Outcome of Metastatic Biliary Tract Cancer Harbouring IDH1 or FGFR2 Alterations: A Retrospective Observational Real-World Study from a French Cohort

TL;DR

This study found that patients with metastatic biliary tract cancer and specific genetic changes (IDH1 or FGFR2) had better survival than those without these changes, but the benefit may come from targeted therapies.

Contribution

The study provides real-world evidence on the prognostic value of IDH1 and FGFR2 alterations in metastatic biliary tract cancer.

Findings

Patients with IDH1 or FGFR2 alterations had a median overall survival of 24.2 months compared to 10.8 months for wild-type tumors.

The hazard ratio for death was 0.46 for patients with IDH1 or FGFR2 alterations, indicating a survival benefit.

There was no difference in progression-free survival for first-line treatment between the groups.

Abstract

Background: Biliary tract cancer (BTC) management has undergone tremendous changes, benefiting from the identification of highly actionable molecular alterations. Among these, IDH1 mutations and FGFR2 fusions are the most common alterations detected and are classified as ESCAT tier 1 in BTC. However, their prognostic value in real-world settings remains uncertain. Objective: To explore overall survival (OS) in patients harbouring locally advanced or metastatic BTC (mBTC) with IDH1 or FGFR2 alterations, compared to those with wild-type tumours. Methods: This retrospective, multicentre study included patients with mBTC treated between 2020 and 2023 across five French centres. Patients were categorized into two cohorts based on molecular profiling: those with IDH1 or FGFR2 alterations, and those with wild-type tumours (WT-mBTC). Results: 119 consecutive patients were included. 18 were classified as altered (IDH1 = 13; FGFR2 = 5). Sixty-four pts underwent no molecular testing. The median OS of the entire cohort was 11.9 months (10.3–14.3). The median OS was 24.2 months (12.3–NA) versus 10.8 months (7.9–12.9), p = 0.02, in the altered and WT-mBTC cohorts, respectively. The Cox regression model conducted depicted an HR for death of 0.46 (CI95%, 0.2–0.9) for IDH1 or FGFR2 alterations. There were no diffence in PFS for first-line. Conclusions: Our cohort suggests that IDH1 or FGFR2 alterations may be associated with prognostic differences in patients with metastatic BTC, although they do not appear to influence outcomes under first-line treatment. These findings are consistent with trends observed in clinical trials. Whether improved survival is solely attributable to targeted therapies remains questionable. In line with ESMO recommendations, systematic molecular profiling should be considered in patients with mBTC.

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