Metastatic gastric cancer (mGC) patients with microsatellite instability-high (MSI-H) or Epstein-Barr virus (EBV)-positive tumours, or those with a positive (≥1%) combined positive score (CPS) respond best to pembrolizumab PD-1 immunotherapy.

“Trials with pembrolizumab or nivolumab have demonstrated a rather wide range of response rate (10–26%) in mGC in the salvage setting with no selective biomarker or PD-L1 positivity. Hence, in order to enhance the efficacy of anti-PD-1 therapy in mGC, there is an urgent need to identify precise predictive biomarkers to better select gastric cancer patients who might benefit most from immunotherapy.”

The Korean researchers led by Jeeyun Lee and Won Ki Kang of the Samsung Medical Center in Seoul, reported on the molecular characterisation of tissues and circulating tumour DNA (ctDNA) in 61 mGC patients who received salvage anti-PD1 treatment with pembrolizumab in a prospective Phase II clinical trial.

Results

Dramatic overall response rates (ORR) to pembrolizumab were observed in EBV-positive and MSI-H mGC; 87.5% and 100%, respectively. Interestingly, EBV-positivity and MSI-H were found to be mutually exclusive in this study.

The CPS was available in 90% (55/61) of patients and those with a CPS-positive (≥1%) tumour had a significantly higher ORR when compared to patients with CPS-negative (<1%) gastric cancers; 50.0% vs 0.0% (p<0.001).

Furthermore, the investigators looked at changes in ctDNA levels. A decreased level of ctDNA 6-weeks post-treatment was associated with an improved response rate and progression-free survival.

The FDA has approved pembrolizumab for relapsed or refractory advanced gastric cancer with a CPS≥1.

Reference

Kim ST, et al. Nature Med. 2018;DOI: 10.1038/s41591-018-0101-z.

Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).

© Copyright 2018 MediPaper Medical Communications Ltd. – EBV pembrolizumab gastric cancer – MSI-H pembrolizumab gastric cancer – CPS pembrolizumab gastric cancer – MSI, EBV, CPS predict pembrolizumab outcome in gastric cancer.