1436P - Better overall survival of male versus female patients with advanced gastric adenocarcinoma

Background

To understand if there is sex disparity in survival outcomes among the patients with advanced gastric adenocarcinoma (GAC), gastroesophageal junction adenocarcinoma (GEJAC), and esophageal adenocarcinoma (EAC).

Methods

The study included patients from Kaiser Permanente Northern California with metastatic or relapsed EAC, GEJAC and GAC whose tumor underwent next-generation sequencing. We used Cox regression modeling to examine association of male and female patients with overall survival (OS) adjusting for demographics, performance status, Charlson comorbidity index, receipt of chemotherapy, and six most common genomic alterations including HER2 overexpression/amplification, p53, KRAS, CDKN2A, PIK3CA co-mutation and Myc amplification.

Results

Among 875 eligible patients, 275 were female and 600 were male. OS for male versus female patients did not appear substantially different for the entire cohort (HR = 0.87; [95% CI, 0.74-1.03]), for EAC (HR = 1.0; [95% CI, 0.57-1.74]) and GEJAC (HR = 1.14; (95% CI, 0.77-1.67]) subgroups. However, OS of male versus female patients with GAC appeared substantially better (HR = 0.75; [95% CI, 0.60-0.93]). In addition, this substantial OS difference was preserved regardless of HER2 status, CDKN2A and PIK3CA mutation or Myc amplification. Intriguingly, despite overall there was no OS difference between male versus female GAC patients regardless of p53 mutation status, however, among GAC patients with a p53 mutation, male had substantially better OS than female patients only if tumor carried non-gain-of-function (non-GOF, HR = 0.59; [95% CI, 0.41-0.85]) but not gain-of-function mutation (GOF, HR = 1.46; [95% CI, 0.74-2.87]).

Conclusions

We have found that male versus female GAC patients had substantially better overall survival. Most intriguingly, the survival difference among patients with mutp53 was only observed if tumor carried mutp53 non-GOF. Our results for the first time identified a sex disparity in survival outcomes that is associated with a common molecular lesion and can have important implications in understanding the biology of GAC and in clinical practice for prognostic stratification.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.