Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1-Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial

Abstract

Purpose: The nProfiler 1 Stomach Cancer Assay (nProfiler1) ; designed to predict responses to fluorouracil-based adjuvant chemotherapy ; measures the expression of four gastric cancer target genes (GZMB ; WARS ; SFRP4 ; and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.

Materials and methods: The nProfiler1 assay stratifies patients into three groups (low-risk ; intermediate-risk ; and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS) ; including 5-year survival rates ; were calculated for the enrolled patients.

Results: Of the 153 patients in the POST trial ; 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months ; no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.0425) but not in the DS group (p=0.5940). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.

Conclusion: The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.