Efficacy of chemoimmunotherapy in first-line treatment of patients with disseminated gastric cancer depending on PD-L1 expression and clinical benefit according to the ESMO-MCBS and RUSSCO criteria: results of a meta-analysis

Background: Addition of anti-PD1 antibodies to chemotherapy (CT) in pts with mGC has become a standard of care. However, there is no consensus on the threshold value of PD-L1 expression in the tumor as a predictor of the effectiveness of this approach (from the opinion that it is possible not to select on expression, to the selection of pts with a CPS ≥ 10). Therefore, we performed systemic review and meta-analysis to evaluate the efficacy of ICT depending on the expression of PD-L1 and compliance with the indicators of clinical benefit in accordance with ESMO-MCBS.

Methods: We conducted a search of all prospective randomized phase III studies in PubMed, ASCO and ESMO congresses for all years before June 2023, with anti-PD1 antibodies and CT with oxaliplatin and fluoropyrimidines in 1st line in pts with Her-2 negative mGC. Primary outcome was hazard ratio (HR) for OS and 95 % confidence interval (CI). Fixed or random effects were used for analysis, depending on heterogeneity. Meta-analysis was conducted by Review Manager Ver. 5.3. When calculating the number of points according to ESMO-MCBS, the median OS in the control group was more than 12 months and a point was added for improving the quality of life.

Results: We identified 6 trials (ATTRACTION-4, CHECKMATE-649, KEYNOTE-859, ORIENT-16, RATIONALE-305 and GEMSTONE-303), which included 5531 pts (CT — 2762 and ICT — 2769). According to the results of the meta-analysis there was a significant improvement in OS (HR 0.8, 95 % CI 0.75–0.86; p < 0.001; I2 = 0 %, p for heterogeneity 0.74) in groups with ICT in ITT population. Statistically significant improvement in overall survival was observed with PD-L1 CPS expression ≥ 5 (OR 0.71, 95 % CI 0.65–0.78; p < 0.001; I2 = 0 %) with ESMO-MCBS grading level of 3 points and RUSSCO — IC and among patients with PD-L1 CPS expression ≥ 10 (OR 0.65, 95 % CI 0.59–0.71; p < 0.001; I2 = 0 %) and ESMO-MCBS grading level of 4 points and RUSSCO — IB.

Conclusions: Addition of anti-PD1 and CT with oxaliplatin and fluoropyrimidines in 1st line in pts with mGC meets the definition of clinical benefit according to the ESMO-MCBS and RUSSCO only by selecting pts with PD-L1 expression CPS ≥ 10.

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