Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2020 Jan 1;6(1):51-59.
doi: 10.1001/jamaoncol.2019.3702.

Radioembolization Plus Chemotherapy for First-line Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial

Julien Edeline  1   2 , Yann Touchefeu  3 , Boris Guiu  4 , Olivier Farge  5 , David Tougeron  6 , Isabelle Baumgaertner  7 , Ahmet Ayav  8 , Boris Campillo-Gimenez  1   9 , Luc Beuzit  10 , Marc Pracht  1 , Astrid Lièvre  11   12 , Samuel Le Sourd  1 , Karim Boudjema  13 , Yan Rolland  14 , Eveline Boucher  1 , Etienne Garin  15
Affiliations
Clinical Trial

Radioembolization Plus Chemotherapy for First-line Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial

Julien Edeline et al. JAMA Oncol. .

Abstract

Importance: Patients 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.

Objective: To determine the response rate after SIRT combined with chemotherapy in patients with unresectable ICC.

Design, setting, and participants: This 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.

Interventions: Concomitant 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 measures: Response 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.

Results: Of 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 relevance: Combination 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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Edeline reported acting as a consultant and receiving grants and personal fees from BTG Corporation during the conduct of the study; receiving personal fees from AstraZeneca, Bristol-Myers Squibb Company, EISAI Company Ltd, IPSEN Pharma, Merck Sharp and Dohme Corporation, and receiving nonfinancial support from Amgen Inc outside the submitted work. Dr Touchefeu reported receiving Therasphere supplied by BTG Corporation. Dr Guiu reported receiving personal fees from BTG Corporation during the conduct of the study, receiving grants and personal fees from Boston Scientific Corporation and Guerbet LLC, and receiving personal fees from Angiodynamics Inc, Canon, Quantum Surgical, and Terumo Corporation outside the submitted work. Dr Tougeron reported receiving personal fees and travel support from AstraZeneca, Merck Sharp and Dohme Corporation, and Roche; receiving personal fees from Sanofi and Servier; and receiving travel support from Amgen Inc and BTG Corporation outside the submitted work. Dr Campillo-Gimenez reported receiving grants and nonfinancial support from Biocompatibles UK Limited during the conduct of the study. Dr Beuzit reported receiving nonfinancial support from BTG Corporation during the conduct of the study. Dr Lièvre reported receiving nonfinancial support from BTG Corporation during the conduct of the study; receiving personal fees and nonfinancial support from Advanced Accelerator Applications, Bayer, Ipsen, Merck, Roche, and Servier; receiving personal fees from Amgen, Bristol-Myers Squibb Company, Celgene, HalioDX, Incyte, Eli Lilly and Company, and, Sandoz; receiving grants, personal fees, and nonfinancial support from Novartis; and receiving nonfinancial support from Pfizer outside the submitted work. Dr Rolland reported acting as a consultant and receiving personal fees from BTG Corporation outside the submitted work. Dr Boucher reported acting as a consultant and is presently employed by BTG Corporation. Dr Garin reported acting as a consultant and receiving grants from Ligue Against Cancer during the conduct of the study and receiving grants, personal fees, and nonfinancial support from BTG Corporation UK Ltd outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart
ECOG indicates Easter Cooperative Oncology Group; RECIST, Response Evaluation Criteria in Solid Tumors.
Figure 2.
Figure 2.. Best Response for Target Lesions by Patient by Central Review
RECIST indicates Response Evaluation Criteria in Solid Tumors.
Figure 3.
Figure 3.. Progression-Free, Overall, and Relapse-Free Survival
A and B, Overall (A) and progression-free (B) survival in all patients in the intent-to-treat population. C and D, Overall (C) and relapse-free (D) survival among the 9 patients who underwent resection starting on the date of surgery.
See this image and copyright information in PMC

Comment in

References

    1. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States part III: liver, biliary tract, and pancreas. Gastroenterology. 2009;136(4):1134-1144. doi:10.1053/j.gastro.2009.02.038 - DOI - PubMed
    1. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383(9935):2168-2179. doi:10.1016/S0140-6736(13)61903-0 - DOI - PMC - PubMed
    1. Valle J, Wasan H, Palmer DH, et al. ; ABC-02 Trial Investigators . Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273-1281. doi:10.1056/NEJMoa0908721 - DOI - PubMed
    1. Okusaka T, Nakachi K, Fukutomi A, et al. . Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010;103(4):469-474. doi:10.1038/sj.bjc.6605779 - DOI - PMC - PubMed
    1. Valle JW, Furuse J, Jitlal M, et al. . Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of 2 randomised trials. Ann Oncol. 2014;25(2):391-398. doi:10.1093/annonc/mdt540 - DOI - PubMed

Publication types

LinkOut - more resources