Virtual Library
Start Your Search
Augusto Obuti Saito
Author of
-
+
P33 - Pathology - Immunotherapy Biomarker (ID 101)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P33.19 - Association Between Expression of Immune Response-Related Genes and Response to Nivolumab in Metastatic Non-Small Cell Lung Cancer (ID 3572)
00:00 - 00:00 | Presenting Author(s): Augusto Obuti Saito
- Abstract
Introduction
Immune checkpoints inhibitors (ICIs) have provided long durable responses in many tumor types, including non-small cell lung cancer (NSCLC). Unfortunately, most patients do not benefit from ICI therapy and, eventually, adverse events can be severe. Therefore, biomarkers to identify patients most likely to benefit from immunotherapy are urgently needed.
Methods
To identify a gene expression profile associated with tumor response and clinical outcomes in a cohort of patients with metastatic NSCLC treated with nivolumab in second or further lines of therapy.
Thirty metastatic NSCLC patients treated with nivolumab in second or later lines at A. C. Camargo Cancer Center, São Paulo, Brazil, from 2015 to 2017 were included. Twenty patients have been previously included in an expanded access program of nivolumab (BMS CA 209-169). Baseline (before ICI) archival FFPE samples were obtained and RNA was extracted. The expression of 41 genes involved with immune response (CCL2, CCL3, CCL4, CCL5, CCL19, CCL21, CD274, CD3D, CD3Z, CD8A, CXCL9, CXCL10, CXCL11, CXCL13, CXCR6, EOMES, FOXP3, GZMA, GZMB, HLA-DRA1, HLAE-DRA1, IFNG, IL10, IRF1, IRF3, IRF7, LAG3, MAVS, NKG7, PDCD1, PFR1, PTPRC, RIG1, STAT1, TBET, GATA3, TBX21, TGFB, TIGIT, STING, TNFA) was analyzed by RT-qPCR in a Taq-Man Low-Density Array platform. Demographic data and treatment outcomes were collected retrospectively from medical records. Treatment response was assessed by RECIST 1.1 and patients were categorized as achieving clinical benefit (CB) [complete response (CR), partial response (PR) or stable disease (SD) ≥6 months] or disease progression (DP) [SD <6 months or DP]. Response to treatment was correlated with expression of each isolated gene using the two-sided Wilcoxon test, area under the curve (AUC) and logistic regression. Analyses of overall survival (OS) and progression-free survival (PFS) were performed using Cox regression.
Results
In this cohort, the median age at onset of nivolumab was 58.5 years. Fifteen patients (50%) were male, 80% had good performance status (ECOG 0-1), 63.3% had metastatic disease at diagnosis and 76.6% were smokers or former smokers. Adenocarcinoma was the most common histology (80%), and only 4 patients had a driver mutation detected. Nivolumab was administered as second or third line of treatment in 73% of cases. After a median follow-up of 43 months, the median PFS was 2.2 months (95% CI, 0.0-4.86) and the median OS was 16.4 months (95% CI, 10.6-22.3). The CB rate was 36.7%. Gene expression of CCL3, LAG3, IL10, FOXP3, PTPRC, CCL5, IFNG, NKG7, IRF1 and CXCL9 was associated with CB (p<0.05). Among these genes, we chose that better predicted CB (AUC>0.7) and combined them to generate a gene expression signature. The signature score predicted CB with an AUC of 0.81 (p=0.01). Additionally, patients with a high signature score presented significantly improved PFS (HR 0.11, p=0.0003) and OS (HR 0.30, p=0.029).
Conclusion
In this small cohort of NSCLC patients treated with nivolumab in second or later lines, survival was similar to that previously reported for nivolumab as second line in the literature. We were able to identify a gene expression signature associated with tumor response, PFS and OS.
