTRACT
OBJECTIVES: To characterize the frequency and association of gastrointestinal (GI) symptoms with outcomes in patients with corona virus disease 2019 (COVID-19) admitted to the hospital. METHODS: Records were retrospectively collected from patients admitted to a tertiary care center in Washington, D.C., with confirmed COVID-19 from March 15, 2020 to July 15, 2020. After adjusting for clinical demographics and comorbidities, multivariate logistic regression analysis was performed. RESULTS: The most common presenting symptoms of COVID-19 in patients that were admitted to the hospital were cough (38.4%), shortness of breath (37.5%), and fever (34.3%), followed by GI symptoms in 25.9% of patients. The most common GI symptom was diarrhea (12.8%) followed by nausea or vomiting (10.5%), decreased appetite (9.3%), and abdominal pain (3.8%). Patients with diarrhea were more likely to die (odds ratio [OR] 2.750; p = 0.006; confidence interval [CI] 1.329-5.688), be admitted to the intensive care unit (ICU) (OR 2.242; p = 0.019; CI 1.139-4.413), and be intubated (OR 3.155; p = 0.002; CI 1.535-6.487). Additional outcomes analyzed were need for vasopressors, presence of shock, and acute kidney injury. Patients with diarrhea were 2.738 (p = 0.007; CI 1.325-5.658), 2.467 (p = 0.013; CI 1.209-5.035), and 2.694 (p = 0.007; CI 1.305-5.561) times more likely to experience these outcomes, respectively. CONCLUSIONS: Screening questions should be expanded to include common GI symptoms in patients with COVID-19. Health care providers should note whether their patient is presenting with diarrhea due to the potential implications on disease severity and outcomes.
