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Whole-genome, exome and RNA sequencing through France's national genomics programme found a targetable change in about two-thirds of 103 interpretable liver cancers that had stopped responding to treatment; 31 patients got a matched drug and 10 had their disease controlled.
120 patients with primary liver cancer progressing on systemic therapy were enrolled across eight centres: 80 with hepatocellular carcinoma, 25 with cholangiocarcinoma, 9 with combined hepatocellular-cholangiocarcinoma, 4 with fibrolamellar carcinoma, 1 hepatic sarcoma and 1 epithelioid haemangioendothelioma. Tumour and blood were analysed by whole-genome, whole-exome and RNA sequencing through the PFMG2025 platforms, and results were reviewed by a molecular tumour board and graded on the ESCAT scale.
Of 103 interpretable genomes, 67 patients had at least one actionable alteration (59 per cent of hepatocellular carcinomas, 80 per cent of cholangiocarcinomas, 78 per cent of combined tumours). 31 patients received matched therapy, 69 per cent of them after two or more previous lines. Disease control was achieved in 10 of the 31 (32.3 per cent), only among patients treated for ESCAT I to III alterations (41.7 per cent), with no benefit from ESCAT IV matches; median progression-free survival was 11.8 months with disease control against 2.4 months with progression.
For liver cancers that have stopped responding, national genome sequencing found something to target in most patients, but only matches backed by stronger evidence (ESCAT I to III) helped. The authors say the combined sequencing found alterations beyond the reach of standard sequencing panels; the study did not test panels side by side.
Shares Pierre Laurent-Puig, PFMG2025: integrating genomic medicine into the national healthcare system in France.
Shares Next-generation sequencing (NGS), Biliary tract cancer (cholangiocarcinoma).
Shares Next-generation sequencing (NGS), Biliary tract cancer (cholangiocarcinoma).
Shares Next-generation sequencing (NGS), Biliary tract cancer (cholangiocarcinoma).
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