‘FGFR2b’ draws interest as a new biomarker for gastric cancer treatment

Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein is attracting attention as a new biomarker in treating gastric cancer.

According to a recent paper published by Professor Rha Sun-young of the Department of Medical Oncology at Yonsei Cancer Center in JCO Precision Oncology, an international journal of the American Society of Clinical Oncology (ASCO), 37.8 percent of patients with advanced or metastatic gastric cancer and gastroesophageal junction cancer were overexpressing FGFR2b protein.

The finding was based on an analysis of pre-screening data from a global phase 3 clinical trial in gastric cancer patients (the FORTITUDE-101 study), which measured FGFR2b protein expression by immunohistochemistry (IHC) staining using tumor samples from 3,782 patients.

“This study provides an important foundation that could dramatically change the treatment approach for patients with gastric cancer,” Professor Rha said, evaluating her findings.

The study was a large global analysis of gastric cancer patients from 287 medical institutions in 37 countries to determine the prevalence of FGFR2b protein overexpression.

The researchers used the IHC-based VENTANA FGFR2b (FPR2-D) RxDx Assay developed by Roche Diagnostics to assess FGFR2b protein overexpression. To reduce the variation in test results between institutions, the samples were tested in batches at a centralized laboratory, and each sample was read by pathologists experienced in IHC evaluation.

The results showed that 37.8 percent (1,428 among 3,782) of subjects overexpressed FGFR2b protein, and 16.2 percent (612 among 3782) of them were found to overexpress FGFR2b protein in more than 10 percent of tumor cells.

“The proportion of FGFR2b protein overexpression did not differ significantly within characteristics, such as patient age, gender, sampling method (biopsy vs. resection), sampling site, location of the primary tumor, or region,” the researchers added.

This showed that FGFR2b expression is not limited to specific populations or regions and likely has a consistent prevalence worldwide.

The findings strongly suggest that the FGFR2b protein may be a novel target in treating advanced or metastatic gastric cancer.

Currently, the HER2 protein is the leading biomarker in treating gastric cancer, and targeted therapy, including trastuzumab, is the standard of care for patients with HER2-positive gastric cancer.

More recently, the Claudin 18.2 protein, which is expressed in about 40 percent of gastric cancer patients, has been proposed as a new target, and a targeted antitumor drug (zolbetuximab) has been developed, opening new horizons in the HER2-negative patient group.

FGFR2b protein is also an independent biomarker distinct from HER2 that may offer new treatment options in the HER2-negative population.

However, further research is needed to establish FGFR2b protein as a therapeutic biomarker for gastric cancer.

“We need to analyze further whether FGFR2b protein overexpression directly correlates with patient survival and how it relates to other biomarkers,” the researchers emphasized. “Further studies are also needed to determine how FGFR2b protein changes at different stages of gastric cancer progression and whether there are differences in expression between primary and metastatic tumors.”

According to experts, the FGFR2b protein is gaining traction because therapies are being developed to target it.

One of these is bemarituzumab, a monoclonal antibody currently in development by Amgen. In a previous phase 2 trial (the FIGHT study), it was shown that, when combined with chemotherapy, it significantly improved survival in patients with FGFR2b overexpression.

In the FORTITUDE-101 study, a global phase 3 clinical trial, the effect of bemarituzumab plus chemotherapy (mFOLFOX6) is being evaluated compared to placebo plus chemotherapy in patients who overexpress FGFR2b protein by 10 percent or more.

If the results of the FORTITUDE-101 study are positive, bemarituzumab could become the new standard of care for gastric cancer as a first-in-class targeted antitumor agent that targets the FGFR2b protein.

All this explains why experts are interested in seeing if FGFR2b can open a new paradigm in treating advanced or metastatic gastric cancer.