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
30P - Role of microRNA and CDKN2A/p16INK4a expression in the prognostication of oral squamous cell carcinoma
Presenter: Olha Burtyn
Session: Cocktail & Poster Display session
Resources:
Abstract
31P - Identification of proteins associated with mRNA processing and maturation by quantitative proteomic analysis in Indian cervical cancer patients
Presenter: Amrita Mukherjee
Session: Cocktail & Poster Display session
Resources:
Abstract
32P - Expression of STAT3 and hypoxia markers in repeatedly resected glioma patients
Presenter: Katerina Dvorakova
Session: Cocktail & Poster Display session
Resources:
Abstract
33P - Unraveling the mechanisms of cisplatin resistance in bladder organoid by single cell RNA sequencing
Presenter: Tingting Xie
Session: Cocktail & Poster Display session
Resources:
Abstract
34P - Functional diagnostics and ex-vivo screening of erlotinib and nintedanib in non-small cell lung carcinoma: Implications for multidrug resistance and personalized therapy
Presenter: Jelena Dinić
Session: Cocktail & Poster Display session
Resources:
Abstract
35P - Enhancing efficacy of the MEK inhibitor trametinib in KRAS-mutated colorectal cancer cells
Presenter: Lee Ellis
Session: Cocktail & Poster Display session
Resources:
Abstract
36P - Comparison of pelitinib, tepotinib or docetaxel efficacy according to the copy number or gene alteration status of EGFR, MET, HRAS, KRAS and NRAS genes
Presenter: Dae Young Zang
Session: Cocktail & Poster Display session
Resources:
Abstract
37P - NET-mediated radio-resistance in early-stage non-small cell lung cancer
Presenter: Malcolm Ryan
Session: Cocktail & Poster Display session
Resources:
Abstract
39P - The use of antibiotics or proton pump inhibitors and the response to intravesical Bacillus Calmette Guérin therapy in non-muscle-invasive bladder cancer
Presenter: João Barbosa Martins
Session: Cocktail & Poster Display session
Resources:
Abstract
40P - YAP1 promotes sorafenib resistance by activation of TGFβ signaling pathway
Presenter: Chit Lai Chee
Session: Cocktail & Poster Display session
Resources:
Abstract