The results of the use of immune checkpoint inhibitors (ICI) pembrolizumab and nivolumab in the first line treatment of patients with metastatic gastric cancer. The experience of the oncological service of Moscow

Introduction: the use of immunotherapy agents in combination with chemotherapy has shown its effectiveness in randomized trials for the first-line treatment of metastatic gastric cancer. The paper considers the experience of the Moscow oncological service in evaluating the effectiveness of pembrolizumab and nivolumab in patients with metastatic gastric cancer, depending on morphological (CPS, MSI) characteristics.Aim of the study: to compare progression-free survival (PFS) and overall survival (OS) in patients with advanced gastric cancer who underwent immunotherapy (as monotherapy or in combination with chemotherapy) or standard chemotherapy with oxaliplatin and fluoropyrimidines.Patients and methods: 194 patients met the inclusion criteria. Of these, 52 patients received checkpoint inhibitors (ICI) (18-immunotherapy alone; 31-in combination with chemotherapy, 15 patients received pembrolizumab and 37 patients received nivolumab); 142 patients received chemotherapy CAPOX or FOLFOX without ICI. The median follow-up was 29.5 months (17.4-62 months). Males were 55.8 % and 57.7 % with average age of 64.5 and 65.9 years, ECOG 2 was detected in 15.4 % and 8.5 % of patients. Other characteristics were also comparable: CPS > 10 69.2 % and 19.7 % (p = 0.0001), MSI 26.2 % and 4.9 % (p = 0.009), 2nd lines and further treatment were received by 36.5 % and 69.3 % (p = 0.0001), respectively.Results: in the entire population PFS was 7.9 months and 6.4 months (HR 0.46; 95 % CI 0.32-0.67, p = 0.0001), and OS was 17.3 months and 14.6 months (HR 0.71; 95 % CI 0.49-1.04, p = 0.076), respectively. The univariate analysis showed that only 1 prognostic factor for survival - the number of organs with metastases. In accordance with this, in case of the presence of metastases in 1-2 organs the use of ICI had an advantage in terms of PFS (p = 0.051 and p = 0.001), while in case of 3 or more organs involved there was no advantage (p = 0.62). Assessing the effect of the CPS level in patients with MSS phenotype, it was shown that at CPS0-9 there was no advantage in PFS (6.1 months and 6.9 months, p = 0.7) and OS (8.8 months and 14.9 months, p = 0.39). With CPS > 10, an advantage was noted when adding ICI for PFS (9.9 months and 4.4 months, p = 0.0001), and OS 18.2 months and 12.1 months (p = 0.23). However, the results did not differ at the CPS level > 50. When evaluating patients with MSI, we demonstrated that with a median PFS of 6.6 months and 5.2 months, respectively (HR 0.48; 95 % CI 0.17-1.4; p = 0.165), the median OS in patients who received ICI with or without CT was significantly higher - 24.3 months and 11.1 months, respectively (HR 0.4; 95 % CI 0.13-1.21; p = 0.11).Conclusions: the use of ICI in the first line therapy for metastatic gastric cancer (compared with CT alone) increases the proportion of patients living without progression for 12 months or more, and the overall survival rate was also increased by more than 2 times. The threshold level of CPS for ICI assignment needs to be > 10. The relationship between the effectiveness of immunotherapy and PD-L1 expression in gastric cancer with MSI tumors requires further study in a larger sample of patients. Information at the CPS level, the presence of MSI and HER2 / neu should be presented at the time of discussion of treatment tactics at the onset of metastatic disease.