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September 3, 2020

Pembrolizumab in First-line Gastric Cancer: Win, Lose, or Draw?

Author Affiliations
  • 1Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, United Kingdom
  • 2Department of Internal Medicine, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
JAMA Oncol. Published online September 3, 2020. doi:10.1001/jamaoncol.2020.2436

Gastric cancer (GC) is common and, when advanced, usually fatal; median overall survival (OS) for patients with advanced GC who are enrolled in contemporary first-line trials is approximately 1 year. Checkpoint inhibition (CPI) is a well-established therapy for many highly and moderately immunogenic tumors. In contrast, and until recently, the benefit of CPI in unselected metastatic GC has only been proven in randomized clinical trials when treatment with nivolumab was compared with placebo in patients with chemorefractory GC.1 In the second-line GC KEYNOTE-061 trial, treatment with pembrolizumab failed to show a significant survival benefit when compared with minimally active paclitaxel chemotherapy.2 Similarly, results for maintenance CPI blockade with avelumab following induction chemotherapy have been negative.3 In each of these negative trials, patients with higher levels of programmed cell death ligand 1 (PD-L1) expression showed a trend toward better survival. However, preliminary data from treatment-naive patients with GC in the KEYNOTE-059 trial suggested high rates of objective response for patients with PD-L1–positive tumors (combined positive score [CPS] of 1 or greater) treated with pembrolizumab plus chemotherapy.4

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