Circulating tumor DNA (ctDNA) analysis allows for early detection of resistance mechanisms, such as secondary FGFR2 mutations, before tumors show growth on scans. This provides a potential window to adjust treatment strategies proactively, offering an advantage over traditional imaging-based monitoring.
For extrahepatic cholangiocarcinoma, obtaining a sufficient tissue sample for diagnosis and molecular profiling can be extremely difficult. Circulating tumor DNA (ctDNA) testing, or liquid biopsy, serves as a crucial alternative in these cases, providing a non-invasive method to secure a diagnosis and identify actionable mutations when a traditional tissue biopsy is not feasible.
A real-world analysis of pemigatinib reported low rates of dose reduction or discontinuation. This may be misleading, as the toxicities of FGFR inhibitors (e.g., nail, skin, eye issues) are cumulative and worsen over extended periods. The study's shorter follow-up likely didn't capture the full long-term safety profile of the drug.
A real-world study found that 25% of patients on pemigatinib had extrahepatic cholangiocarcinoma, a subtype where the drug's FGFR2 fusion target is historically rare. This significant deviation from established biology suggests potential issues with physician-abstracted data, such as mislabeling or referral bias, highlighting the need for cautious interpretation of real-world patient cohorts.
Real-world data for pemigatinib in cholangiocarcinoma showed a higher response rate (59%) than the pivotal FITE-202 trial (36%). This discrepancy likely stems from the lack of standardized, centrally reviewed imaging in real-world settings, which can inflate perceived response. Comparable progression-free survival across both settings supports this interpretation.