Despite identifying resistance mutations, evidence is insufficient to definitively link a specific alteration to a subsequent drug's efficacy. Biomarkers provide crucial context for clinicians, but do not yet dictate a precise treatment path, highlighting the need for clinical judgment.
Early studies found FGFR2 fusions in ~15% of patients, skewed by testing heavily pre-treated individuals. As testing moves to the first-line setting, the true prevalence appears to be much lower (5-8%), which has major implications for clinical trial design and prevalence estimates.
Clinicians must recognize that not all genomic tests are adequate for identifying FGFR2 fusions. Amplicon-based NGS panels are not suitable for this purpose. RNA-based sequencing is the recommended approach to avoid missing patients who could benefit from targeted FGFR inhibitors.
While re-biopsy at progression is useful, ctDNA (liquid biopsy) offers a distinct advantage by detecting multiple concurrent resistance mechanisms (polyclonal resistance). This provides a more comprehensive picture of tumor heterogeneity than a single tissue biopsy, better informing subsequent treatment choices.