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.
Campani et al. (2026) studied this question.