Clinico-molecular characteristics and enhanced efficacy of immune checkpoint inhibitors in TP53-mutated advanced biliary tract cancer - PubMed

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TP53 mutations are prevalent in biliary tract cancer (BTC), with 52.7% of patients in the study having TP53-mutated tumors in the tissue-based cohort.
The study identifies unique molecular profiles: TP53-mutated tumors are enriched with co-alterations like SMAD4, ERBB2, PTEN, and CCNE1, while wild-type tumors more frequently have IDH1, BAP1, and FGFR2 fusions.
TP53 mutations are independently associated with shorter progression-free survival (PFS) and show a trend toward shorter overall survival (OS), indicating a poorer prognosis.
A significant treatment-TP53 interaction is observed: TP53 mutations correlate with shorter PFS in non-ICI regimens but numerically longer PFS in ICI-containing regimens, suggesting enhanced efficacy of immune checkpoint inhibitors.
Transcriptomic analysis reveals lower TIDE scores in TP53-mutated tumors, implying these tumors may be more responsive to immunotherapy due to reduced immune evasion potential.
The findings support biomarker-driven stratification in advanced BTC, proposing TP53 mutations as a predictor for greater benefit from ICI therapy.

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