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Pembrolizumab for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction cancer: an evidence-based review of place in therapy

Authors Mehta R, Shah A, Almhanna K

Received 30 May 2018

Accepted for publication 14 September 2018

Published 4 October 2018 Volume 2018:11 Pages 6525—6537

DOI https://doi.org/10.2147/OTT.S152513

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr William Cho


Rutika Mehta,1 Anand Shah,2 Khaldoun Almhanna3

1Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA; 2Department of Pharmacy, Moffitt Cancer Center, Tampa, FL 33612, USA; 3Department of Hematology/Oncology, Lifespan Cancer Institute, Providence, RI, USA

Abstract: Gastric and esopahgeal cancers account for the six most common causes of cancer death worldwide. Locally advanced resectable cancers have a 5-year life expectancy of 30%. Despite use of chemotherapy, median overall survival for stage IV cancer rarely exceeds 1 year. A subset of gastric cancers such as microsatellite-instable tumor and Epstein–Barr virus-positive tumors have a rich immune infiltrate that makes them more responsive to immune-directed therapies. Tumors can evade T-cell-mediated “immune surveillance” by activating the programmed cell death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway. Targeting PD-1 and thus de-engaging them from its ligands can help restore immunogenicity. Pembrolizumab is the first immunotherapy to be approved by US FDA for PD-L1 expressing gastric and gastroesopahgeal junction (GEJ) cancers after they have progressed on at least two prior lines of treatment. While PD-L1 positivity does not define tumor’s responsiveness to pembrolizumab, PD-L1-positive tumors have better overall response rates. The treatment is usually well tolerated and has a favorable adverse events profile. The exact setting for use of pembrolizumab remains to be determined. Pembrolizumab failed to improve overall survival when administered as second-line treatment for advanced, metastatic gastric and GEJ cancers. There are several ongoing studies with various combinations and different settings not only with pembrolizumab but also with other checkpoint inhibitors.

Keywords: gastric cancer, gastroesophageal junction cancer, pembrolizumab, PD-1

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