ABSTRACT
Background: We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19). Methods: This phase 2b clinical trial enrolled adult patients from 34 hospitals in France. Eligible patients had a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 within 14 days of onset of symptoms that required hospitalization for low-flow oxygen therapy (<6â L/min of oxygen). Patients were randomly assigned to receive a single intravenous infusion of 2â mg/kg of XAV-19 or placebo. The primary end point was the occurrence of death or severe respiratory failure between baseline and day 15. Results: Between January 12, 2021, and April 16, 2021, 398 patients were enrolled in the study and randomly assigned to XAV-19 or placebo. The modified intention-to-treat population comprised 388 participants who received full perfusion of XAV-19 (199 patients) or placebo (189 patients). The mean (SD) age was 59.8 (12.4) years, 249 (64.2%) individuals were men, and the median time (interquartile range) from symptom onset to enrollment was 9 (7-10) days. There was no statistically significant decrease in the cumulative incidence of death or severe respiratory failure through day 15 in the XAV-19 group vs the placebo group (53/199 [26.6%] vs 48/189 [25.4%]; adjusted risk difference, 0.6%; 95% CI, -6% to 7%; hazard ratio, 1.03; 95% CI, 0.64-1.66; P = .90). In the safety population, adverse events were reported in 75.4% of 199 patients in the XAV-19 group and in 76.3% of 190 patients in the placebo group through D29. Conclusions: Among patients hospitalized with COVID-19 requiring low-flow oxygen therapy, treatment with a single intravenous dose of XAV-19, compared with placebo, did not show a significant difference in terms of disease progression at day 15.
ABSTRACT
PURPOSE: Median age for the diagnosis of metastatic bladder cancer (MBC) is 73 years. The feasibility of chemotherapy in older patients is controversial. Our objectives were to assess associations linking age to first line chemotherapy regimen selection, early chemotherapy discontinuation, and 1-year mortality in everyday practice. MATERIALS AND METHODS: Between 1999 and 2011, 197 consecutive patients aged≥70 years with MBC referred to 4 hospitals were included in the AGEVIM multicenter cohort. At baseline, we recorded performance status (PS); tumor characteristics; the Charlson Comorbidity Index; and plasma creatinine, hemoglobin, and albumin. Early discontinuation data were available for 193 patients, and overall 1-year mortality for 180 patients. We assessed the probabilities of initial cisplatin-based combination chemotherapy (CCC), early discontinuation (≤2 cycles), and 1-year mortality, using multivariate logistic regression and Cox proportional hazards modeling. RESULTS: Among the 193 patients (mean age: 76±4.3y), with 2 metastatic site in median 43.5% received CCC, 36.3% gemcitabine and carboplatin, and 20.2% gemcitabine alone. The probability of CCC decreased with age independently from sex, PS, creatinine clearance, and Charlson Comorbidity Index (P<0.0001), early discontinuation occurred in 24.9% of patients. Factors independently associated with global chemotherapy early discontinuation were age (adjusted odds ratioper additional year = 1.11; 95% CI: 1.02-1.20; P = 0.01) and higher metastatic-site number (adjusted odds ratioper additional site = 1.45; 95% CI: 1.08-1.95; P = 0.01). The number of patients was too small for a robust analysis of factors associated with early chemotherapy discontinuation in each chemotherapy regiment subgroup. Independent predictors of 1-year mortality (median = 9.6 mo) were early discontinuation (adjusted hazard ratio [aHR] = 4.77 [2.85-7.96] when PS<2 and 20.6 [9.43-44.82] when PS≥2; P<0.0001), albumin<35g/l (aHR = 3.06 [1.81-5.17], P = 0.0001), creatinine clearance<30ml/min (aHR = 2.96 [1.45-6.06], P = 0.009), and higher metastatic-site number (aHR = 1.34 [1.14-1.56], P<0.0001). CONCLUSION: Less than half of older patients with MBC received initial CCC and 25% had≤2 cycles of chemotherapy. Older age was associated with decreased CCC prescription, independently from known contraindications, and with global chemotherapy early discontinuation, but not with 1-year mortality.
