Acquired FGFR2 mutation leads resistance to pemigatinib in a patient with FGFR2-driven Borrmann type IV gastric cancer.
Qiong Sun, Sicheng Du, Jing Meng et al.
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Case in brief
A 47-year-old woman with advanced, chemotherapy-refractory Borrmann type IV gastric cancer had FGFR2 rearrangement and amplification. Pemigatinib, a selective FGFR1–3 inhibitor, produced a marked clinical and serological response, but the cancer progressed after 3 months. Genomic profiling at progression identified an acquired FGFR2 N549K mutation, a recognized on-target resistance mechanism. After she received the irreversible FGFR1–4 inhibitor futibatinib, tumor biomarkers showed a declining trend, suggesting preliminary antitumor activity against the resistant clone.
What made this case unusual
The case documents acquired FGFR2 N549K mutation at progression on pemigatinib in Borrmann type IV gastric cancer, followed by a declining tumor-biomarker trend with futibatinib.
Diagnostic / clinical pearl
At progression on FGFR-directed therapy, genomic profiling may identify an acquired kinase-domain resistance mutation, as in this case, and help characterize the resistant clone.
Why it matters
The biomarker trend after futibatinib suggests possible activity against the resistant clone, but the authors note that this strategy warrants further clinical investigation.