Immunotherapy-based therapy versus chemotherapy for the neoadjuvant treatment of locally advanced dMMR/MSI-H gastric cancer.

e16121 Background: Growing evidences have suggested that immunotherapy represents a promising treatment for the neoadjuvant treatment of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer. The study aimed to compare the efficacy of neoadjuvant chemotherapy and immune checkpoint inhibitor (ICI)-based therapy in locally advanced, dMMR/MSI-H gastric cancer. Methods: Patients with MSI-H/dMMR locally advanced gastric cancer who received neoadjuvant chemotherapy, or ICI-based therapy between December 2018 and June 2023 at West China Hospital, Sichuan University were included. Patient data were collected from the prospectively database program of gastric cancer at our Hospital. Demographic and clinicopathologic data of patients were collected, including age, sex, ECOG performance status, primary tumor site, tumor staging, Lauren’s classification, tumor response, tumor regression grade (TRG), R0 resection, disease-free survival (DFS) and overall survival (OS). Results: A total of 21 patients treated with ICIs-based regimens and 18 patients treated with chemotherapy were included. In the ICI-based therapy group, 10 patients (47.6%) received dual PD-1 and CTLA-4 blockade, 1 patient (4.8%) received PD-1 blockade, and 10 patients (47.6%) received PD-1 blockade combined with chemotherapy. The median age of chemotherapy group and ICI-based group were 63 years (range, 36-76 years) and 59 years (range, 34-74 years), respectively. The rates of T4b and limited metastases were significantly higher in the ICI-based therapy group compared to chemotherapy group (T4b: 11.1% vs. 23.8%; limited metastases: 0% vs. 19.0%). 17 patients (94.4%) in the chemotherapy group and 20 patients (95.2%) in the ICI-based therapy group underwent R0 radical gastrectomy. One patient in the chemotherapy group did not undergo surgery due to disease progression. One patient in the ICI-based therapy group refused radical gastrectomy. For patients undergoing surgery, TRG 0-1 rate was obviously lower in patients receiving chemotherapy compared to those treated with ICI-based regimen (0.0% vs. 78.9%). The pCR rates in the chemotherapy group and ICI-based group were 0.0% and 57.9%, respectively. The pCR rates in patients treated with dual PD-1/CTLA-4 blockade and PD-1 blockade with chemotherapy were 66.6% and 50.0% (P = 0.65). Median DFS and OS have not yet been achieved due to the short follow-up time. Conclusions: Improvements in TRG 0-1 rate and pCR rate suggested that ICI-based treatments are favorable in the neoadjuvant setting of locally advanced, dMMR/MSI-H gastric cancer compared to chemotherapy. However, within the overall favorable group, there was no differences between dual PD-1/CTLA-4 blockade and PD-1 blockade with chemotherapy in term of pCR rate. Whether high pCR rates can translate into long-term survival benefits requires longer follow-up time.