BACKGROUND: There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. METHODS: A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. RESULTS: Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1-18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. CONCLUSION: This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule.
BACKGROUND: There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. METHODS: A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. RESULTS: Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1-18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. CONCLUSION: This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule.
Authors: Abby B Siegel; Emil I Cohen; Allyson Ocean; Deborah Lehrer; Alec Goldenberg; Jennifer J Knox; Helen Chen; Sean Clark-Garvey; Alan Weinberg; John Mandeli; Paul Christos; Madhu Mazumdar; Elizabeta Popa; Robert S Brown; Shahin Rafii; Jonathan D Schwartz Journal: J Clin Oncol Date: 2008-06-20 Impact factor: 44.544
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Authors: Josep M Llovet; Sergio Ricci; Vincenzo Mazzaferro; Philip Hilgard; Edward Gane; Jean-Frédéric Blanc; Andre Cosme de Oliveira; Armando Santoro; Jean-Luc Raoul; Alejandro Forner; Myron Schwartz; Camillo Porta; Stefan Zeuzem; Luigi Bolondi; Tim F Greten; Peter R Galle; Jean-François Seitz; Ivan Borbath; Dieter Häussinger; Tom Giannaris; Minghua Shan; Marius Moscovici; Dimitris Voliotis; Jordi Bruix Journal: N Engl J Med Date: 2008-07-24 Impact factor: 91.245
Authors: R K Kelley; H S Nimeiri; P N Munster; M T Vergo; Y Huang; C-M Li; J Hwang; M F Mulcahy; B M Yeh; P Kuhn; M S Luttgen; J A Grabowsky; L Stucky-Marshall; W M Korn; A H Ko; E K Bergsland; A B Benson; A P Venook Journal: Ann Oncol Date: 2013-03-21 Impact factor: 32.976
Authors: Joanne W Chiu; Sebastien J Hotte; Christian K Kollmannsberger; Daniel J Renouf; David W Cescon; David Hedley; Sue Chow; Jeffrey Moscow; Zhuo Chen; Meghan Perry; Ivan Diaz-Padilla; David Tan; Hal Hirte; Elaine McWhirter; Helen Chen; Lillian L Siu; Philippe L Bedard Journal: Invest New Drugs Date: 2015-12-19 Impact factor: 3.850
Authors: Marina G Tarakanovskaya; Jigjidsuren Chinburen; Purev Batchuluun; Chogsom Munkhzaya; Genden Purevsuren; Dorjiin Dandii; Tsogkhuu Hulan; Dandii Oyungerel; Galyna A Kutsyna; Alan A Reid; Vika Borisova; Allen I Bain; Vichai Jirathitikal; Aldar S Bourinbaiar Journal: J Hepatocell Carcinoma Date: 2017-04-12