Published online Jul 7, 2018. doi: 10.3748/wjg.v24.i25.2686
Peer-review started: March 30, 2018
First decision: May 17, 2018
Revised: May 23, 2018
Accepted: June 16, 2018
Article in press: June 16, 2018
Published online: July 7, 2018
Blockade of the programmed death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction (GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability (MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatment-refractory solid tumors with MSI status and the third-line or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.
Core tip: Programmed death ligand 1 (PD-L1) and microsatellite instability have recently entered into clinical practice as recommended biomarker testing for the use of immune checkpoint inhibitors in gastroesophageal cancer. However, PD-L1 still does not carry the highest sensitivity and specificity with variability in testing reported. Incorporation of PD-L1 expression from the tumor microenvironment with counting of immune cells appears to be the most effective strategy to date. Future efforts focusing on composite biomarkers in ongoing research from combinatorial immuno-oncology strategies are necessary to drive the field forward.