2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.13E.02 Multi-Omics Analysis of Patients with Extended-Disease Small Cell Lung Cancer Who Received Chemoimmunotherapy: APOLLO-Bio Study.

EP.13E.02 Multi-Omics Analysis of Patients with Extended-Disease Small Cell Lung Cancer Who Received Chemoimmunotherapy: APOLLO-Bio Study.

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The APOLLO-Bio study investigated potential biomarkers for predicting the effectiveness of chemoimmunotherapy (Chemo-IO) in patients with extensive-disease small cell lung cancer (ED-SCLC). Typically, this treatment only extends progression-free survival (PFS) by about a month, prompting the need for enhanced prediction tools. <br /><br />The study was part of the larger APOLLO trial and included 207 participants; data was collected from 137 formalin-fixed, paraffin-embedded specimens. Researchers used next-generation sequencing to analyze DNA and RNA for gene alterations and expressions. Immunohistochemistry targeted proteins ASCL1, NEUROD1, YAP1, and POU2F3 to assess their correlation with treatment outcomes.<br /><br />Key findings included the KMT2D gene mutation, which was linked to poorer effectiveness and higher incidence among non-responders. Additionally, common gene alterations such as TP53 (73%), RB1 (33%), and EPHB4 (25%) were noted. IHC-based subtyping identified NEUROD1 and ASCL1 as the most prevalent, with 48 patients each, followed by POU2F3 (18 patients) and YAP1 (4 patients). Double-negative for NEUROD1 and ASCL1 subtypes exhibited shorter median PFS, although this was not significantly distinct.<br /><br />By clustering based on gene expression, researchers found two differentiated groups, with one cluster containing more double-negative individuals. Gene expression analysis indicated upregulation of immunoglobulin receptor-binding, chemokines, IDO activity, and JAK-STAT signaling pathways in patients with longer PFS. These insights highlight the potential of molecular subtyping for optimizing treatment strategies in ED-SCLC.<br /><br />Overall, the study underscores the necessity for personalized medicine approaches in cancer treatment by utilizing molecular characteristics to identify potential responders to Chemo-IO. This research was supported by Chugai Pharmaceutical Co.

Asset Subtitle

Hiroaki Akamatsu

Meta Tag

Speaker Hiroaki Akamatsu

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

APOLLO-Bio study

biomarkers

chemoimmunotherapy

small cell lung cancer

next-generation sequencing

gene alterations

immunohistochemistry

KMT2D mutation

molecular subtyping

personalized medicine