Analyses of Intermediate-Stage Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization prior to Designing Clinical Trials

• Published in: Liver cancer (Basel ) 2020-09, Vol.9 (5), p.596-612
• Main Authors: Koroki, Keisuke, Ogasawara, Sadahisa, Ooka, Yoshihiko, Kanzaki, Hiroaki, Kanayama, Kengo, Maruta, Susumu, Maeda, Takahiro, Yokoyama, Masayuki, Wakamatsu, Toru, Inoue, Masanori, Kobayashi, Kazufumi, Kiyono, Soichiro, Nakamura, Masato, Kanogawa, Naoya, Saito, Tomoko, Kondo, Takayuki, Suzuki, Eiichiro, Nakamoto, Shingo, Yasui, Shin, Tawada, Akinobu, Chiba, Tetsuhiro, Arai, Makoto, Kanda, Tatsuo, Maruyama, Hitoshi, Kato, Jun, Kuboki, Satoshi, Ohtsuka, Masayuki, Miyazaki, Masaru, Yokosuka, Osamu, Kato, Naoya
• Format: Article
• Language: English
• Subjects: Cancer; Cancer therapies; Care and treatment; Chemoembolization; Clinical trials; durable response rate; hepatocellular carcinoma; Hepatoma; intermediate stage; Liver cancer; Magnetic resonance imaging; Medical prognosis; Metastasis; Original Paper; Patients; Performance evaluation; Pharmaceutical industry; Product development; Response rates; transarterial chemoembolization; Tumors
• ISSN: 2235-1795; 1664-5553
• DOI: 10.1159/000508809

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.