Advances in the treatment of gastric cancer

To review the recent literature regarding treatment of gastric cancer.

Addition of postoperative radiation therapy to perioperative chemotherapy offers no survival benefit. Fluoropyrimidines, in particular 5-fluorouracil (5-FU), are the backbone for gastric cancer chemotherapy. S-1, an oral prodrug of 5-FU, has become the mainstay for gastric cancer chemotherapy in Japan. In a Japanese adjuvant chemotherapy trial, addition of docetaxel to standard S-1 chemotherapy improved disease-free survival; this regimen will become their new standard for adjuvant therapy. Microsatellite instability (MSI) high status is emerging as a favorable prognostic marker in resected gastric cancer and may indicate a group of patients who do not gain additional benefit from treatment with adjuvant chemotherapy. In metastatic gastric cancer, the addition of ramucirumab, an antivascular endothelial growth factor receptor 2-targeted antibody, to first-line chemotherapy did not improve survival over chemotherapy alone. Trifluridine/tipiracil treatment in chemotherapy-refractory gastric cancer improved survival compared to placebo and will emerge as a late-line therapy option. Phase II and III trials indicate activity for the immune checkpoint inhibitors pembrolizumab and nivolumab in chemotherapy-refractory gastric cancer and have led to US regulatory approval for pembrolizumab in chemotherapy-refractory programmed death ligand 1-positive or MSI-high gastric cancer, and approval in Japan for nivolumab in chemotherapy-refractory gastric cancer. However, a phase III trial in advanced gastric cancer failed to show a survival benefit for pembrolizumab over conventional paclitaxel. The poly ADP ribose polymerase inhibitor, olaparib, added to second-line paclitaxel in advanced gastric cancer failed to improve overall survival compared with paclitaxel alone.

Perioperative or postoperative adjuvant chemotherapy without radiation therapy remains the standard of care in gastric cancer. Addition of docetaxel to adjuvant S-1 will likely emerge as a new care standard. Pembrolizumab and nivolumab improve survival and now are treatment options in chemotherapy-refractory gastric cancer, especially for programmed death ligand 1-positive or MSI-high cancers.