Gastric inflammatory prognostic index (GIPI) to predict efficacy of PD-1/PD-L1 immune checkpoint inhibitors in metastatic gastroesophageal junction (GOJ)/gastric cancer (GC) patients.

Abstract

4530 Background: ICIs demonstrated improved overall survival (OS) in heavily pre-treated mGOJ/GC pts. Pts selection exclusively based on PD-L1 tissue expression appears to be suboptimal, despite data from subgroup analyses of KEYNOTE trials. Strong rationale suggests a potential predictive role of inflammatory biomarkers in ICIs treated mGOJ/GC pts. Methods: Ten systemic inflammatory markers [platelets, monocytes, neutrophil/lymphocyte ratio (NLR), platelets-lymphocyte ratio, lymphocytes, sum of mononuclear cells, albumin, lactate dehydrogenase, c-reactive protein (CRP) and serum globulin] were retrospectively analyzed at baseline in 57 mGOJ/GC pts with unknown PD-L1 status treated in second-line with ICIs, and correlated with OS. Least Absolute Shrinkage and Selection Operator (LASSO) method was used to select variables (preliminarily subject to optimal coding using HR smoothed curves for OS) with the highest prognostic value. Selected variables were then analyzed in a multivariate Cox Regression Model and used to build a GIPI nomogram. Results: NLR and CRP taken as continuous variables and albumin categorized as < vs > 30 g/dL were found as the most meaningful independent predictors of OS and used to build the GIPI nomogram. Nomogram-based lowest (l), mid-low, mid-high and highest (h) risk quartiles were associated with median(m)OS of 14.9, 7.1, 5.6 and 2.1 months (mos), respectively [HR of l vs h 4.94, p 0.0002]. By optimally dichotomizing CRP and NLR, pts with one or more of the following risk factors: NLR >6, CRP >15 mg/L, albumin <30 g/dL (n: 29) had a mOS of 3.9 mos vs 14.2 mos of pts with no risk factor (n: 28) (HR 2.48, p 0.001). Conclusions: GIPI, combining NLR, CRP and Albumin, is the first inflammatory index with a significant prognostic value in mOGJ/GC pts receiving second-line ICIs. Its implementation in correlation with PD-L1 expression in the present cohort is ongoing. GIPI merits validation in independent cohorts and prospective clinical trials.