Results of using Pembrolizumab and Nivolumab, immune checkpoint inhibitors (ICIs), in third-line therapy for patients with metastatic gastric cancer. Experience of Moscow oncology service

Background . There is limited data on the effectiveness of immune checkpoint inhibitors (ICIs) in third-line therapy for metastatic gastric cancer. The aim of the study was to compare progression-free survival (PFS) and overall survival (OS) in patients with metastatic gastric cancer receiving third-line immunotherapy or chemotherapy. Material and Methods . In third-line treatment for metastatic gastric cancer, the long-term outcomes (PFS and OS) of ICI (n=93) or chemotherapy (n=77) were retrospectively evaluated. The study group comprised 170 patients; 63.4 % were males and 53.2 % were females. The median age was 65.5 and 63.7 years in ICN and chemotherapy groups, respectively. ECOG 2 was 22.6 % and 16.9 %, respectively. The ICI group had worse PFS in second-line therapy (2.8 and 4.8 months, p=0.0014), and fewer patients continued treatment after progression (14 % and 39 %, p=0.002). In the chemotherapy group, 80 % of patients received ICIs in fourthand later lines of treatment. Results . The analysis showed that PFS was better in the chemotherapy group than in the ICI group (4.3 vs 2.4 months, p=0.12, HR 1.28, 95 % CI 0.94–1.76), OS was also better in the chemotherapy group than in the ICI group (7.8 vs 4.8 months, p=0.064, HR 1.35, 95 %CI 0.98–1.85). The influence of the CPS level (0–9/unknown and ≥10) in the ICI group was not found: PFS 2.1 and 2.4 months (p=0.75), OS 4.1 and 4.4 months (p=0.62). When comparing PFS and OS in patients with MSI/dMMR who received ICI (n=6) and chemotherapy (n=5), no benefits of using ICT was shown (PFS 3.4 and 9.7 months, p=0.75, and OS 11.9 and 13.0 months, p=0.56). During the first follow-up, disease stabilization was observed in 26 % and 44.2 % of patients, respectively (p=0.015 %). Conclusion. The use of ICT in third-line treatment for metastatic gastric cancer was inferior to standard treatment regimens in terms of PFS and OS (regardless of CPS level and presence of MSI). Given the risks of rapid progression in ICI-treated patients, the presence of a small subgroup of patients (no more than 10 %) who benefit from classical treatment approaches with long follow-up periods, it is necessary to continue the search for factors associated with the effectiveness of ICI.