BIOM-01. GENOMIC ALTERATIONS IN ALK FUSION-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC) PATIENTS WITH BRAIN METASTASES

Autor: Jordan Eichholz, Emily Miao, Emily Lebow, Henry Walch, Jessica Flynn, Zhigang Zhang, Harper Hubbeling, Kathryn Beal, Nelson Moss, Kenny Yu, Jonathan Yang, Alicia Meng, Daniel Kelly, Thomas Boerner, Daniel Gomez, Andreas Rimner, Nikolaus Schultz, Alexander Drilon, Brandon Imber, Luke Pike
Rok vydání: 2022
Předmět:
Zdroj: Neuro-Oncology. 24:vii3-vii3
ISSN: 1523-5866
1522-8517
Popis: PURPOSE Brain metastases (BM) are common in patients with anaplastic lymphoma kinase fusion-positive NSCLC (ALK+ NSCLC). We characterized the genomics of patients with ALK+ NSCLC BM treated with alectinib with or without local therapy to identify correlations of co-mutations with CNS-specific outcomes. METHODS We retrospectively reviewed ALK+ NSCLC patients with BMs who received alectinib for the definitive treatment of BM from 1/2012 and 5/2021. Genomic characteristics of 27 specimens from 27 patients were assessed with MSK-IMPACT, a 505-gene next-generation sequencing (NGS)-based tumor sequencing assay with >700x coverage. Intracranial progression-free survival (iPFS) and overall survival (OS) from BM diagnosis were analyzed using standard statistical methods. RESULTS The median age at BM diagnosis was 57 years (range 25-83). Median iPFS was 1.94 years (95%CI: 1.58- not reached) and median OS was 6.08 years (95%CI: 1.7– not reached). All patients received alectinib for the treatment of brain metastases (78% as 1st-line TKI) and 22% received local therapy. The most frequently altered co- alterations were CDKN2A (48%), TP53 (22%), MAP2K4 (15%), SMARCA4 (11%), CREBBP (11%), and ATM (7%). CDKN2A alterations were more common in patients with intracranial progression (64% vs 31%). MAP2K4 alterations were enriched in metastatic samples (p = 0.028, q = 0.113). SMARCA4 co- alterations were associated with inferior OS (HR: 8.76, 95%CI = 1.74-44.2, p= 0.009) and trended toward association with iPFS but was insignificant (HR: 3.25, 95%CI = 0.83-12.4, p=0.089). We identified missense ALK alterations in CSF from a patient who acquired resistance to alectinib and had leptomeningeal progression (G1269A, I1171T, L1108P). CONCLUSION This study is the first analysis of CNS specific outcomes with detailed genomic annotation for ALK+ NSCLC patients who received definitive alectinib for BM. Further investigation into the role of CNS-penetrant TKIs and the genomic alterations predictive of CNS failure are needed.
Databáze: OpenAIRE
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