Liver Cancer (Jun 2022)

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

  • Elia Gigante,
  • Christian Hobeika,
  • Brigitte Le Bail,
  • Valérie Paradis,
  • David Tougeron,
  • Marie Lequoy,
  • Mohamed Bouattour,
  • Jean-Frederic Blanc,
  • Nathalie Ganne-Carrié,
  • Henri Tran,
  • Clémence Hollande,
  • Manon Allaire,
  • Giuliana Amaddeo,
  • Hélène Regnault,
  • Paul Vigneron,
  • Maxime Ronot,
  • Laure Elkrief,
  • Gontran Verset,
  • Eric Trepo,
  • Aziz Zaanan,
  • Marianne Ziol,
  • Massih Ningarhari,
  • Julien Calderaro,
  • Julien Edeline,
  • Jean-Charles Nault

DOI
https://doi.org/10.1159/000525488

Abstract

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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.