A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.

Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy

Background/Aim. First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab. Patients and methods. This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months. Results. Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies. Conclusion. Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors (AU)

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Aptitudes de aprendizaje y desempeño escolar en niños y jóvenes con epilepsia ausencia / Learning skills and academic performance in children and adolescents with absence epilepsy

Introducción: Aunque se describen desórdenes cognitivos y trastornos del aprendizaje en pacientes que presentan epilepsia, son pocos los trabajos que estudian trastornos específicos como la epilepsia ausencia. El objetivo del presente trabajo fue evaluar las características escolares y las aptitudes del aprendizaje en niños y jóvenes que presentan epilepsia ausencia. Métodos: Investigación observacional analítica de casos y controles. Los casos fueron escogidos en la consulta de la Liga Central contra la Epilepsia de Bogotá. Los controles se seleccionaron de un colegio privado y fueron pareados con los casos por edad, grado escolar y sexo. Se evaluaron la historia clínica, la frecuencia de las crisis, el tratamiento farmacológico, el desempeño académico. Las aptitudes escolares se estudiaron por medio de la Batería de Aptitudes Diferenciales y Generales (BADyG). Los datos fueron analizados por medio del test T de Student. Resultados: La muestra estuvo conformada por 19 casos y 19 controles entre los 7 y 16 años. Quince pacientes se encontraban controlados, todos habían recibido medicación antiepiléptica y el 78,9% se encontraba con tratamiento activo. Aunque los casos presentaron mayores fallas académicas, más incidencia en pérdidas de grado y mayores intervenciones terapéuticas que los controles, no hubo diferencias significativas. Igualmente no hubo diferencias en la prueba de BADyG, salvo en la subprueba de memoria inmediata en la que los casos tuvieron resultados superiores (p = 0,0006). Conclusión: Los niños con epilepsia ausencia tratados farmacológicamente y controlados en lo que se refiere a crisis tienen las aptitudes y competencias académicas que corresponden normalmente a su edad

Introduction: Although cognitive and learning disorders have been described in patients with epilepsy, very few studies focus on specific disorders such as absence epilepsy. The aim of this study was to evaluate learning skills and academic performance in children and adolescents with absence epilepsy. Methods: Observational case-control study. Cases were chosen from the Central League against Epilepsy's clinic in Bogotá, Colombia. Controls were selected from a private school and matched with cases by age, school year, and sex. Medical history, seizure frequency, antiepileptic treatment, and academic performance were assessed. Academic abilities were tested with Batería de Aptitudes Diferenciales y Generales (BADyG) (a Spanish-language test of differential and general aptitudes). Data were analysed using Student t-test. Results: The sample consisted of 19 cases and 19 controls aged between 7 and 16. In 15 patients, seizures were controlled; all patients had received antiepileptic medication at some point and 78.9% were actively being treated. Although cases had higher rates of academic failure, a greater incidence of grade retention, and more therapeutic interventions than controls, these differences were not significant. Similarly, there were no significant differences on the BADyG test, except for the immediate memory subcategory on which cases scored higher than controls (P = .0006). Conclusion: Children treated pharmacologically for absence epilepsy, whose seizures are controlled, have normal academic abilities and skills for their age

Cisplatin puls oral vinorelbine as first-line treatment for advanced non-small-cell lung cancer: a prospective study confirming that the day-8 hemogram is unnecessary

INTRODUCTION: Cisplatin plus oral vinorelbine, one of the standard treatments for metastatic non-small-cell lung cancer (NSCLC), is associated with a high rate of neutropenia, and a hemogram is performed on day 8. We analyzed the oncologists' opinions and the result of the hemogram on day 8 to address the question of whether this hemogram could be avoided. MATERIALS AND METHODS: Fifty-eight chemotherapy-naive, advanced NSCLC patients were included. Each received intravenous doses of 75 mg/m(2) cisplatin on day 1 plus oral vinorelbine [60 mg/m(2) in the first cycle (80 mg/m(2) in subsequent cycles) on days 1 and 8], every 3 weeks, for a maximum of six cycles. RESULTS: Out of 257 cycles analyzed, oral vinorelbine was administered on day 8 in 214 (83.2 %) and the dose was canceled in 6 cycles (2.3 %) due to hematological toxicity. On analyzing the patients to whom chemotherapy had been administered on day 8, based on medical opinion without the doctor knowing the hemogram result, we found that the cycle had been administered with a hemogram showing fewer than 1,500 × 10(6) neutrophils in only 3 of the 185 evaluable cycles [event rate of 1.6 %, with confidence interval 95 % = (0.34-4.67 %)]. CONCLUSION: The hemogram on day 8 can be avoided and oral vinorelbine administered in relative safety in patients with good performance status, when confirmed by the clinician's perception, thereby making this regimen more comfortable for the patient. This is the first prospective study to examine this issue (AU)