Makoto Chuma1, Haruki Uojima2, Atsushi Hiraoka3, Satoshi Kobayashi4, Hidenori Toyoda5, Toshifumi Tada6, Hisashi Hidaka2, Shogo Iwabuchi7, Kazushi Numata1, Ei Itobayashi8, Norio Itokawa9, Kazuya Kariyama10, Hideko Ohama11, Nobuhiro Hattori12, Shunji Hirose13, Hiroshi Shibata14, Joji Tani15, Michitaka Imai16, Kazuto Tajiri17, Satoshi Moriya1, Naohisa Wada2, Shuitirou Iwasaki2, Taito Fukushima4, Makoto Ueno4, Satoshi Yasuda5, Masanori Atsukawa9, Kazuhiro Nouso10, Shinya Fukunishi11, Tsunamasa Watanabe12, Toru Ishikawa16, Shinichiro Nakamura6, Manabu Morimoto4, Tatehiro Kagawa13, Michiie Sakamoto18, Takashi Kumada5,19, Shin Maeda20. 1. Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan. 2. Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan. 3. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan. 4. Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan. 5. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan. 6. Department of Gastroenterology, Himeji Red Cross Hospital, Himeji, Hyogo, Japan. 7. Department of Gastroenterology, Shonan Fujisawa General Hospital, Fujisawa, Japan. 8. Department of Gastroenterology, Asahi General Hospital, Asahi, Japan. 9. Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan. 10. Department of Gastroenterology, Okayama City Hospital, Okayama, Japan. 11. Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Japan. 12. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan. 13. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan. 14. Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan. 15. Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kagawa, Japan. 16. Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan. 17. Department of Gastroenterology, Toyama University Hospital, Toyama, Japan. 18. Department of Pathology, Keio University School of Medicine, Tokyo, Japan. 19. Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan. 20. Department of Gastroenterology, Yokohama City University Hospital, Yokohama, Japan.
Abstract
PURPOSE: To assess the safety, efficacy and prognostic impact of clinical factors associated with lenvatinib treatment in highly advanced hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein trunk (VP4) or tumor with more than 50% liver occupation (tm50%LO). METHOD: Sixty-one highly advanced HCC patients (41 patients with tm50%LO and 20 patients with VP4) who were treated with lenvatinib at multicenter were enrolled and retrospectively analyzed for treatment outcomes according to their clinical status, including tumor morphology. RESULTS: The most frequent ≥ grade 3 adverse event in tm50%LO HCC was elevated aspartate aminotransferase (17.1%). Objective response rates were 37.5% and 0% in tm50%LO HCC patients with Child-Pugh grade (CP)-A and CP-B, respectively and 26.7% and 0% in VP4 HCC patients with CP-A and CP-B, respectively. Estimated median progression free survival (PFS) and overall survival (OS) were 132 days and 229 days, and 101 days and 201 days in patients with tm50%LO and VP4, respectively. In multivariate analysis, modified albumin-bilirubin (mALBI) grade (hazard ratio (HR), 0.372; 95%CI, 0.157-0.887; P=0.0241) and tumor morphology (HR, 0.322; 95%CI, 0.116-0.889; P=0.0287) were independently associated with PFS in patients with tm50%LO HCC. In VP4 HCC, median PFS was worse in CP-B (57 days) than in CP-A patients (137 days, P=0.0462). CONCLUSION: Lenvatinib treatment offers a benefit in highly advanced HCC (tm50%LO or VP4) patients with good liver function or nodular type tumor. The various characteristics identified in this study might be useful as indicators of lenvatinib treatment in highly advanced HCC with tm50%LO or VP4, which are considered very refractory cancers. This article is protected by copyright. All rights reserved.
PURPOSE: To assess the safety, efficacy and prognostic impact of clinical factors associated with lenvatinib treatment in highly advanced hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein trunk (VP4) or tumor with more than 50% liver occupation (tm50%LO). METHOD: Sixty-one highly advanced HCC patients (41 patients with tm50%LO and 20 patients with VP4) who were treated with lenvatinib at multicenter were enrolled and retrospectively analyzed for treatment outcomes according to their clinical status, including tumor morphology. RESULTS: The most frequent ≥ grade 3 adverse event in tm50%LO HCC was elevated aspartate aminotransferase (17.1%). Objective response rates were 37.5% and 0% in tm50%LO HCC patients with Child-Pugh grade (CP)-A and CP-B, respectively and 26.7% and 0% in VP4 HCC patients with CP-A and CP-B, respectively. Estimated median progression free survival (PFS) and overall survival (OS) were 132 days and 229 days, and 101 days and 201 days in patients with tm50%LO and VP4, respectively. In multivariate analysis, modified albumin-bilirubin (mALBI) grade (hazard ratio (HR), 0.372; 95%CI, 0.157-0.887; P=0.0241) and tumor morphology (HR, 0.322; 95%CI, 0.116-0.889; P=0.0287) were independently associated with PFS in patients with tm50%LO HCC. In VP4 HCC, median PFS was worse in CP-B (57 days) than in CP-Apatients (137 days, P=0.0462). CONCLUSION:Lenvatinib treatment offers a benefit in highly advanced HCC (tm50%LO or VP4) patients with good liver function or nodular type tumor. The various characteristics identified in this study might be useful as indicators of lenvatinib treatment in highly advanced HCC with tm50%LO or VP4, which are considered very refractory cancers. This article is protected by copyright. All rights reserved.