Epstein-Barr virus and mismatch repair deficiency status differ between oesophageal and gastric cancer: A large multi-centre study

4040 Background: Recently, anti-programmed death 1 (PD-1) or its ligand (PD-L1) antibodies have shown promising activities in metastatic gastric cancer (MGC). However, little is known about detailed clinicopathological features of PD-L1 expression in patients (pts) with MGC. Methods: Pts with histologically confirmed MGC were eligible for this prospective observational study. PD-L1 expression on tumor cell (TC) or inflammatory cell (IC) and mismatch repair (MMR) were analyzed by immunohistochemistry (IHC). Epstein–Barr virus (EBV) was detected by in situ hybridization. The expressions of tyrosine kinase receptors (RTKs) such as HER2, EGFR and MET and cancer genome alterations were also evaluated by IHC or next generation sequencing. Results: A total of 237 pts were enrolled from September 2015 to December 2016. Samples of 199 (84.0%) pts were obtained from biopsy. PD-L1 expression on TC and IC was positive in 27 (11.4%) and 167 pts (70.5%), respectively. One hundred and seventy-one pts (72.2%) had positive PD-L1 expression on either TC or IC. MMR deficient (D-MMR) and EBV was detected in 14 (6.9%, n = 203) and 14 pts (5.9%, n = 237), respectively. PD-L1 expression on TC was more frequently observed in pts with D-MMR (P < 0.001) and KRAS mutation (P < 0.001), while that on IC was more frequently observed in pts with EBV+ (P = 0.045), lymph node metastasis (P = 0.001), and lung metastasis (P = 0.045). In contrast, pts with peritoneal metastasis were associated with less frequent PD-L1 expression in IC (P = 0.003). A significant association was not observed between PD-L1 expression and RTKs expression or presence of other gene alterations. D-MMR was significantly associated with intestinal type (P = 0.026) and absence of liver metastasis (P = 0.022). PD-L1 expression on either TC or IC was not prognostic factor (hazard ratio; 0.92, P = 0.741). Seven pts with D-MMR and seven pts with EBV+ MGC were enrolled in clinical trials of anti-PD-1/PD-L1 antibodies. Conclusions: PD-L1 expression in MGC was associated with some clinicopathological features. Impact of these characteristics on efficacy of anti-PD-1/PD-L1 antibody warrants further evaluation.

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The Right Treatment of the Right Patient: Integrating Genetic Profiling Into Clinical Decision Making in Advanced Gastric Cancer in Asia

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_321247 ◽

2021 ◽

pp. 1-8

Author(s):

Yoshiaki Nakamura ◽

Kohei Shitara ◽

Jeeyun Lee

Keyword(s):

Gastric Cancer ◽

Clinical Trials ◽

Mismatch Repair ◽

Epstein Barr Virus ◽

Clinical Decision Making ◽

Palliative Chemotherapy ◽

Metastatic Gastric Cancer ◽

Barr Virus ◽

Epstein Barr ◽

The Right

Gastric cancer is a major global health burden, especially when patients are diagnosed with recurrent or metastatic gastric cancer. Despite recent advances in treatment options with palliative chemotherapy, the median overall survival of patients with gastric cancer remains within 1 or 2 years after the diagnosis of metastatic disease. Gastric cancer is significantly more prevalent in eastern Asia (e.g., Japan and Korea). Next-generation sequencing (NGS) is rapidly being adopted as part of clinical practice in Korea and Japan, especially in patients with gastric cancer. Approximately 10% to 15% of the patients with gastric cancer who undergo NGS of their tumor specimen are allocated to target-matched clinical trials in Japan and Korea. In Japan and Korea, a cell-free DNA NGS panel is also actively being investigated as an alternative NGS test for patients with gastric cancer, which may reflect the tumor heterogeneity of gastric cancer. In Japan and Korea, multiple biomarkers, such as HER2, mismatch repair, Epstein-Barr virus, PD-L1 (combined positive score), EGFR, FGFR2, and CLDN18.2, are routinely assessed through immunohistochemistry or in situ hybridization before initiation of the first-line treatment in all patients with gastric cancer. Most tertiary cancer centers in Korea routinely perform HER2, mismatch repair, Epstein-Barr virus, and PD-L1 NGS before palliative chemotherapy in patients with gastric cancer. Biomarker evaluation for all patients with metastatic gastric cancer enables clinicians to identify available biomarker-based clinical trials early during the course of treatment, which expands treatment opportunities while patients are medically fit for clinical trials, if available. Comprehensive genomic profiling using a tissue or circulating tumor DNA NGS panel is considered necessary during second-line or subsequent treatment. It is hoped that a comprehensive molecular profiling strategy will facilitate greater use of precision medicine through molecularly targeted therapies for patients with gastric cancer in the near future.

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