Clinical and Molecular Predictors of Response to Immune Checkpoint Inhibitors in Patients with Advanced Esophagogastric Cancer

Abstract

Immune checkpoint inhibitors (ICIs) are effective in only a minority of patients with esophagogastric cancer (EGC). Here, we aimed to identify predictors of durable clinical benefit to ICI in EGC. Experimental Design: Patients with advanced EGC treated with ICIs at Memorial Sloan Kettering Cancer Center were identified. Clinicopathologic variables were assessed. In patients profiled by MSK-IMPACT targeted sequencing, outcomes were correlated with tumor genomic features. Results: One-hundred sixty-one patients were treated with ICIs (110 with anti-PD-1/PD-L1 antibodies and 51 with anti-CTLA-4 and PD-1/PD-L1 antibodies). The median progression-free survival (PFS) and overall survival (OS) were 1.7 and 4.9 months, respectively. Greater number of disease sites (≥3), liver metastases, treatment with ≥3 prior therapies and ECOG performance status ≥2 were associated with poorer PFS and OS. Patients treated with combination ICI and those with PD-L1 positive tumors had improved outcomes. There was no difference in outcomes between patients treated with antibiotics during or in the 2 months preceding ICI treatment versus those who were not. Occurrence of irAEs was associated with improved OS. In genomically profiled tumors (n=89), survival was associated with increasing tumor mutation burden (TMB). However, in multivariable analyses and when microsatellite unstable (MSI) patients were excluded, a significant association was no longer observed.

Identification of an Immune-Related Prognostic Signature Associated with Immune Infiltration in Melanoma

“…In our model, the risk score was in contrast to the TMB pattern to determine the prognosis of melanoma patients, suggesting that the poor prognosis of the high-risk group may be due to fewer mutant genes in this group. Recently, some studies have indicated that increased tumor mutation loads were associated with survival benefit from both anti-CTLA-4 and anti-PD-1 therapy in multiple malignancies such as melanoma [27], lung cancer [28], and esophagogastric cancer [29]. Consistent with these studies, our results showed that melanoma patients in the low-risk group with higher immune infiltration and tumor mutation load might respond well to immunotherapy, though larger studies will be necessary to confirm this finding.…”

Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

“…Interestingly, a large proportion of patients with esophageal cancer harbor tumors with high a TMB 68 . Greally et al examined the relationship between TMB and survival in 89 patients with esophagogastric cancer treated with immunotherapy and found that TMB was associated with a significant improvement in OS in univariate analyses 69 . However, the observed association did not persist after adjusting for other risk factors and after the exclusion of MSI tumors.…”

Achievement of complete response to nivolumab in a patient with advanced sarcomatoid hepatocellular carcinoma: A case report

“…Use of ICIs is a rapidly developing immunotherapy method in recent years[ 10 ]. ICIs can kill tumors by primarily restoring the suppressed immune function of the body.…”