Real-world data of osimertinib in the management of leptomeningeal metastases in EGFR mutant NSCLC: Light at the end of the tunnel?

Abstract

e21197 Background: Presence of leptomeningeal metastases (LM) in NSCLC is indicative of aggressive disease and the incidence is as high as 9%-16% in the EGFR mutant subgroup. Traditionally, these patients had a dismal outcome with WBRT and intrathecal chemotherapy. Osimertinib crosses the blood brain barrier and is efficacious in the second line setting, as seen in BLOOM trial (LM ORR of 62%) and AURA program (LM ORR 55%). Osimertinib has also demonstrated CNS efficacy in the first line (FLAURA trial). This study is a retrospective review of cases with LM treated with osimertinib, and their response outcomes. Methods: 16 patients of EGFR mutant NSCLC developed LM at some point in their disease course and were treated with osimertinib. Clinical features and response outcomes were retrieved from medical record archives. Descriptive statistics were done using SPSS v23 software. LM PFS was defined as the time between 1st dose of osimertinib and date of progression in LM. LM OS was defined as the time between the first dose of osimertinib to the date of last follow up/death. ORR was defined as the percentage of cases showing CR/PR to osimertinib. Results: Median age was 61 years (range: 33-79) with 9 males and 7 females. Del19 mutations were seen in 9 patients and L858R in 7 patients. Only one patient was given WBRT prior to TKI. 6 patients with LM at diagnosis were given 1st line osimertinib. 3 (50%) progressed in LM and 3 (50%) showed partial response. Median LM PFS and median LM OS was not reached. ORR for osimertinib in the first line was 83.3%. 10 patients developed LM later in the course of the disease and median time to onset of LM was 12.47 months. Median LM PFS for osimertinib was 7.9 months (95% CI:3.2-8.3). Median LM OS was 8.2 months (95% CI: 2.6-19.8 months). ORR for osimertinib in the later line was 60%. Conclusions: This early experience reveals superior efficacy of osimertinib in LM with an excellent LM ORR in the first line setting and concordant results with second line BLOOM Study. Despite the small numbers in this study, this report becomes clinically relevant owing to the rarity of LM occurrence and paucity of available data. Efficacy of osimertinib in EGFR treatment-naive patients with LM requires further investigation and a larger prospective trial with a longer follow up may help confirm our preliminary findings.