Dataset Information

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

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.

SUBMITTER: Tovoli F

PROVIDER: S-EPMC9300150 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Tovoli Francesco F Garajová Ingrid I Gelsomino Fabio F Iavarone Massimo M Federico Piera P Salati Massimiliano M Corianò Matilde M Caputo Francesco F De Lorenzo Stefania S Granito Alessandro A Renzulli Matteo M Daniele Bruno B Piscaglia Fabio F

Liver international : official journal of the International Association for the Study of the Liver 20211210 2

<h4>Background</h4>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.<h4>Methods</h4>Mu ...[more]

PMID: 34826193

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Project description:ImportancePatients with unresectable intrahepatic cholangiocarcinoma (ICC) have a poor prognosis. Selective internal radiotherapy (SIRT) is a promising treatment option for hepatic tumors, but no prospective studies of combination SIRT with chemotherapy have been published to our knowledge.ObjectiveTo determine the response rate after SIRT combined with chemotherapy in patients with unresectable ICC.Design, setting, and participantsThis phase 2 clinical trial, the Yttrium-90 Microspheres in Cholangiocarcinoma (MISPHEC) trial, included patients with unresectable ICC who have never received chemotherapy or intra-arterial therapy and were treated at 7 centers which had experience with SIRT between November 12, 2013, and June 21, 2016. Statistical analysis was performed from March 31, 2017, to June 17, 2019.InterventionsConcomitant first-line chemotherapy with cisplatin, 25 mg/m2, and gemcitabine, 1000 mg/m2 (gemcitabine reduced to 300 mg/m2 for the cycles just before and after SIRT), on days 1 and 8 of a 21-day cycle for 8 cycles. Selective internal radiotherapy was administered during cycle 1 (1 hemiliver disease) or cycles 1 and 3 (disease involving both hemilivers) using glass Y90 microspheres.Main outcomes and measuresResponse rate at 3 months according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary end points were toxic effects, progression-free survival, overall survival, disease control rate, and response rate according to Choi criteria.ResultsOf 41 patients included in the study, 26 (63%) were male, with a mean (SD) age of 64.0 (10.7) years. Response rate according to RECIST was 39% (90% CI, 26%-53%) at 3 months according to local review and was confirmed at 41% as best response by central review; disease control rate was 98%. According to Choi criteria, the response rate was 93%. After a median follow-up of 36 months (95% CI, 26-52 months), median progression-free survival was 14 months (95% CI, 8-17 months), with progression-free survival rates of 55% at 12 months and 30% at 24 months. Median overall survival was 22 months (95% CI, 14-52 months), with overall survival rates of 75% at 12 months and 45% at 24 months. Of 41 patients, 29 (71%) had grades 3 to 4 toxic effects; 9 patients (22%) could be downstaged to surgical intervention, with 8 (20%) achieving R0 (microscopic-free margins) surgical resection. After a median of 46 months (95% CI, 31 months to not reached) after surgery, median relapse-free survival was not reached among patients who underwent resection.Conclusions and relevanceCombination chemotherapy and SIRT had antitumor activity as first-line treatment of unresectable ICC, and a significant proportion of patients were downstaged to surgical intervention. A phase 3 trial is ongoing.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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