BACKGROUND: Intermediate-stage hepatocellular carcinoma (HCC) has a high frequency of recurrence and progression to advanced stage after transarterial chemoembolization (TACE), particularly in patients with high tumor burden. Promising new results from immune checkpoint inhibitors (ICIs) and ICI-based therapies are expected to replace TACE, especially in HCC patients with high tumor burden. AIMS: The present study aimed to evaluate the effectiveness of TACE with a view to design clinical trials comparing TACE and ICIs. METHODS: We retrospectively identified intermediate-stage HCC patients undergoing TACE from our database and subdivided patients into low- and high-burden groups based on three subclassification models using the diameter of the maximum tumor and the number of tumors. Clinical outcomes were compared between low- and high-burden intermediate-stage HCC. RESULTS: Of 1,161 newly diagnosed HCC patients, 316 were diagnosed with intermediate-stage disease and underwent TACE. The median overall survival from high-burden intermediate-stage disease was not significantly different by clinical course, reaching high tumor burden in all subclassification models. The prognosis of high-burden patients after initial TACE was poor compared with low-burden patients for two models (except for the up-to-seven criteria). In all three models, high-burden patients showed a poor durable response rate (DRR) both ≥3 months and ≥6 months and poor prognosis after TACE. Moreover, patients with confirmed durable response ≥3 months and ≥6 months showed better survival outcomes for high-burden intermediate-stage HCC. CONCLUSIONS: Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.
BACKGROUND: Intermediate-stage hepatocellular carcinoma (HCC) has a high frequency of recurrence and progression to advanced stage after transarterial chemoembolization (TACE), particularly in patients with high tumor burden. Promising new results from immune checkpoint inhibitors (ICIs) and ICI-based therapies are expected to replace TACE, especially in HCC patients with high tumor burden. AIMS: The present study aimed to evaluate the effectiveness of TACE with a view to design clinical trials comparing TACE and ICIs. METHODS: We retrospectively identified intermediate-stage HCC patients undergoing TACE from our database and subdivided patients into low- and high-burden groups based on three subclassification models using the diameter of the maximum tumor and the number of tumors. Clinical outcomes were compared between low- and high-burden intermediate-stage HCC. RESULTS: Of 1,161 newly diagnosed HCC patients, 316 were diagnosed with intermediate-stage disease and underwent TACE. The median overall survival from high-burden intermediate-stage disease was not significantly different by clinical course, reaching high tumor burden in all subclassification models. The prognosis of high-burden patients after initial TACE was poor compared with low-burden patients for two models (except for the up-to-seven criteria). In all three models, high-burden patients showed a poor durable response rate (DRR) both ≥3 months and ≥6 months and poor prognosis after TACE. Moreover, patients with confirmed durable response ≥3 months and ≥6 months showed better survival outcomes for high-burden intermediate-stage HCC. CONCLUSIONS: Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.
Authors: Andrew X Zhu; Richard S Finn; Julien Edeline; Stephane Cattan; Sadahisa Ogasawara; Daniel Palmer; Chris Verslype; Vittorina Zagonel; Laetitia Fartoux; Arndt Vogel; Debashis Sarker; Gontran Verset; Stephen L Chan; Jennifer Knox; Bruno Daniele; Andrea L Webber; Scot W Ebbinghaus; Junshui Ma; Abby B Siegel; Ann-Lii Cheng; Masatoshi Kudo Journal: Lancet Oncol Date: 2018-06-03 Impact factor: 41.316
Authors: Robert H I Andtbacka; Howard L Kaufman; Frances Collichio; Thomas Amatruda; Neil Senzer; Jason Chesney; Keith A Delman; Lynn E Spitler; Igor Puzanov; Sanjiv S Agarwala; Mohammed Milhem; Lee Cranmer; Brendan Curti; Karl Lewis; Merrick Ross; Troy Guthrie; Gerald P Linette; Gregory A Daniels; Kevin Harrington; Mark R Middleton; Wilson H Miller; Jonathan S Zager; Yining Ye; Bin Yao; Ai Li; Susan Doleman; Ari VanderWalde; Jennifer Gansert; Robert S Coffin Journal: J Clin Oncol Date: 2015-05-26 Impact factor: 44.544
Authors: David J Pinato; Tadaaki Arizumi; Jeong Won Jang; Elias Allara; Puvan I Suppiah; Carlo Smirne; Paul Tait; Madhava Pai; Glenda Grossi; Young Woon Kim; Mario Pirisi; Masatoshi Kudo; Rohini Sharma Journal: Oncotarget Date: 2016-07-12