Efficacy of immunochemotherapy (ICT) in patients (pts) with metastatic gastric cancer (mGC) in context of ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) and PD-L1 expression: Results of the meta-analysis.

Abstract

e16062 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 1 st 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 (evaluation form 2a), 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 6010 pts (CT – 3000 and ICT – 3010). 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; I 2 = 0%, p for heterogeneity 0.74) in groups with ICT in ITT population. Results according to PD-L1 expression presented in table. Conclusions: Addition of anti-PD1 and CT with oxaliplatin and fluoropyrimidines in 1 st line in pts with mGC meets the definition of clinical benefit according to the ESMO-MCBS only by selecting pts with PD-L1 expression CPS ≥10. PDL CPS n of trials HR (95% CI) p I 2 (p for heterogeneity) ESMO-MCBS <1 4 0.93 (0.8-1.09) 0.38 0% (0.95) 2 <5 3 0.92 (0.82-1.04) 0.18 0% (0.88) 2 <10 4 0.88 (0.82-0.96) 0.003 0% (0.91) 2 ≥1 4 0.75 (0.7-0.8) <0.001 0% (0.92) 3 ≥5 4 0.7 (0.64-0.77) <0.001 0% (0.79) 3 ≥10 5 0.65 (0.59-0.71) <0.001 0% (0.91) 4