Abstract
Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.
Highlights
Oesophageal cancer causes around 572,000 new cases globally and ranks 9th out of the 10 most common new cancer cases worldwide
In the KEYNOTE-062 trial, pembrolizumab monotherapy showed non-inferiority compared to chemotherapy in patients with PD-L1 positive (combined positivity score (CPS) ≥ 1) advanced adenocarcinoma of the gastrooesophageal junction or stomach (HR 0.91, 95% CI 0.69–1.18)
At present we witness an encouraging development in gastro-oesophageal cancers by targeting immune checkpoints
Summary
Oesophageal cancer causes around 572,000 new cases globally and ranks 9th out of the 10 most common new cancer cases worldwide. Approximately 90% of all oesophageal cancer cases account for oesophageal squamous cell carcinoma (ESCC) and 10% for oesophageal adenocarcinoma (EAC), respectively [3]. In contrast to the low incidence of oesophageal cancer, stomach cancer ranks sixth place among common cancer cases worldwide (incidence ~1,033,000 cases), resulting in approximately 780,000 deaths. In many European countries, medical treatment does not depend so much on the localisation of the tumour (oesophageal versus gastric) but more on the histology (adenocarcinoma versus squamous cell carcinoma). This approach is supported by molecular analyses, which show that EAC is different from ESCC, but similar to gastric cancer [4]. Phase II and phase III trials demonstrate a benefit in the overall survival of patients suffering from oesophagogastric cancers by immune checkpoint inhibition in different therapy lines (Table 1)
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