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Supplementary Material for: Systemic treatments with tyrosine kinase inhibitor and platinum-based chemotherapy in patients with unresectable or metastatic hepatocholangiocarcinoma

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posted on 14.06.2022, 14:49 authored by Gigante E., Hobeika C., LeBail B., Paradis V., Tougeron D., Lequoy M., Bouattour M., Blanc J.F., Ganne-Carrié N., Tran H., Hollande C., Allaire M., Amaddeo G., Regnault H., Vigneron P., Ronot M., Elkrief L., Verset G., Trepo E., Zaanan A., Ziol M., Ningarhari M., Calderaro J., Edeline J., Nault J.C.
Backgrounds and aims: Even if no systemic treatment is currently validated for unresectable hepato-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKI), and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA. Patients and Methods: Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (n=117) and with intrahepatic cholangiocarcinoma (iCCA, n=94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of tyrosine kinase inhibitors and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator. Results: A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%)(p <0.001). Both HCC (36.8% and cHCC-CCA (66.2%) had less frequent extrahepatic metastases than iCCA (81%)(P<0.001). Unadjusted overall survival (OS) was better in iCCA (13 months) compared to cHCC-CCA (12 months) and HCC (11 months) (p=0.130). In multivariable analysis, after adjustment by a Cox frailty model, patients with cHCC-CCA had the same survival as HCC and iCCA (HR=0.67, CI95%:0.37-1.22, p=0.189 and HR=0.66, CI95%:0.43-1.02, p=0.064 respectively). ALBI score (HR=2.15; CI95%:1.23-3.76; p=0.009), ascites (HR=3.45, CI95%:1.31-9.03, p=0.013) and tobacco use (HR=2.29, CI95%:1.08-4.87, p=0.032) were independently associated with OS in cHCC-CCA. Among patients with cHCC-CCA, 25 patients treated with TKI were compared with 54 patients who received platinum-based chemotherapies. Patients treated with TKI had a median OS of 8.3 months compared to 11.9 months for patients treated with platinum-based chemotherapy (p=0.86). After a robust doubly adjustment on tumor number and size, vascular invasion, ALBI, MELD, and cirrhosis, the type of treatment did not impact OS (HR=0.92, 95%CI:0.27-3.15, p=0.88) or progression-free survival (HR=1.24, 95%CI:0.44-3.49, p=0.67). Conclusions: First-line systemic treatments with tyrosine kinase inhibitors or platinum-based chemotherapies have similar efficacy in patients with unresectable/metastatic cHCC-CCA. The ALBI score predicts overall survival.

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