What question did this study set out to answer?

The research aims to identify actionable genomic alterations in advanced primary liver cancers resistant to standard therapy.

March 23, 2026Open Access

Molecularly guided therapies for advanced primary liver cancers refractory to systemic treatment: Results from the 2025 French Genomic Medicine Initiative

Puntos clave

The research aims to identify actionable genomic alterations in advanced primary liver cancers resistant to standard therapy.
Enrolled patients with advanced primary liver cancers progressing on systemic therapy across eight centers.
Analyzed tumor and blood samples using whole-genome, whole-exome, and RNA sequencing.
Classified alterations according to the ESCAT scale and reviewed findings with a molecular tumor board.
120 patients enrolled, with various liver cancer types including HCC and CCA.
67 patients had at least one actionable alteration, with disease control observed in 32.3% of those treated.
Median progression-free survival was significantly longer in patients achieving disease control compared to those with progression.

Resumen

Background TP53 (55%), ARID1A (20%), and BAP1 in CCA; TP53 (67%), PIK3CA (22%), and ARID2 (11%) in cHCC-CCA.Among 103 interpretable genomes, 67 patients harbored at least one actionable alteration (HCC: 59%, CCA: 80%, cHCC-CCA: 78%).Thirty-one patients (22 HCC, 5 CCA, 3 cHCC-CCA, 1 HEHE, 1 HS) received matched therapies: 1 ESCAT I, 2 ESCAT II, 21 ESCAT III, and 7 ESCAT IV.These patients had received prior systemic therapy including two lines or more in 69% of the cases.Disease control (DC; radiological response/stable disease) was achieved in 10 of 31 patients (32.3%), including 23% of HCC, 75% of CCA, and 67% of cHCC-CCA cases.DC was observed exclusively in patients treated for ESCAT I-III alterations (41.7%), with no clinical benefit in those treated for ESCAT IV alterations.Median progression-free survival was significantly longer in patients achieving DC compared with those with progressive disease (11.8 vs. 2.4 months; p=0.009)Conclusions: Comprehensive genomic profiling in advanced PLC refractory to systemic treatments is feasible and associated with disease control in a subset of pretreated patients with ESCAT I/II/III alterations.

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