Abstract 2975
Background
Clinical trials of ICPIs in early stage GA are ongoing. Nanostring (NS) GEP allows for simultaneous interrogation of a wide range of genes involved in immune signaling. We conducted a retrospective analysis of resected GAs to gain insight on the immune landscape in this setting.
Methods
We profiled 45 archival GAs treated with upfront surgery (pT2N0 to pT4N3 AJCC7) using a 770-gene immune profiling panel on the NS platform. Clinicopathologic data were abstracted and overall survival (OS) was analyzed using Kaplan-Meier methods.
Results
The majority of patients (44/45) had ≥ stage II disease. NS GEP demonstrated 4 distinct molecular signatures, A-D. Group D exhibited the greatest downregulation of pro-inflammatory genes relative to the other 3. Grouping was not correlated to tumor location, Lauren histology, or stage. When applying an analogous 18 gene T-cell inflamed signature from the KEYNOTE-059 trial, 10/45 GAs matched this signature, indicative of higher likelihood of response to single agent ICPI. OS did not differ between T-cell inflamed vs. non-T-cell inflamed (Table). Comparing signatures associated with greatest (B+C) vs. least (A+D) CD8+ T-cell gene expression as a surrogate for T-cell infiltration, OS favored groups B+C. We also observed a 4 gene (MS4A1, CD19, BLK, TNFRSF17) B-cell signature significantly favored high vs. low expressors for OS.Table: 686P
| NS GEP (n) | Median OS (mo) | Log-rank Test |
|---|---|---|
| T-cell inflammed (10) | Not reached (NR) | p = .52 |
| Non-T-cell inflamed (35) | 59.9 | |
| Group B+C (24) | NR | p = .07 |
| Group A+D (21) | 33.0 | |
| High B score (23) | NR | p = .02 |
| Low B score (22) | 33.0 |
Conclusions
This data supports ongoing trials of ICPIs in early stage GA. ICPIs alone are unlikely to be sufficient for the majority of patients, necessitating biomarkers to guide addition of ICPIs to current multimodality approaches. Subsets of GAs were quantifiable by NS GEP to exhibit pre-existing CD8+ T-cell infiltration or B-cell signaling and more favorable prognosis. This suggests ICPIs alone or chemotherapy de-escalation strategies should be explored. Tumor-immune cell immunohistochemistry and MSI data will be presented.
Clinical trial identification
Legal entity responsible for the study
City of Hope.
Funding
NIH.
Editorial Acknowledgement
Disclosure
J. Chao: Research funding: Merck, Novonco Therapeutics; Consulting, Advisory roles: Lilly, Five Prime Therapeutics, Boston Biomedical, Merck; Speakers\' bureau: Merck. S.J. Klempner: Research funding: Leap Therapeutics; Consulting, Advisory roles: Lilly, Boston Biomedical, Astellas Pharma; Speakers\' bureau: Foundation Medicine. R. Pillai: Consulting, Advisory roles: Qiagen. All other authors have declared no conflicts of interest.
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