TOPLINE

A recent analysis suggested that, while ERBB2-low advanced gastric cancer was associated with significantly shorter progression-free survival (PFS) and overall survival than ERBB2-null disease in unadjusted analyses, ERBB2 status was not independently associated with survival outcomes after adjustment for baseline clinical characteristics.

METHODOLOGY

• The prognostic impact of ERBB2-low disease among patients with advanced gastric cancer remains unclear.
• To evaluate whether ERBB2 status is independently associated with survival outcomes, researchers conducted an international, multicenter retrospective cohort study, which included 522 patients aged 18 years and older with advanced metastatic gastric cancer.
• Patients were classified as ERBB2-null (immunohistochemistry [IHC] score of 0) or ERBB2-low (IHC 1+ or IHC 2+ and in situ hybridization negative).
• Overall, 488 patients (93.5%) received first-line systemic therapy for metastatic disease, most commonly doublet chemotherapy with or without immunotherapy; fluoropyrimidine-based chemotherapy was used in 92% of patients.
• The primary outcomes were PFS and overall survival.

TAKEAWAY

• ERBB2-low status was associated with significantly shorter median PFS (7.2 months vs 8.7 months; hazard ratio [HR], 1.36; P = .003) in univariable analysis.
• ERBB2-low status was also associated with significantly shorter median overall survival (15.8 months vs 23.1 months; HR, 1.34; P = .006).
• However, in multivariable analysis, ERBB2 status was not independently associated with PFS (HR, 1.16; 95% CI, 0.93-1.46) or overall survival (HR, 1.13; 95% CI, 0.89-1.44).
• Several baseline clinical factors, rather than ERBB2 status, were independently associated with survival outcomes. Male sex, ECOG performance status of 2 or higher, diffuse histology, de novo metastatic disease, elevated carcinoembryonic antigen levels, and ascites were independently associated with worse overall survival, whereas primary tumor resection was associated with improved overall survival.

IN PRACTICE

“These findings suggest that ERBB2-low status alone may be insufficient for prognostic stratification,” the authors wrote.

SOURCE

The study, led by Beliz Bahar Karaoğlan, MD, Department of Medical Oncology, Ankara University Faculty of Medicine, Ankara, Turkey, and Eduardo Terán, MD, PhD, Gastrointestinal Cancer Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain, was published online in JAMA Network Open.

LIMITATIONS

The study was retrospective, which may introduce inherent biases. ERBB2 assessment was primarily based on single-site endoscopic biopsies from the primary tumor, which may not adequately capture the well-known intratumoral and intertumoral heterogeneity in gastric cancer, potentially affecting interpretation of results and therapeutic decision-making. ERBB2 status was not evaluated by central pathology review; instead, assessment relied on local pathologists whose varying levels of expertise in ERBB2-low subclassification may have introduced additional variability. The study population comprised Turkish and Spanish patients, so generalizability of findings to other ethnic or geographic populations may be limited. Molecular analyses beyond immunohistochemistry and in situ hybridization, such as next-generation sequencing, were not performed, limiting the ability to explore the biological landscape of ERBB2-low tumors in greater depth.

DISCLOSURES

Terán disclosed receiving personal fees from Bristol Myers Squibb, Jazz Pharmaceuticals, BeOne Medicines, AstraZeneca, Astellas Pharma, and Merck Sharp & Dohme outside the submitted work. Pau Mascaró Baselga disclosed receiving travel reimbursement from Amgen, Eli Lilly and Company, Pierre Fabre, ROVI, LEO Pharma, Ferrer, and Servier. No other disclosures were reported by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.