Abstract 1425P
Background
Epstein-Barr virus associated gastric cancer (EBVaGC) is a distinct subtype of GC, whose response to immunotherapy were variable among cohorts. The ability and mechanisms of EBVaGC to benefit from immune checkpoint blockage (ICB) need to be clarified.
Methods
Twelve advanced EBVaGC received ICB, including eight patients treated with anti-PD-1/L1 monotherapy and four treated in combination with anti-CTLA-4. Their response and survival outcome were evaluated and compared with 29 EBV-/Mismatch Repair deficient (dMMR) and 47 EBV-/MMR proficient (pMMR) GC patients treated with anti-PD-1/L1. Univariate and multivariate analyses were performed to evaluate the predictive value of EBV status in GC under ICB treatment. Tumor infiltrating immune cells were examined by mIHC, and gene mutation and copy number variation were analyzed by next generation sequencing, with tumor samples obtained prior ICB treatment.
Results
Twelve EBVaGC yielded an objective response rate of 41.7%. EBV+/pMMR patients had more favorable PFS and OS to EBV-/pMMR cohort (P<0.001; P= 0.015) and comparable result to EBV-/dMMR group (P = 0.79; P = 0.83). EBV status was independently associated with PFS (P =0.046) and OS (P =0.028). In EBVaGC treated with anti-PD-1/L1 monotherapy, the density of CTLA-4 in both tumor (P =0.033) and stromal (P=0.008) were significantly higher in the non-response group. Interestingly, EBVaGC patients received dual ICB tended to have better prognosis than the patients under mono-immunotherapy (P =0.222). All the EBVaGC patients with SMARCA4 mutation attained PR (P=0.045) and had numeral longer PFS and OS than their wild-type counterpart (P =0.399; P =0.484). 13q12.12 deletion was enriched in non-response group (p=0.080) and a positive correlation was observed between the copy number of 13q12.12 and tumor regression (R2=0.58). Furthermore, patients with 13q12.12 deletion had unfavorable PFS and OS (P =0.070; P =0.332).
Conclusions
EBV status was a favorable biomarker for GC immunotherapy. EBVaGC may benefit more from anti-PD-1/L1 combined with anti-CTLA-4. SMARCA4 and 13q12.12 deletion were potential biomarkers of EBVaGC patients regarding to ICB.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.