Genomic Profiling Reveals Impact of Immunotherapy in Patients With IDH1+ and FGFR2+ Metastatic Biliary Tract Cancer

A recent study presented at the 2025 ASCO Gastrointestinal Cancers Symposium highlighted the significance of comprehensive genomic profiling (CGP) in guiding treatment decisions for patients with metastatic biliary tract cancer (mBTC). The study, which analyzed real-world data from GuardantINFORM, indicated that patients with IDH1 mutations (IDH1+) or fibroblast growth factor receptor 2 (FGFR2) fusions (FGFR2+) may experience worse outcomes when immunotherapy (IO) is added to first-line gemcitabine-cisplatin (GemCis) treatment.

This real-world study aimed to examine survival outcomes in patients with mBTC receiving GemCis alone or GemCis plus IO following circulating tumor DNA (ctDNA)-detected IDH1 mutations (IDH1+) or FGFR2 fusions (FGFR2+). Patients with mBTC (all cholangiocarcinoma) who were identified as IDH1+ or FGFR2+ through ctDNA testing between April 2019 and June 2024 were included in the study. Only patients treated with first-line GemCis or GemCis plus IO were considered for survival analysis. For IDH1+ patients, second-line therapy with either ivosidenib or another treatment was also evaluated. Real-world time to treatment discontinuation (rwTTD) and real-world time to next treatment (rwTTNT) were used as proxies for progression-free survival, while real-world overall survival (rwOS) was assessed in months.

Of 4840 mBTC patients identified through claims data, 412 were IDH1+ and 154 were FGFR2+. In IDH1+ patients, 38.1% received first-line GemCis while 25.7% received GemCis plus IO. In the FGFR2+ group, 45.5% received first-line GemCis and 28.6% received GemCis plus IO. The results demonstrated that, in the IDH1+ cohort, patients treated with GemCis alone had improved rwOS compared with those treated with GemCis plus IO, with a median rwOS of 30 months versus 16 months, respectively (P<.001). Similarly, in the FGFR2+ cohort, patients receiving GemCis alone had better rwOS compared with those receiving GemCis plus IO (not reached vs 43 months, respectively; P=.005). There were no significant differences in rwTTNT or rwTTD in either the IDH1+ or FGFR2+ cohorts for patients receiving GemCis or GemCis plus IO. Furthermore, among all patients receiving GemCis plus IO, those without IDH1 mutations had numerically better rwOS compared with those with IDH1 mutations. However, no survival difference was observed between IDH1+ and non-IDH1+ patients receiving GemCis alone. In patients who were FGFR2+, rwOS was similar to FGFR2– patients when treated with GemCis plus IO; however, outcomes were improved when treated with GemCis alone.

These findings suggest that adding IO to GemCis may not be beneficial for patients with mBTC with IDH1+ or FGFR2+ alterations and may, in fact, lead to decreased overall survival. The study supports the use of ctDNA CGP to inform clinical decision-making before starting first-line therapy and emphasizes the potential of liquid biopsy as a rapid, noninvasive method for identifying these specific genomic alterations. These results suggest that personalized treatment strategies based on genomic profiling may improve outcomes for mBTC patients.

Source:

Kim R, Lewis C, Bubie A, et al. Real-world survival differences in advanced biliary tract patients with ctDNA detected IDH1 mutations and FGFR2 fusions receiving first-line gemcitabine-cisplatin with and without immunotherapy. Presented at: ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025; San Francisco, CA; Virtual. Poster 548.