2023 Targeted Therapies of Lung Cancer Meeting (Poster)-P1.30. NRG1 Fusions in Non-Small Cell Lung Cancer (NSCLC)

Pdf Summary

NRG1 fusions are rare but actionable genomic events that occur in non-small cell lung cancer (NSCLC) and other tumor types. NRG1 has a domain that activates ErbB receptors, especially HER3, leading to downstream signaling pathways. Agents targeting the HER2/HER3 pathway have shown promise in NRG1 fusion-positive cancers, and Zenocutuzumab has received FDA Fast Track Designation for these tumors. The incidence and characterization of NRG1 fusion-positive NSCLC were updated in this study.<br /><br />The study found that NRG1 fusions in NSCLC are rare but have striking heterogeneity. There were 27 unique fusion partners identified, with the most common being CD74, SLC3A2, and SDC4. Co-mutations were also observed, with TP53 being the most common.<br /><br />PD-L1 expression and tumor mutational burden (TMB) were analyzed in NRG1 fusion-positive NSCLC. Only a small percentage of these tumors had PD-L1 expression of 1% or higher, and even fewer had high TMB. This suggests that immunotherapy targeting PD-L1 or high TMB may not be effective in NRG1 fusion-positive NSCLC.<br /><br />Overall, NRG1 fusions are actionable events in NSCLC, but there is considerable heterogeneity within this alteration. The clinical impact of this heterogeneity on response to targeted agents needs further investigation. The study provides important insights into the characteristics and prevalence of NRG1 fusions in NSCLC, which can guide future research and treatment strategies for patients with these genomic alterations.

Asset Subtitle

Muneeb Rehman, Georgetown University, United States

Meta Tag

Speaker Muneeb Rehman, Georgetown University, United States

Topic Poster Listing

Keywords

NRG1 fusions

non-small cell lung cancer

NSCLC

genomic events

ErbB receptors

fusion partners

PD-L1 expression

tumor mutational burden

immunotherapy

heterogeneity