Initial results from the phase II randomized trial comparing TACE with irinotecan and mitomycin C to doxorubicin in intermediate stage HCC (IRITACE trial)

BackgroundTransarterial chemoembolisation (TACE) is the standard of care in patients with intermediate stage HCC. However, the choice of chemotherapeutic agents is not standardized and highly diverse. Evidence from preclinical data as well as early clinical data supported the evaluation of Irinotecan and Mitomycin C with embolization in patients with intermediate stage HCC.MethodsThe multicenter, randomized phase 2 trial included Barcelona Clinic Liver Cancer (BCLC B) stage HCC patients who were randomized 1:1 to receive Drug-eluting Beads (DEB)-TACE with Irinotecan and Mitmoycin C (Arm A) or DEB-TACE with Doxorubicin (Arm B). The primary end point was progression free survival (PFS) according to mRECIST criteria. Secondary end points included overall survival, response rate, safety, and quality of life. The trial was prematurely stopped due to insufficient accrual.ResultsFrom June 2020 until August 2022 20 patients in three centers were included into the trial and 17 patients could be analyzed for efficacy and safety. The median PFS was 9.2 months (Arm A) and 21.1 months (Arm B), respectively (P=0.63). 24 months survival were 67% (Arm A), and 57% (Arm), respectively (P= 0.59). 44% of patients in Arm A and 63% of patients in Arm B had a response to treatment. All grade and grade ≥3 toxicities were reported in 93% and 17% of patients in Arm A and in 79% and 43% of patients in Arm B, respectively.ConclusionsDEB-TACE with Irinotecan and Mitomycin C failed to show superior PFS compared to Doxorubcin based DEB-TACE. PFS and overall survival rates were higher than estimated. Still no evidence-based standard of care chemotherapeutic agent could be defined for TACE.Clinical trial identificationEudraCT: 2019-000922-23.Legal entity responsible for the studyDekanat des Fachbereichs Medizin Klinikum der Johann Wolfgang Goethe-Universität, Haus 1 Prof. Dr. med. Stefan Zeuzem Theodor-Stern-Kai 7 60590 Frankfurt am Main Germany Dekanat des Fachbereichs Medizin Klinikum der Johann Wolfgang Goethe-Universität, Haus 1 Prof. Dr. med. Stefan Zeuzem Theodor-Stern-Kai 7 60590 Frankfurt am Main Germany Dekanat des Fachbereichs Medizin der Johann Wolfgang Goethe-Universität.FundingElse Kröner-Fresenius-Stiftung (EKFS), Bad Homburg, Germany.DisclosureO. Waidmann: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, AstraZeneca, BMS, Eisai, MSD, Bayer; Financial Interests, Institutional, Principal Investigator: MSD. C. Koch: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, BMS, MSD, Servier, Ipsen, Merck KG. T.O. Götze: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, AstraZeneca; Financial Interests, Speaker, Consultant, Advisor: Bayer, BMS, Daiichi Sankyo, Foundation Medicine, Eli Lilly, MCI, MSD Sharp & Dohme, Novartis, Roche, Sanofi, Servier, Deciphera; Financial Interests, Steering Committee Member: Boehringer Ingelheim. M. Schultheiss: Financial Interests, Speaker, Consultant, Advisor: Falk Foundation e.V, W. L. Gore & Associates, Entley InnoMed GmbH, Roche Pharma AG. C. Steup: Financial Interests, Funding: Servier. J. Trojan: Financial Interests, Speaker, Consultant, Advisor: Amgen, AstraZeneca, Bristol Myers Squibb, Eisai, Ipsen, Merck Serono, Merck Sharp & Dohme, Lilly Imclone, OnkowissenTV, Roche, Servier. S. Zeuzem: Financial Interests, Speaker, Consultant, Advisor: AbbVie, BioMarin, Boehringer Ingelheim, Gilead, GSK, Ipsen, Madrigal, MSD, Novo Nordisk, SoBi. F. Finkelmeier: Financial Interests, Speaker, Consultant, Advisor: Ipsen, AbbVie, AstraZeneca, MSD, Fresenius. All other authors have declared no conflicts of interest.