Abstract 145P
Background
IO ± chemotherapy (CT) is first-line therapy for mNSCLC without actionable mutations. We aimed to identify a genomic signature potentially predicting resistance to IO using NGS.
Methods
Pts with mNSCLC who received IO or CT/IO were eligible. NGS was performed by TSO500HT® assay (DNA [522 genes], RNA [55 genes], Tumor Mutational Burden, Microsatellite Instability) or Oncomine Focus Assay® (DNA, 35 genes) plus Archer’s FusionPlex Lung Panel® (RNA, 17 genes), according to quality/quantity cellularity. A least absolute shrinkage and selection operator (LASSO) Cox regression was conducted to choose genes. The correlation between LASSO-selected genes and progression-free survival (PFS) was evaluated by univariable Cox regression. A risk score was derived using regression coefficients of significant genes in the multivariable analysis. Pts were divided into two groups based on the median risk score (0 vs >0). The risk score was evaluated in a multivariable model including clinical features.
Results
56 pts were retrospectively included. 32 (57%) received CT/IO and 23 (43%) IO. Median follow-up was 10.4 months. Among 346 genes, 15 resulted potentially predictive of PFS. At univariable analysis, 6 genes were significantly correlated to PFS: AKT3 (HR 40.39, 95% IC 5.58-292.30, p<0.001), ARID5B (HR 4.98, 95% IC 1.11-22.24, p=0.04), CD276 (HR 14.33, 95% IC 2.60-78.99, p=0.002), PAX8 (HR 8.33, 95% IC 1.78-38.95, p=0.007), PDGFRB (HR 4.88, 95% IC 1.42-16.75, p=0.01) and RICTOR (HR 3.82, 95% IC 1.08-13.57, p=0.04). In the multivariable analysis PAX8 was excluded and a genomic signature with 5 genes was considered. PFS was significantly different in the two risk groups: HR 13.56, 95% IC 5.30-34.67, p<0.001, with a median PFS of 1.64 (95% IC 0.76-NA) vs 13.25 months. (95% IC 10.88-NA). The genomic signature remained prognostic in a multivariable model including age, smoke, histology and regimen (HR 15.71; 95% IC 5.19-47.52, p<0.001).
Conclusions
A genomic signature including AKT3, ARID5B, CD276, PDGFRB and RICTOR alterations was significantly associated with shorter PFS in pts receiving IO. Validation in external cohort is ongoing.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
Medical Oncology Unit, Fondazione Policlinico Agosto Gemelli.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
103P - MSI detection by NGS using tumor samples and liquid biopsy for patients with solid tumors: A single institution experience
Presenter: Alexandra Lebedeva
Session: Cocktail & Poster Display session
Resources:
Abstract
104P - Hypomethylated immune gene promoters as potential biomarkers in oral and oropharyngeal cancer
Presenter: Petra Anić
Session: Cocktail & Poster Display session
Resources:
Abstract
105P - Implementation of technical improvements in cfMeDIP-Seq library preparation
Presenter: Martina Dameri
Session: Cocktail & Poster Display session
Resources:
Abstract
106P - Clinical application of next-generation sequencing in metastatic colorectal cancer (mCRC): Experience from a comprehensive cancer centre
Presenter: David Lluís Garulo
Session: Cocktail & Poster Display session
Resources:
Abstract
107P - Unveiling mismatch repair deficiency (dMMR) and microsatellite-instability high (MSI-H) detection in cancer patients (pt) using a next-generation sequencing (NGS)-based molecular pre-screening program (MPP)
Presenter: Lucia Notario Rincon
Session: Cocktail & Poster Display session
Resources:
Abstract
108P - Validation and implementation of a large NGS panel to test liquid biopsies from patients with suspected advanced non-small cell lung cancer (NSCLC) in an NHS genomic laboratory for the QuicDNA biomarker study
Presenter: Rachel Dodds
Session: Cocktail & Poster Display session
Resources:
Abstract
109P - A multiomic, single-cell measurable residual disease (scMRD) assay for phasing DNA mutations and surface immunophenotypes
Presenter: Simone Formisano
Session: Cocktail & Poster Display session
Resources:
Abstract
110P - Multicellular three-dimensional tumor spheroid of nasopharyngeal carcinoma
Presenter: Shiau Chuen Cheah
Session: Cocktail & Poster Display session
Resources:
Abstract
111P - Development of digital PCR for accurate measurement of HER2 amplification in 184 gastric cancer patients
Presenter: So Young Kang
Session: Cocktail & Poster Display session
Resources:
Abstract
112P - A novel methylation-sensitive assay for early detection of hepatocellular carcinoma to improve surveillance
Presenter: Jeong Sil Ha
Session: Cocktail & Poster Display session
Resources:
Abstract