The Impact of Molecular Subtype on Efficacy of Chemotherapy and Checkpoint Inhibition in Advanced Gastric Cancer

Abstract

Purpose: We evaluated the association between molecular subtypes of advanced gastric cancer (AGC) and the efficacy of standard chemotherapy or immune checkpoint inhibitors.Experimental Design: Patients with AGC who received systemic chemotherapy from October 2015 to July 2018 with available molecular features were analyzed. We investigated the efficacy of standard first-(fluoropyrimidine + platinum ± trastuzumab) and second-line (taxanes ± ramucirumab) chemotherapy, and subsequent anti-PD-1 therapy in patients with four molecular subtypes: MMR-D, EBV+, HER2+, and allnegative.Results: 410 patients were analyzed: MMR-D 5.9%, EBV+ 4.1%, HER2+ 13.7%, and all-negative 76.3%. In 285 patients who received standard first-line chemotherapy, the median progression-free survival (PFS) times were 4.2, 6.0, 7.5, and 7.6 months and the objective response rates (ORRs) were 31%, 62%, 60%, and 49% in MMR-D, EBV+, HER2+, and all-negative subtypes, respectively. Multivariate analysis showed shorter PFS in MMR-D vs. all-negative patients (HR 1.97, 95% confidence intervals: 1.09-3.53, P = 0.022). In second line setting, there were no significant differences in efficacy.In 110 patients who received anti-PD-1 therapy, median PFS times were 13.0, 3.7, 1.6, and 1.9 months and the ORRs were 58%, 33%, 7%, and 13%, respectively. Twelve MMR-D patients received subsequent anti-PD-1 therapy and showed longer PFS compared with that in ten (83%) patients who received earlier-line chemotherapy.Conclusions: MMR-D might result in shorter PFS with first-line chemotherapy for AGC. Subsequent anti-PD-1 therapy achieved higher ORR and longer PFS than prior chemotherapy in most MMR-D patients, supporting the earlier use of immune Research.

A Durable Response after the Discontinuation of Nivolumab in an Advanced Gastric Cancer Patient

“…3). This result was consistent with that reported in previous reports (20,21). However, there are no reports on the predictive markers for a durable clinical benefit after the discontinuation of ICIs in AGC, and further study in many similar cases will be needed to clarify this, regardless of the distinctive features seen in our patient.…”

Racial and ethnic disparities in mortality from gastric and esophageal adenocarcinoma

“…Finally, it is possible that there are underlying biological and pathophysiological factors that predispose certain racial and ethnic groups to have more aggressive disease and worse mortality rates, such as minorities in NCGC and non‐Hispanic whites in CGC and EAC. Early findings suggest that differences in molecular subtypes of advanced gastric cancer impact efficacy of various treatment modalities 37 . Research is needed into whether these molecular profiles might differ between racial/ethnic groups and may account for some of these disparities.…”

Construction and Analysis of the Tumor-Specific mRNA–miRNA–lncRNA Network in Gastric Cancer

“…Gastric cancer is a major cause of cancer-related mortality worldwide ( Van Cutsem et al, 2016 ). It is a serious form of cancer characterized by limited chemotherapy regimens and complex patterns of tumorigenesis and progression in different subtypes ( Erdem et al, 2018 ; Kubota et al, 2020 ). There have been exceptional advancements in the interpretation of the molecular pattern of gastric cancer through research projects including the Cancer Genome Atlas (TCGA) ( Cancer Genome Atlas Research N, 2014 ) and the Asian Cancer Research Group (ACRG) ( Cristescu et al, 2015 ) in recent years; however, current classifications are not sufficient to describe the vast differences in prognoses and summarize overall genomic characteristics, even for patients who are recognized as belonging to the same molecular subtypes.…”