2023 World Conference on Lung Cancer (Posters)-EP12.02. Frequency and Outcomes of Leptomeningeal Metastases in Patients with Fusion-Positive Lung Cancers

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Researchers from MSKCC in New York conducted a study to investigate the frequency and outcomes of leptomeningeal metastases (LM) in patients with fusion-positive lung cancers. Data was collected from adult patients with fusion-positive lung cancers identified between January 2014 and March 2023 using a DNA-based hybrid capture tumor next generation sequencing (NGS) platform. The incidence of LM in fusion lung cancers was found to be 9%, with the highest frequencies observed in ROS1 and NTRK fusions. LM did not occur in other fusion non-small cell lung cancers (NSCLC). Most patients with LM also had parenchymal brain metastases.<br /><br />The median time to development of LM from the diagnosis of metastatic disease varied depending on the driver mutation, ranging from 7 months in ROS1-positive patients to 36 months in ALK-positive patients. The overall survival after LM diagnosis also varied, with ALK-positive patients having a median survival of 30 months, ROS1-positive patients 13 months, and RET-positive patients 8 months.<br /><br />The most commonly used tyrosine kinase inhibitors (TKIs) to treat LM were lorlatinib, alectinib, and selpercatinib. The median time on TKI after developing LM was 8 months for ALK-positive patients, 3 months for RET-positive patients, and 2 months for ROS1-positive patients.<br /><br />Some patients showed improvement with a switch to another targeted therapy and proton craniospinal irradiation. Whole brain radiation and VP shunts were also used as treatment modalities. The median survival after whole brain radiation was 6 months, and after proton craniospinal irradiation was 8 months.<br /><br />Concomitant alterations were observed in ALK, ROS1, and RET fusions, including mutations in TP53 and CDKN2A/CDKN2B deletions.<br /><br />In conclusion, LM was found in 8% of patients with fusion-positive lung cancers, most commonly occurring on treatment. Responses to treatment were observed with a switch to another targeted therapy and proton craniospinal irradiation. Multidisciplinary care is important for optimal management of LM.<br /><br />Keywords: leptomeningeal metastases, brain metastases, fusion

Asset Subtitle

Monica Chen

Meta Tag

Speaker Monica Chen

Topic Metastatic NSCLC: Targeted Therapy - FUSIONS

Keywords

leptomeningeal metastases

brain metastases

fusion-positive lung cancers

ROS1 fusions

NTRK fusions

non-small cell lung cancers

tyrosine kinase inhibitors

lorlatinib

alectinib

selpercatinib