Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma : A Randomized, Multicenter, Open-Label Phase 3 Trial

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Geissler , E K , Schnitzbauer , A A , Zuelke , C , Lamby , P E , Proneth , A , Duvoux , C , Burra , P , Jauch , K-W , Rentsch , M , Ganten , T M , Schmidt , J , Settmacher , U , Heise , M , Rossi , G , Cillo , U , Kneteman , N , Adam , R , van Hoek , B , Bachellier , P , Wolf , P , Rostaing , L , Bechstein , W O , Rizell , M , Powell , J , Hidalgo , E , Gugenheim , J , Wolters , H , Brockmann , J , Roy , A , Mutzbauer , I , Schlitt , A , Beckebaum , S , Graeb , C , Nadalin , S , Valente , U , Sanchez Turrion , V , Jamieson , N , Scholz , T , Colledan , M , Faendrich , F , Becker , T , Soderdahl , G , Chazouilleres , O , Mäkisalo , H , Pageaux , G-P , Steininger , R , Soliman , T , de Jong , K P , Pirenne , J , Margreiter , R , Pratschke , J , Pinna , A D , Hauss , J , Schreiber , S , Strasser , S , Klempnauer , J , Troisi , R I , Bhoori , S , Lerut , J , Bilbao , I , Klein , C G , Koenigsrainer , A , Mirza , D F , Otto , G , Mazzaferro , V , Neuhaus , P & Schlitt , H J 2016 , ' Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma : A Randomized, Multicenter, Open-Label Phase 3 Trial ' , Transplantation , vol. 100 , no. 1 , pp. 116-125 . https://doi.org/10.1097/TP.0000000000000965

Title: Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma : A Randomized, Multicenter, Open-Label Phase 3 Trial
Author: Geissler, Edward K.; Schnitzbauer, Andreas A.; Zuelke, Carl; Lamby, Philipp E.; Proneth, Andrea; Duvoux, Christophe; Burra, Patrizia; Jauch, Karl-Walter; Rentsch, Markus; Ganten, Tom M.; Schmidt, Jan; Settmacher, Utz; Heise, Michael; Rossi, Giorgio; Cillo, Umberto; Kneteman, Norman; Adam, Rene; van Hoek, Bart; Bachellier, Philippe; Wolf, Philippe; Rostaing, Lionel; Bechstein, Wolf O.; Rizell, Magnus; Powell, James; Hidalgo, Ernest; Gugenheim, Jean; Wolters, Heiner; Brockmann, Jens; Roy, Andre; Mutzbauer, Ingrid; Schlitt, Angela; Beckebaum, Susanne; Graeb, Christian; Nadalin, Silvio; Valente, Umberto; Sanchez Turrion, Victor; Jamieson, Neville; Scholz, Tim; Colledan, Michele; Faendrich, Fred; Becker, Thomas; Soderdahl, Gunnar; Chazouilleres, Olivier; Mäkisalo, Heikki; Pageaux, Georges-Philippe; Steininger, Rudolf; Soliman, Thomas; de Jong, Koert P.; Pirenne, Jacques; Margreiter, Raimund; Pratschke, Johann; Pinna, Antonio D.; Hauss, Johann; Schreiber, Stefan; Strasser, Simone; Klempnauer, Juergen; Troisi, Roberto I.; Bhoori, Sherrie; Lerut, Jan; Bilbao, Itxarone; Klein, Christian G.; Koenigsrainer, Alfred; Mirza, Darius F.; Otto, Gerd; Mazzaferro, Vincenzo; Neuhaus, Peter; Schlitt, Hans J.
Contributor: University of Helsinki, IV kirurgian klinikka
Date: 2016-01
Language: eng
Number of pages: 10
Belongs to series: Transplantation
ISSN: 0041-1337
URI: http://hdl.handle.net/10138/163149
Abstract: Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age 60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.
Subject: RENAL-CELL CARCINOMA
RAPAMYCIN INHIBITORS
IMMUNOSUPPRESSION
RECURRENCE
SURVIVAL
TARGET
CANCER
METAANALYSIS
PROGRESSION
EVEROLIMUS
3126 Surgery, anesthesiology, intensive care, radiology
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