Tivozanib, a highly potent and selective inhibitor of VEGF receptor tyrosine kinases, for the treatment of metastatic renal cell carcinoma.

The VHL mutation-HIF upregulation-VEGF transcription sequence is the principal pathway in the development of renal cell carcinoma. Tyrosine kinase inhibitors target the VEGF receptors to inhibit further growth of renal cell carcinoma tumors. Tivozanib, originally named AV-951 and KRN-951, is a novel, orally bioavailable VEGF tyrosine kinase inhibitor that is selective for VEGF receptors 1, 2 and 3. Further, only picomolar concentrations of tivozanib are required to target these VEGF receptors and prevent phosphorylation; this potency prevents the debilitating side effects that occur with treatments whose mechanisms of action involve broad-spectrum tyrosine kinase inhibition. This review summarizes the growing body of evidence supporting tivozanib's efficacy and safety in the treatment of advanced renal cell carcinoma.

Identification of High-Incidence Populations in the United States for anti-Epstein Barr Virus Serologic Screening for Nasopharyngeal Carcinoma.

BACKGROUND: In the United States (US), Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) disproportionately impacts Asian Americans (AA) and Native Hawaiians and other Pacific Islanders (NHPI) who have no access to screening. EBV-based screening trials in Asia have detected most cases at early stages. We sought to identify a US target population for NPC screening and hypothesized that once-lifetime screening could be cost-effective. METHODS: We obtained NPC incidence data from the SEER Asian and Pacific Islander datasets. We estimated the number needed to screen, mortality reduction, and resource utilization using a validated model and performance data from trials. Six evaluated strategies incorporated serology, nasopharyngeal swab PCR, and endoscopy or MRI. RESULTS: Intermediate-incidence and high-incidence populations accounted for 10.7% of US person-years yet 42.7% of cases. Anti-BNLF2b screening with selective endoscopy was the preferred strategy. In high-incidence populations, the median NNS to detect one case was 1,992, with a median of 7.12 NPC deaths averted per 100,000 screened. Screening met the willingness-to-pay threshold in all five high-incidence populations (median ICER/GDP 0.82) and among men in intermediate-incidence populations. CONCLUSIONS: Nearly half of NPC in the US arises among the 10% with AA or NHPI ethnicity. A suitable target population for US screening trials would be men and women age 35-65 of Chinese, Samoan, or Southeast Asian ethnicity, or men age 35-60 of Guamanian/Chamorro, Filipino, or Native Hawaiian ethnicity. Once-lifetime anti-BNLF2b screening could be cost-effective. IMPACT: These data may aid the design of US screening trials. Targeted NPC screening might mitigate health disparities.

Bowel perforation in morbid obesity secondary to COVID-19 infection.

The pathophysiology of SARS-CoV-2 is unique in the different pathways the virus utilizes to induce severe systemic inflammation, leading to a higher potential for critical care requirements and a poorer prognosis. Although there are several risk factors for the development of severe infection, one associated with poorer outcome is obesity. In this report, we present a case of bowel perforation in an obese patient with severe COVID-19 infection.

The implementation of lenvatinib/everolimus or lenvatinib/pembrolizumab combinations in the treatment of metastatic renal cell carcinoma.

Introduction: There are 400,000 new cases of Renal Cell Carcinoma (RCC) and 175,000 deaths worldwide every year. Currently available frontline therapies to treat RCC have less toxicity than previously employed therapeutic agents, but drug resistance is still a clinically significant problem. Drug resistance occurs through angiogenic escape by the activation of pathways that are independent of the VEGF targets of most first-line therapies. The lenvatinib/everolimus and lenvatinib/pembrolizumab are part of a new generation of combinations that can combat this method of resistance to extend both progression-free survival and overall survival in patients with metastatic RCC.Areas covered: This article discusses the evolution of current data on the efficacy and safety of these two combinations and future directions for their implementation in the treatment of advanced renal cell carcinoma.Expert opinion: Future research will focus on these combinations in contrast with other currently approved regimens. Once specific biomarkers that predict response to treatment are identified, the future of treatment of mRCC will involve specifically tailored therapies for a patient's genotype. Therapies unique only to the patient undergoing treatment will increase both efficacy and safety of new treatments, and that is the truly exciting future that awaits this field.