Abstract 4118: Brain metastases (BM) and next-generation sequencing (NGS) timing: Real-world (RW) outcomes for patients (pts) with advanced non-small cell lung cancer (aNSCLC) and MET exon 14 skipping mutations (METex14)
Authors: Le Xiuning , Robb Stephen , Caro Nydia , Doria Simona , Rhodes Whitney C. , Wu Wen-Hsing , Kim Julia , Prêtre Vincent , Ye Fen 
Published: June 2022

Background: Treatment (Tx) options for METex14 NSCLC have been limited to chemotherapy (Ctx), immunotherapy (IO), and multikinase inhibitors (MKi) until FDA approvals of selective MET inhibitors (METi) from 2020. BM are a further challenge to treat. We previously reported NGS timing in relation to start of first-line Tx (1L) for pts with METex14 NSCLC in the RW. Here we provide overall survival (OS) data, including subgroup analyses for pts with known BM prior to 1L initiation.

Methods: Data originating from ~280 US cancer clinics (~800 sites of care) from the US electronic health record-derived de-identified Flatiron Health Foundation Medicine clinico-genomic database (FH-FMI CGDB) were evaluated. Pts were ≥18 yrs, diagnosed with advanced/metastatic NSCLC from Jan 1, 2011, with NGS-confirmed METex14, ≥1 line of Tx, and ≥90 days follow-up from 1L initiation to cutoff date (Dec 2020). Pts treated with capmatinib or tepotinib were excluded. We examined Tx patterns and OS for pts with and without known BM before starting 1L, and OS for pts with an NGS report before or on/after 1L initiation (time from 1L initiation to death or censoring, analyzed using Kaplan-Meier method with left truncation adjustment to mitigate bias due to the prerequisite for NGS testing). HRs were estimated using Cox regression models with covariates adjustment to estimate risk of death.

Results: The analysis included 156 METex14 NSCLC pts: median age 75 yrs, 59% females, 85.3% non-squamous (NSQ), 9% squamous cell carcinoma (SQ), and 64% had history of smoking. A total of 31 pts (20%) had BM before 1L initiation: median age 73 yrs, 61% females, 94% NSQ, 0% SQ, and 71% had history of smoking. Overall, treatment patterns were similar for pts with and without known BM before 1L initiation (Ctx with or without IO, IO monotherapy, and MKi were all used in 1L). Median OS for pts with BM was 8.11 mo (95% CI, 6.0-19.8) and 14.39 mo (11.1-22.1) for pts without BM, corresponding to a 73% increase in risk of death for pts with BM vs pts without BM by univariate analysis (HR 1.73 [95% CI, 1.06-2.82]; P=0.03). Median OS for pts with an NGS report before and on/after 1L initiation was 13.3 mo (8.8-26.2) and 6.8 mo (0.03-19.8), respectively (P=0.45); HR by multivariate analysis was 0.78 (0.45-1.35) when comparing pts with NGS report before vs on/after 1L initiation.

Conclusions: Tx patterns in 1L were similar for pts with or without BM at time of 1L initiation; presence of BM prior to 1L was associated with inferior outcomes. Numerically longer OS was observed in pts with NGS report prior to 1L initiation vs pts with NGS report on/after 1L, supporting further investigation of underlying causes. These data underline the ongoing unmet clinical need of METex14 NSCLC BM and the importance of investigating upfront comprehensive genomic testing in NSCLC.

Citation Format: Xiuning Le, Stephen Robb, Nydia Caro, Simona Doria, Whitney C. Rhodes, Wen-Hsing Wu, Julia Kim, Vincent Prêtre, Fen Ye. Brain metastases (BM) and next-generation sequencing (NGS) timing: Real-world (RW) outcomes for patients (pts) with advanced non-small cell lung cancer (aNSCLC) and MET exon 14 skipping mutations (METex14) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4118.