Abstract

BACKGROUNDIntracranial metastatic disease (IMD) is a mortality-driving complication of gastrointestinal (GI) cancers. In breast cancer, ERBB2 positivity is associated with shorter overall survival (OS) and increased risk of IMD, and while ERBB2 status is relevant in primary GI cancer, no study has directly assessed the relationship of ERBB2 status and IMD in these patients. METHODSRecords for adult patients with GI cancer and IMD, treated with ERBB2-therapy between 2005 and 2018 were retrieved from ICES. Baseline characteristics were compared between subcohorts stratified by IMD and ERBB2 statuses. Kaplan-Meier and Cox regression analyses were performed to estimate survival. RESULTSRecords for 99,256 patients with GI cancer were collected, and IMD was diagnosed in 2002 patients. The highest IMD incidence rate was among patients with esophageal cancer (5.5%). Among patients with ERBB2+ disease, 306 had gastric (9 IMD), 168 esophageal (15 IMD), and 17 colorectal cancer. Diagnosis of IMD was associated with shorter OS among patients with colorectal (HR 3.0; 95% CI 2.9–3.2), gastric (HR 1.7; 95% CI, 1.5–1.9), and esophageal cancers (HR 1.2; 95% CI, 1.1–1.4). Post-IMD ERBB2-targeted therapy was not associated with OS among patients with ERBB2+ esophageal (HR 0.5; 95% CI, 0.2–1.2; n = 15) or gastric cancer (HR 0; 95% CI 0–Inf; n = 9). CONCLUSIONOur study assessed patients with ERBB2+ GI cancer and IMD. Diagnosis of IMD was associated with shorter survival in gastric, esophageal, and colorectal cancers. Post-IMD ERBB2 therapy was not associated with OS, and IMD diagnosis was associated with prolonged survival in patients with stage 4 ERBB2+ disease, although interpretation of these results is complicated by small sample size and selection bias. Our results motivate increased reporting and inclusion of patients with ERBB2+ GI cancers in clinical trials.

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