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Loss of ERRFI1 function in biliary tract cancers (BTCs) may predict response to EGFR-targeted therapy. This study found ERRFI1 mutations are actionable biomarkers, showing clinical benefit in pretreated BTC patients.

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • EGFR alterations are common in biliary tract cancers (BTCs), correlating with poor prognosis.
  • Targeted therapies for EGFR alterations in BTC are underexplored.
  • ERRFI1, an EGFR inhibitor, is frequently mutated in BTC, suggesting its potential as a predictive biomarker.

Purpose of the Study:

  • To investigate if loss of ERRFI1 function enhances sensitivity to EGFR-targeted tyrosine kinase inhibitors (TKIs).
  • To explore ERRFI1 mutations as potential predictive biomarkers for EGFR-TKI therapy in BTC.

Main Methods:

  • Retrospective multicenter study of 14 BTC patients with ERRFI1 alterations.
  • Analysis of ERRFI1 alteration types, variant allele frequencies, and coalterations.
  • Evaluation of treatment outcomes, including response, time to progression (TTP), overall survival (OS), and safety profiles.

Main Results:

  • Common coalterations included IDH1, TP53, and ARID1A.
  • Eight patients received EGFR TKIs, with 3 partial responses (2 >20 months) and 4 stable diseases.
  • Median TTP was 7 months, median OS was 20 months, with good tolerability.

Conclusions:

  • ERRFI1 mutations are actionable biomarkers in BTC.
  • EGFR-targeted therapy shows clinical benefit in BTC patients with ERRFI1 mutations.
  • Routine ERRFI1 testing is recommended for BTC molecular profiling.