Pattern of progression of intrahepatic cholangiocarcinoma: Implications for second-line clinical trials

Francesco Tovoli, Ingrid Garajová, Fabio Gelsomino, Massimo Iavarone, Piera Federico, Massimiliano Salati, Matilde Corianò, Francesco Caputo, Stefania De Lorenzo, Alessandro Granito, Matteo Renzulli, Bruno Daniele, Fabio Piscaglia

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent liver cancer. The overall survival of iCCA and other biliary tract cancers (BTC) remains poor. Recently, the ABC-06 trial reported the superiority of FOLFOX vs clinical observation as a second-line treatment. Still, the survival benefit was less than expected. We hypothesized that the pattern of progression of iCCA can drive post-progression survival (PPS), similar to hepatocellular carcinoma. Methods: Multicentre retrospective evaluation of consecutive iCCA patients who progressed after frontline systemic treatment with gemcitabine as monotherapy or in combination with platinum. Radiological assessment of progression was evaluated according to RECIST 1.1. The progression pattern was divided according to the presence/absence of new extrahepatic lesions (NEH). Results: We included 206 patients from 5 centres. The median OS was 14.1 months and its independent predictors (hazard ratio [HR], 95% confidence interval [CI]) were previous surgery 0.699 [0.509-0.961], performance status >2.445 [1.788-3.344], permanent first-line discontinuation 16.072 [5.102-50.633], registration of ascites 2.226 [1.448-3.420] or bilirubin >3 mg/dl 3.004 [1.935-4.664] during the follow-up, and disease progression 2.523 [1.261-5.050]. The appearance of NEH independently predicted OS 2.18 [1.55-3.06] in patients with radiological progression. Amongst 138 patients eligible for second-line treatment, PPS was 16.8 and 5.9 months in cases without and with NEH, respectively (P =.001). Progression owing to NEH lesions was an independent predictor of PPS 1.873 [1.333-2.662], together with performance status, time to progression to the frontline treatment, bilirubin >3 mg/dl and ascites. Conclusions: PPS of iCCA is influenced by progression pattern, with important implications for second-line trial design and analysis.

Original languageEnglish
Pages (from-to)458-467
JournalLiver International
Volume42
Issue number2
DOIs
Publication statusPublished - 2022

Keywords

  • biliary tract cancer
  • cholangiocarcinoma
  • liver cancer
  • outcome
  • prognosis

ASJC Scopus subject areas

  • Hepatology

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