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SummaryBackgroundThere are few effective treatments for advanced urothelial carcinoma after progression following platinum-based chemotherapy. We assessed the activity and safety of nivolumab in patients with locally advanced or metastatic urothelial carcinoma who progressed after prior platinum-based therapy.MethodsThis phase 1/2 multicentre open-label study enrolled patients aged ≥18 years with urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra unselected by programmed death ligand-1 (PD-L1). Tumour PD-L1 membrane expression was assessed. Patients received nivolumab 3 mg/kg intravenously every 2 weeks until disease progression or study treatment discontinuation, whichever occurred later. The primary endpoint was objective response rate by investigator assessment. All patients who received at least one dose of any study medication were analysed. Here we report an interim analysis of this ongoing trial. CheckMate 032 is registered with ClinicalTrials.gov, NCT01928394.FindingsBetween June 2014 and April 2015, 86 patients with metastatic urothelial carcinoma were enrolled and 78 were treated with nivolumab monotherapy. At data cutoff (March 24, 2016), minimum follow-up was 9 months. A confirmed investigator-assessed objective response was achieved in 19 (24·4%) of 78 patients (95% CI 15·3–35·4). Grade 3/4 treatment-related adverse events occurred in 17 (21·8%) of 78 patients, the most common being laboratory abnormalities: asymptomatic elevated lipase in four (5·1%) and asymptomatic elevated amylase three (3·8%) patients. Serious adverse events were reported in 36 (46·2%) of 78 patients. Two (2·6%) of 78 patients discontinued due to treatment-related adverse events (pneumonitis and thrombocytopenia) and subsequently died.InterpretationNivolumab monotherapy was associated with significant and durable clinical responses and a manageable safety profile in previously treated patients with locally advanced or metastatic urothelial carcinoma. These data indicate a favourable benefit:risk profile for nivolumab and support further investigation of nivolumab monotherapy in advanced urothelial carcinoma.

Human coronavirus NL63 (HCoV-NL63), one of the main circulating HCoVs worldwide, causes respiratory tract illnesses like runny nose, cough, bronchiolitis and pneumonia. Recently, a severe respiratory illness outbreak of HCoV-NL63 has been reported in a long-term care facility. Sambucus FormosanaNakai, a species of elderberry, is a traditional medicinal herb with anti-inflammatory and antiviral potential. The study investigated the antiviral activity of Sambucus FormosanaNakai stem ethanol extract and some phenolic acid constituents against HCoV-NL63. The extract was less cytotoxic and concentration-dependently increased anti-HCoV-NL63 activities, including cytopathicity, sub-G1 fraction, virus yield (IC50 = 1.17 μg/ml), plaque formation (IC50 = 4.67 μg/ml) and virus attachment (IC50 = 15.75 μg/ml). Among the phenolic acid constituents in Sambucus FormosanaNakai extract, caffeic acid, chlorogenic acid and gallic acid sustained the anti-HCoV-NL63 activity that was ranked in the following order of virus yield reduction: caffeic acid (IC 50 = 3.54 μM) > chlorogenic acid (IC 50 = 43.45 μM) > coumaric acid (IC 50 = 71.48 μM). Caffeic acid significantly inhibited the replication of HCoV-NL63 in a cell-type independent manner, and specifically blocked virus attachment (IC 50 = 8.1 μM). Therefore, the results revealed that Sambucus Formosana Nakai stem ethanol extract displayed the strong anti-HCoV-NL63 potential; caffeic acid could be the vital component with anti-HCoV-NL63 activity. The finding could be helpful for developing antivirals against HCoV-NL63.

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