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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
PD-L1-high gastric cancer expresses the immune checkpoint protein PD-L1 on tumour and immune cells, and this is the group in which nivolumab or pembrolizumab added to chemotherapy clearly extends life. The benefit shrinks as the score falls, so regulators now restrict the antibodies to tumours with at least some PD-L1 expression.
PD-L1 in stomach cancer is scored with the combined positive score, the number of PD-L1-staining tumour cells, lymphocytes and macrophages divided by the number of viable tumour cells, using the 28-8 or 22C3 antibody. Epstein-Barr virus-positive tumours, about one in eleven, express PD-L1 heavily and respond best of all; microsatellite-unstable tumours do too. Scores of 5 or above with the 28-8 assay and 1 or above with 22C3 have become the practical thresholds, and the two assays are not perfectly interchangeable.
CheckMate 649 (Lancet 2021) randomised HER2-negative advanced gastric, junctional and oesophageal adenocarcinoma to nivolumab plus oxaliplatin-fluoropyrimidine chemotherapy or chemotherapy alone; in the combined positive score 5 or above group median overall survival rose from 11.1 to 14.4 months, and in all randomised patients from 11.6 to 13.8 months, with the gain concentrated in tumours with higher scores and persisting at five years. KEYNOTE-859 (Lancet Oncology 2023) did the same with pembrolizumab, improving median survival from 11.5 to 12.9 months overall, from 11.4 to 13.0 months in score 1 or above and from 11.8 to 15.7 months in score 10 or above. Chinese trials with tislelizumab and sintilimab followed the same pattern.
| Setting | Approach | Guideline |
|---|---|---|
| Advanced, first line, CPS 5 or above | Nivolumab with FOLFOX or CAPOX (CheckMate 649) or pembrolizumab with platinum-fluoropyrimidine chemotherapy (KEYNOTE-859). | not mapped |
| Advanced, first line, CPS 1 to 4 | PD-1 antibody with chemotherapy is permitted in the United States and offered with a smaller expected gain; chemotherapy alone or zolbetuximab where claudin 18.2 is positive. | not mapped |
| Resectable stage II to III | Perioperative FLOT with durvalumab (MATTERHORN), given irrespective of PD-L1 score. | not mapped |
| Second line | Ramucirumab with paclitaxel (RAINBOW); no established role for continued PD-1 blockade. | not mapped |