Study: FGFR mRNA Overexpression Occurs Frequently for Those With Cholangiocarcinoma

Investigators also confirmed that FGFR2 fusion–positive tumors have a higher expression of FGFR2 but were not associated with higher expression of FGFR1, FGFR3, or FGFR4.

In the absence of genetic alterations in the FGFR gene, FGFR mRNA overexpression can occur frequently in individuals with cholangiocarcinoma, according to the results of a study published in Clinical Cancer Research.

Investigators concluded that further investigation of FGFR inhibitors is needed, outside approved indications.

Investigators included individuals who underwent surgical resection for cholangiocarcinoma but did not undergo neoadjuvant therapy at Massachusetts General Hospital between 2004 and 2015.

A second cohort comprised individuals with advanced FGFR2 fusion–positive or rearrangement-positive cholangiocarcinoma treated with at least 1 selective FGFR inhibitor. They were included to determine a correlation between the baseline FGFR mRNA expression and response to FGFR inhibitor.

The individuals were diagnosed with cholangiocarcinoma between May 2015 and May 2019 and were treated as part of the clinical trial.

Investigators analyzed data from 94 individuals, with 77% having intrahepatic cholangiocarcinoma (ICC) and the remaining having extrahepatic cholangiocarcinoma (ECC). The individuals’ tumors were spread across all 4 stages.

Investigators found the FGFR2 fusions were found in 23% of ICCs and 5% of ECCs. They also confirmed that FGFR2 fusion–positive tumors had a higher expression of FGFR2 but were not associated with higher expression of FGFR1, FGFR3, or FGFR4.

In individuals who were FGFR2 fusion­–negative, there were high expressions for all 4 genes, and 62% of fusion–negative cholangiocarcinoma had high levels of FGFR mRNA expression.

Investigators also found that in the 17 individuals with FGFR2 fusion­–positive ICC, 70% had high levels of FGFR2 mRNA expression, with the remaining having low levels. The individuals with FGFR2 fusion­–positive ECC had low FGFR2 mRNA expression.

Among 13 individuals with FGFR2 fusion–positive cholangiocarcinoma, prior to treatment with an inhibitor, who were treated with futibatinib, 38% had high levels of FGFR2 mRNA expression, 54% had low levels, and 7% had no detectable expression. Investigators reported that the overall response rate in the high-expressor group was 22%, with a progression-free survival of 11 months, while the low-expressor group was 33% and 7 months.

Investigators concluded that FGFR2 fusion status and FGFR2 mRNA expression levels did not significantly affect recurrence rates or relapse-free survival in individuals with either ICC or ECC.

The median overall survival (OS) for the entire cohort was 35.2 months, with individuals in the ICC group having significantly higher OS at 44.2 months compared with those in the ECC group at 18.2 months.

Investigators reported that there were no significant differences in OS between FGFR2 fusion­–negative or positive individuals with ICC. Additionally, there was no difference for individuals with ICC whose tumors had high or low FGFR2 mRNA expression.

The study included limitations, such as unknown FGFR mutation, as well as amplification status. The investigators were also limited by the number of individuals with FGFR2 fusion–positive cholangiocarcinoma treated with FGFR inhibitors who had sufficient residual biopsy material. Additionally, the study had a small population of those with ECC; therefore, most of the results were based on the ICC analysis.

Reference

Sridharan V, Neyaz A, Chougule A, Baiev I, et al. FGFR mRNA expression in cholangiocarcinoma and its correlation with FGFR2 fusion status and immune signatures. Clin Cancer Res. 2022;CCR-22-1244. doi:10.1158/1078-0432.CCR-22-1244