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Immune Checkpoint Inhibitors in the Treatment of Gastroesophageal Cancer

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Abstract

Immune checkpoint blockade has revolutionised the treatment of multiple cancers including melanoma, non-small cell lung cancer, urothelial and renal cell cancers. For patients with chemorefractory gastroesophageal cancer, treatment with anti-PD-1 therapy results in modest benefits in overall survival; nivolumab and pembrolizumab have been licenced in Japan and the USA, respectively, for this indication. However, initial enthusiasm has been tempered by the results of several large negative trials; immune checkpoint blockade is not superior to chemotherapy in the second-line setting or beyond in unselected or low PD-L1-expressing patients. Microsatellite instability is uncommon in patients with metastatic gastric cancer; however, it is associated with response rates of more than 50% and long-term survival benefit. Combining anti-PD-1 with cytotoxic chemotherapy and targeted therapies also shows promise to extend the benefit of immune checkpoint blockade to a larger proportion of gastroesophageal cancer patients. In this review we discuss recently reported and ongoing clinical research in immunotherapy for gastroesophageal cancer, and consider molecular biology associated with sensitivity and resistance to immune checkpoint blockade in gastroesophageal cancer patients.

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Authors and Affiliations

  1. Department of Haematology and Medical Oncology, CHU de Québec, Université Laval, Quebec City, Canada

    Maxime Chénard-Poirier

  2. Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

    Elizabeth C. Smyth

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  1. Maxime Chénard-Poirier
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Correspondence to Elizabeth C. Smyth.

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No sources of funding were used to assist in the preparation of this review.

Conflict of interest

Maxime Chénard-Poirier has no conflicts of interest to declare. Elizabeth C. Smyth declares honoraria from BMS, Five Prime Therapeutics, Servier, Gritstone Oncology and Celgene.

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Chénard-Poirier , M., Smyth, E.C. Immune Checkpoint Inhibitors in the Treatment of Gastroesophageal Cancer. Drugs 79, 1–10 (2019). https://doi.org/10.1007/s40265-018-1032-1

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