Abstract
Although Fibroblast growth factor receptor (FGFR) 2 gene amplification and its prognostic significance have been reported in resectable gastric cancers, information on these features remains limited in the metastatic setting. The presence of FGFR2 amplification was assessed in formalin-fixed, paraffin-embedded tissues using a quantitative PCR-based gene copy number assay with advanced gastric cancer cohorts. A total of 327 patients with tumor portion of ≥70% were analyzed for clinical features. Among these patients, 260 who received first-line fluoropyrimidine and platinum chemotherapy were analyzed for survival.Sixteen of 327 patients (4.9%) exhibited FGFR2 amplification. The amplification group showed associations with age <65 years, Borrmann type 4 disease, poor performance status, poorly differentiated histology, extra-abdominal lymph node metastases, and bone metastases. The median overall survival (OS) and progression-free survival (PFS) were found to be 12.7 and 5.8 months, respectively. In univariate analysis, PFS did not differ between amplification and no amplification groups (hazard ratio [HR]=1.34, 95% confidence interval [CI]: 0.78-2.31, p=0.290), although the OS was significantly shorter in the amplification group (HR=1.92, 95% CI: 1.13-3.26, p=0.015). However, multivariate analysis indicated that FGFR2 amplification was not an independent prognostic factor for OS (HR=1.42, 95% CI: 0.77-2.61, p=0.261).Although FGFR2 amplification is associated with poorer OS, it does not appear to be an independent prognostic predictor in patients with advanced gastric cancer treated with palliative fluoropyrimidine and platinum chemotherapy.
Highlights
The prognosis of advanced gastric cancer has improved after introduction of cytotoxic chemotherapy [1], gastric cancer remains one of the leading causes of cancer-related death worldwide [2, 3]
We aimed to investigate the association of FGFR2 amplification with the clinicopathologic features and prognostic significance in patients with unresectable gastric cancer treated with fluoropyrimidine and platinum (FP) as first-line chemotherapy
We determined the presence of FGFR2 amplification by using the quantitative polymerase chain reaction (qPCR)-based gene copy number assay, and www.impactjournals.com/oncotarget
Summary
The prognosis of advanced gastric cancer has improved after introduction of cytotoxic chemotherapy [1], gastric cancer remains one of the leading causes of cancer-related death worldwide [2, 3]. The combination of trastuzumab with chemotherapy in HER2-positive advanced gastric cancer patients as first-line therapy and the addition of ramucirumab to taxane in non-selective advanced gastric cancer patients as second-line therapy exhibited modest survival benefits [10, 11], whereas other targeted agents, including bevacizumab, everolimus, and cetuximab, did not show overall survival gain without the use of biomarker enrichment strategies [12,13,14]. Despite these efforts to improve survival in gastric cancer, most patients with advanced gastric cancer usually have a median overall survival (OS) of < 12 months. A considerable amount of research is required to discover novel treatment targets for patients with advanced gastric cancer
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