Clinical characteristics and outcome of patients with combined hepatocellular-cholangiocarcinoma—a European multicenter cohort

There is no clear consensus on the optimal systemic treatment regimen in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients. We describe clinical characteristics and outcome of cHCC-CCA patients, with a special focus on patients receiving palliative systemic therapy, including immune checkpoint inhibitors (ICIs). In this European retrospective, multicenter study, patients with histologically proven cHCC-CCA treated at four institutions between April 2003 and June 2022 were included. In patients receiving palliative systemic therapy, outcome was compared between cytotoxic chemotherapy (CHT)- and non-cytotoxic CHT (nCHT)-treated patients. Of 101 patients, the majority were male (n = 70, 69%) with a mean age of 64.6 ± 10.6 years. Only type of first-line treatment was independently associated with overall survival (OS). Palliative systemic therapy was administered to 44 (44%) patients. Of those, 25 (57%) patients received CHT and 19 (43%) had nCHT (n = 16 of them sorafenib) in systemic first line. Although there was no significant difference in overall response rate (ORR; CHT versus nCHT: 8% versus 5%), disease control rate (24% versus 21%), and median progression-free survival {3.0 months [95% confidence interval (CI) 1.4-4.6 months] versus 3.2 months (95% CI 2.8-3.6 months), P = 0.725}, there was a trend towards longer median OS in the CHT group [15.5 months (95% CI 8.0-23.0 months) versus 5.3 months (95% CI 0-12.5 months), P = 0.052]. However, in multivariable analysis, type of first-line regimen (CHT versus sorafenib) was not associated with OS. ORR in patients receiving ICIs (n = 7) was 29%. In patients with cHCC-CCA, OS, progression-free survival, ORR, and disease control rate were not significantly different between individuals receiving CHT and patients receiving nCHT. Immunotherapy may be effective in a subset of patients. Prospective studies are needed to identify optimal systemic treatment regimens in cHCC-CCA. •There is no optimal systemic treatment regimen for patients with cHCC-CCA.•In this retrospective, multicenter cohort we describe clinical characteristics and outcome of 101 cHCC-CCA patients.•Whereas PFS, ORR, and DCR were similar, OS trended to be longer in patients treated with first-line CHT vs. non-cytotoxic CHT (mainly sorafenib), but type of first-line regimen (CHT versus sorafenib) was not associated with OS in multivariable analysis.•Treatment with ICIs may be effective in a subset of cHCC-CCA patients (ORR of 29%).