Search

Introduction: This multicenter review evaluated the efficacy and safety of osimertinib dose escalation for central nervous system (CNS) progression developing on osimertinib 80 mg in EGFR-mutant NSCLC. Methods: Retrospective review identified 105 patients from eight institutions with advanced EGFR-mutant NSCLC treated with osimertinib 160 mg daily between October 2013 and January 2020. Radiographic responses were clinically assessed, and Kaplan-Meier analyses were used. We defined CNS disease control as the interval from osimertinib 160 mg initiation to CNS progression or discontinuation of osimertinib 160 mg. Results: Among 105 patients treated with osimertinib 160 mg, 69 were escalated for CNS progression, including 24 treated with dose escalation alone (cohort A), 34 who received dose-escalated osimertinib plus concurrent chemotherapy and/or radiation (cohort B), and 11 who received osimertinib 160 mg without any prior 80 mg exposure. The median duration of CNS control was 3.8 months (95% confidence interval [CI], 1.7–5.8) in cohort A, 5.1 months (95% CI, 3.1–6.5) in cohort B, and 4.2 months (95% CI 1.6–not reached) in cohort C. Across all cohorts, the median duration of CNS control was 6.0 months (95% CI, 5.1–9.0) in isolated leptomeningeal progression (n = 27) and 3.3 months (95% CI, 1.0–3.1) among those with parenchymal-only metastases (n = 23). Patients on osimertinib 160 mg experienced no severe or unexpected side effects. Conclusion: Among patients with EGFR-mutant NSCLC experiencing CNS progression on osimertinib 80 mg daily, dose escalation to 160 mg provided modest benefit with CNS control lasting approximately 3 to 6 months and seemed more effective in patients with isolated leptomeningeal CNS progression.

Purpose: To evaluate the rate and risk factors of isolated leptomeningeal progression in sinonasal carcinomas. Methods: We retrospectively reviewed imaging and clinical records to determine progression patterns, and estimated rates using the Kaplan‐Meier method. We evaluated risk factors using proportional hazard regression. Results: We analyzed 120 patients who received adjuvant or primary radiotherapy for sinonasal carcinomas. Most patients had T4 disease (68%) and underwent surgery (84%) and chemotherapy (72%). Twenty‐seven (23%) patients developed distant metastases (DM), including 20 (17%) with isolated DMs. Leptomeningeal progression was the most common site of isolated DMs (n = 9; 45%) with an average disease‐free interval of 1.2 years (0.1‐4.3 years). High‐grade histology (P = 0.0003), intracranial invasion (P < 0.0001), and neuroendocrine histology (P = 0.06) were associated with increased risk. Conclusions: Isolated leptomeningeal progression is a common pattern of DM in advanced sinonasal carcinomas. We recommend adding cerebrospinal fluid cytology and contrast‐enhanced spine MRI to routine staging evaluations for high‐risk patients. [ABSTRACT FROM AUTHOR]