Advances in the treatment of gastric cancer.

PURPOSE OF REVIEW: To review the recent literature regarding treatment of gastric cancer.

RECENT FINDINGS: 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.

SUMMARY: 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.