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

BACKGROUND: 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). METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.