Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer (BLOSSOM).

PURPOSE: Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs. MATERIALS AND METHODS: In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6. RESULTS: A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set-T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2. CONCLUSION: The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.

The safety and efficacy of intra-arterial low-dose tirofiban administration during endovascular therapy in patients with large ischemic core volume.

This study aimed to evaluate the safety and efficacy of intra-arterial (IA) administration of low- dose tirofiban during endovascular therapy in patients with large ischemic core volumes on initial brain CT. Patients were divided into two groups based on the use of IA tirofiban. We identified 87 patients (16 and 71 patients in the tirofiban and no-tirofiban groups, respectively) with acute ischemic stroke due to intracranial artery occlusion who underwent endovascular therapy with a low Alberta Stroke Program Early CT scores (2-5). Multivariate logistic regression analysis revealed no association between IA tirofiban administration and serious postprocedural hemorrhagic complications (adjusted odds ratio (aOR), 0.720; 95% confidence interval (CI) 0.099-5.219; p = 0.960), any radiologic hemorrhage (aOR 0.076; 95% CI 0.003-2.323; p = 0.139), or 3-month mortality (aOR, 0.087; 95% CI 0.005-1.501; p = 0.093). However, IA tirofiban was associated with a lower 90-day mRS score (aOR, 0.197; 95% CI 0.015-1.306; p = 0.017) and change of NIHSS compared with baseline (aOR, 0.698; 95% CI 0.531-0.917; p = 0.010). IA tirofiban administration during endovascular therapy in patients with large ischemic core volumes may be effective and safe.

Factors associated with myopia in 19-year-old adult men in Korea between 2014 and 2020.

Numerous environmental factors that influence myopia have been studied, but only few factors have been definitively identified. We examined factors influencing myopia using data from 2014 to 2020 physical examinations received from the Korean Military Manpower Administration. We used the Cochran-Armitage trend test to investigate the annual prevalence of myopia and high myopia. To determine risk factors for myopia, logistic regression was performed. The data of 2,215,126 19-year-old Korean men were examined. The myopia and high myopia prevalences showed significant annual increases; in 2020, these prevalences were 58.9% and 18.0%, respectively. The myopia prevalence was high when the birth season was spring, education level was high, height was small, weight and body mass index (BMI) were low (< 18.5 kg/m2), and color vision was normal (all, p < 0.05). The high myopia prevalence was high when the birth season was spring, education level was high, height was tall, weight and BMI were low (< 18.5 kg/m2), and color vision was normal (all, p < 0.05). The prevalence of myopia and high myopia in this population is increasing annually. The risk of both conditions increased when the birth season was spring, education level was high, BMI was low, color vision was normal, and diabetes was present.