Neoadjuvant anti PD-1 / PD-L1 immune checkpoint inhibitors in locall y advanced gastric cancer with microsatellite insta bility



Gastric cancer is an aggressive malignant neoplasm of the digestive system. These tumors are genetically heterogeneous, and they could be subdivided into four groups. One of such groups, microsatellite instable (MSI) gastric cancer, is of interest considering prognosis and response to therapy. Immune checkpoint inhibitors present a perspective strategy in treating these tumors, however, there is currently insufficient data on their use in microsatellite instable gastric cancer.

Aim of this study was to evaluate objective response to neoadjuvant checkpoint inhibitors treatment in patients with MSI gastric cancer.

Materials and methods. We conducted a single-center non-randomized trial based on prospective analysis of case series in the State Budgetary Healthcare Institution «Saint Petersburg clinical scientific and practical center for specialized types of medical care (oncological)». 98 patients with locally advanced gastric cancer and cardioesophageal junction cancer (Siewert II and III) from 04.04.2019 to 16.03.2021 underwent testing for MSI. Those who were positive were enrolled. These patients were treated with Nivolumab or Pembrolizumab (investigator choice) in a neoadjuvant setting, then underwent radical surgery.

Results. Eleven patients were enrolled. They received Nivolumab or Pembrolizumab (investigator choice) in a neoadjuvant setting. Objective response was registered in 9 (81,8%) patients, two patients had stabilization. Nine patients (81,8%) underwent radical surgery. Pathologic complete response (pCR) was registered in 3 (33,3%). Postoperative complications were tracked and registered in accordance with Clavien-Dindo classification: grade 1 – 2 patients, grade 2 – 2 patients, grade 3 – 1 patient.

Conclusion. Incidence of microsatellite instability in gastric cancer in Russian population is 9,7%. Neoadjuvant immune
checkpoint inhibitors seems to be effective in this group of patients, however, further investigation in randomized clinical
trials is required.