RESUMO
BACKGROUND: Lenvatinib is approved as a first-line treatment for patients with unresectable and/or recurrent hepatocellular carcinoma (HCC). Lenvatinib achieved promising clinical benefits in REFLECT but was associated with clinically significant treatment-emergent hypertension (CSTE-HTN, a grouped term), a common class effect of tyrosine kinase inhibitors. This post hoc analysis assessed the impact of CSTE-HTN on the efficacy and safety of lenvatinib in HCC. METHODS: Patients from REFLECT who received lenvatinib (n = 476) were stratified according to CSTE-HTN. Tumors were assessed by mRECIST. Overall survival (OS) and progression-free survival (PFS) were evaluated using landmark analyses at 4 and 8 weeks. RESULTS: A total of 212 patients in the lenvatinib arm developed CSTE-HTN, and 264 did not. CSTE-HTN first occurred at 3.7 weeks (median); the worst grade CSTE-HTN occurred at 4.1 weeks (median). No patients had life-threatening CSTE-HTN and/or died due to CSTE-HTN. Median OS was numerically longer in patients with versus without CSTE-HTN (at 4 weeks: 16.3 vs. 11.6 months; hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.621-1.004; at 8 weeks: 13.5 vs. 11.6 months; HR, 0.87; 95% CI, 0.696-1.089). Median PFS was similar between patients with and without CSTE-HTN (at 4 weeks: 6.6 vs. 6.4 months; HR, 0.887; 95% CI, 0.680-1.157; at 8 weeks: 5.7 vs. 6.4 months; HR, 1.09; 95% CI, 0.84-1.41). Objective response rate was numerically higher in patients with (48.6%) versus without CSTE-HTN (34.5%). CONCLUSIONS: In this retrospective analysis, CSTE-HTN was associated with improved OS but not PFS. CSTE-HTN did not impair the outcomes of patients with HCC treated with lenvatinib when detected early and managed appropriately.
Assuntos
Carcinoma Hepatocelular , Hipertensão , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Hepáticas/tratamento farmacológico , Hipertensão/induzido quimicamente , Hipertensão/complicações , Hipertensão/tratamento farmacológicoRESUMO
STUDY OBJECTIVES: Observational data suggest pediatric intensive care unit-related sleep and circadian disruption (PICU-SCD) affects many critically ill children. Multicenter trials exploring PICU-SCD have been impractical because measuring sleep in this setting is challenging. This study validates a questionnaire for caregivers to describe children's sleep in the PICU. METHODS: This prospective, multicenter, case-control study enrolled caregivers of children in 4 PICUs or in a hospital-based sleep laboratory (controls). Survey items were compiled from validated adult ICU and pediatric in- and outpatient sleep questionnaires. Control responses were compared to polysomnography to determine accuracy. A score was calculated by summing the level of disruption of sleep timing, duration, efficiency, quality, and daytime sleepiness and irritability. RESULTS: In responses from 152 PICU and 61 sleep laboratory caregivers, sleep survey items had acceptable internal reliability (α = 0.75) and reproducibility on retest surveys (interclass correlation coefficient > 0.600). Caregivers could not assess sleep of sedated children. Factor analysis identified 3 subscales of PICU-SCD. Control parents had good agreement with polysomnography sleep onset time (κ = 0.823) and sleep onset latency (κ = 0.707). There was a strong correlation between sleep scores derived by parental reporting to those by polysomnography (r = .844, P < .001). Scores had a linear association with caregiver-reported child sleep quality. There were no site-specific differences in sleep quality. Nearly all respondents found the survey easy to understand and of appropriate length. CONCLUSIONS: The Survey of Sleep Quality in the Pediatric Intensive Care Unit provides a reliable, accurate description of inpatient sleep disruption in nonsedated children, generalizable across PICUs. It offers practical means to quantify PICU-SCD daily in future investigations. CITATION: Hassinger AB, Mody K, Gomez R, et al. Validation of the Survey of Sleep Quality in the Pediatric Intensive Care Unit (SSqPICU). J Clin Sleep Med. 2024;20(8):1251-1258.
Assuntos
Unidades de Terapia Intensiva Pediátrica , Qualidade do Sono , Humanos , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Masculino , Feminino , Estudos Prospectivos , Inquéritos e Questionários/normas , Reprodutibilidade dos Testes , Criança , Estudos de Casos e Controles , Pré-Escolar , Polissonografia/métodos , Polissonografia/estatística & dados numéricos , Cuidadores/estatística & dados numéricos , Adolescente , LactenteRESUMO
Introduction: Lenvatinib (dosing for patients who weigh ≥60 kg was 12 mg/day; for patients who weigh <60 kg, the dose was 8 mg/day) plus pembrolizumab 200 mg once every 3 weeks demonstrated antitumor activity and a manageable safety profile in patients with first-line unresectable hepatocellular carcinoma (uHCC) in the open-label phase 1b Study 116/KEYNOTE-524 (primary analysis data cutoff date: October 31, 2019; median follow-up: 10.6 months). This analysis (updated data cutoff date: March 31, 2021) reports efficacy results from 17 months of additional follow-up time. Methods: 100 patients with uHCC were included in the primary analysis (median follow-up: 27.6 months). Endpoints included overall survival (OS), investigator-assessed progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) per modified RECIST. Landmark analyses of OS by the best response at 3 and 9 months were performed. Pembrolizumab antidrug antibodies (ADAs) and concentrations were also measured (cutoff date: August 7, 2020). Results: ORR was 43.0% (95% CI 33.1-53.3%) and median DOR was 17.1 months (95% CI 6.9-19.3 months). Median PFS and OS were 9.3 months (95% CI 7.4-9.8 months) and 20.4 months (95% CI 14.4-25.9 months), respectively. No treatment-emergent ADAs were detected. Conclusion: Results show a sustained treatment effect with lenvatinib plus pembrolizumab in patients with uHCC in the first-line setting.