Effect of peripheral ANGPTL3 on the efficacy of anti-PD1 therapy for advanced gastric cancer.

Abstract

425 Background: Anti-PD1/PDL1 therapy has attracted great attention in cancer therapy in recent years, whereas only a small portion of patients can benefit from it. We attempted to identify a molecule that is associated with anti-PD1/PDL1 therapeutic efficacy by proteomic profiling of plasma of patients with advanced gastric cancer (AGC) receiving nivolumab monotherapy in the WJOG10417GTR study. Methods: We collected peripheral blood from 91 AGC patients before and after nivolumab monotherapy according to the protocol (No. 2017-473) approved by the IRB. Multiple proteins in plasma were measured using the 7k SomaScan v4.1, and the concentrations of potential candidate molecules in plasma were verified by ELISA. The relationship between these levels and patient prognosis was statistically analyzed. This study was supported by Ono Pharmaceutical and Bristol Myers Squibb. Results: Proteomic data revealed that 14 molecules both before and after treatment were significantly higher in patients showing progressive diseases (PD) as the best response than those in patients not showing PD. Among them, ANGPTL3 levels at post-treatment were >10-fold higher in PD patients than in non-PD patients. When comparing progression-free survival (PFS) and overall survival (OS) between two groups divided by the cutoff value, patients with high levels of ANGPTL3 both before and after treatment had significantly worse prognosis (Table). Conclusions: ANGPTL3 may be a promising biomarker to predict responses to anti-PD1/PDL1 therapy, and ANGPTL3-targeting strategies may contribute to improving clinical outcomes in anti-PD1/PDL1 therapy for GC. Clinical trial information: UMIN000032686 . PFS (high vs low) OS (high vs low) Methods Sample collectiontimings Median (months) HR P values Median (months) HR P values Proteomic analysis Pre 1.4 vs 2.0 2.6 0.001 4.5 vs 9.0 2.4 0.006 Post 1.3 vs 2.6 2.4 0.002 4.5 vs 9.9 2.3 0.002 ELISA Pre 1.0 vs 2.0 2.8 0.001 2.8 vs 8.1 2.6 0.003 Post 1.5 vs 2.0 1.5 0.234 4.9 vs 9.0 2.2 0.024