Osimertinib for patients (pts) with leptomeningeal metastases (LM) associated with EGFRm advanced NSCLC: The AURA LM study

Abstract

Background:LM are associated with debilitating symptoms and poor prognosis.Osimertinib, a third-generation, CNS-active EGFR-TKI selective for both sensitizingand EGFR T790M resistance mutations, has shown efficacy in pts with CNS metastases;encouraging activity has been reported in pts with LM at 160 mg once daily (QD)(BLOOM; NCT02228369). Here we report LM activity with osimertinib 80 mg QD inpts with LM from four studies across the AURA program (NCT01802632;NCT02094261; NCT02442349; NCT02151981).Methods:Pts with T790M-positive advanced NSCLC and prior progression on EGFR-TKI therapy received osimertinib 80 mg QD. Asymptomatic, stable CNS metastases,including LM, were allowed. Baseline brain scans were mandated in pts with known ortreated CNS metastases at study entry; pts with radiologic evidence of LM by neurora-diological blinded independent review (BICR) were included for analysis. Follow-upbrain scans were assessed for radiologic LM response by LM BICR per ResponseAssessment in Neuro-Oncology LM criteria (Chamberlain et al. Neuro Oncol, 2017,19:484). Assessment of brain and/or spine imaging was completed qualitatively.Efficacy endpoints included LM objective response rate (ORR), LM duration ofresponse (DoR), LM progression-free survival (PFS) and overall survival (OS). Resultsare based on the individual data cutoff applied for each study.Results:Of the 22 pts with LM included for analysis, median treatment exposure was7.3 months (mo) (range 2.3–16.5). Baseline characteristics were broadly consistentwith the overall study population: median age 58 yrs; female 59%; Asian 82%; WHO PS1 82%. LM ORR was 55% (95% CI 32, 76), with complete LM response and partial LMresponse reported in 6 pts (27%) each. Median LM DoR for confirmed responders wasnot calculable (range 1.3–11.1 mo). Median LM PFS was 11.1 mo (95% CI 4.6, NC).Based on available survival data, median OS was 18.8 mo (95% CI 6.3, NC).Conclusions:Osimertinib showed a clinically meaningful benefit in pts with T790M-positive NSCLC and radiologically detected LM, suggesting 80 mg QD can be an effec-tive dose for management of LM associated with EGFRm NSCLC. Further study isneeded to evaluate the role of osimertinib 80 mg QD in pts with LM in a real-worldsetting.Editorial acknowledgement:Laura Crocker.Clinical trial identification:AURA extension (NCT01802632), AURA2(NCT02094261), AURA3 (NCT02151981), AURA17 (NCT02442349).Legal entity responsible for the study:AstraZeneca.Funding:AstraZeneca.Disclosure:M-J. Ahn: