Kaoru Tsuchiya1, Masayuki Kurosaki1, Azusa Sakamoto2, Hiroyuki Marusawa2, Yuji Kojima3, Chitomi Hasebe4, Hirotaka Arai5, Kouji Joko6, Masahiko Kondo7, Keiji Tsuji8, Tetsuro Sohda9, Hiroyuki Kimura10, Chikara Ogawa11, Yasushi Uchida12, Shuichi Wada13, Haruhiko Kobashi14, Koichiro Furuta15, Masaya Shigeno16, Atsunori Kusakabe17, Takehiro Akahane18, Ryoichi Narita19, Hideo Yoshida20, Akeri Mitsuda21, Yasushi Ide22, Tomomichi Matsushita23, Namiki Izumi1. 1. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan. 2. Department of Gastroenterology and Hepatology, Japanese Red Cross Osaka Hospital, Osaka 543-855, Japan. 3. Department of Gastroenterology and Hepatology, Japanese Red Cross Ise Hospital, Ise 516-8512, Japan. 4. Department of Gastroenterology and Hepatology, Japanese Red Cross Asahikawa Hospital, Asahikawa 070-8530, Japan. 5. Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital, Maebashi 371-0811, Japan. 6. Department of Gastroenterology and Hepatology, Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan. 7. Department of Gastroenterology and Hepatology, Japanese Red Cross Otsu Hospital, Otsu 520-0046, Japan. 8. Department of Gastroenterology and Hepatology Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima 730-0052, Japan. 9. Department of Hepatology, Japanese Red Cross Fukuoka Hospital, Fukuoka 815-8555, Japan. 10. Department of Gastroenterology and Hepatology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto 605-0981, Japan. 11. Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu 760-0017, Japan. 12. Department of Gastroenterology and Hepatology, Matsue Red Cross Hospital, Matsue 690-0886, Japan. 13. Department of Gastroenterology and Hepatology, Japanese Red Cross Nagano Hospital, Nagano 380-0928, Japan. 14. Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama 770-8607, Japan. 15. Department of Gastroenterology and Hepatology, Japanese Red Cross Masuda Hospital, Masuda 698-8501, Japan. 16. Department of Gastroenterology and Hepatology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki 852-8511, Japan. 17. Department of Gastroenterology and Hepatology, Japanese Red Cross Nagoya Daini Hospital, Nagoya 466-8650, Japan. 18. Department of Gastroenterology and Hepatology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki 986-8522, Japan. 19. Department of Hepatology, Japanese Red Cross Oita Hospital, Oita 870-0033, Japan. 20. Department of Gastroenterology and Hepatology, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan. 21. Department of Gastroenterology and Hepatology, Japanese Red Cross Tottori Hospital, Tottori 680-8517, Japan. 22. Department of Gastroenterology and Hepatology, Japanese Red Cross Karatsu Hospital, Karatsu 847-8588, Japan. 23. Department of Gastroenterology and Hepatology, Japanese Red Cross Gifu Hospital, Gifu 502-8511, Japan.
Abstract
BACKGROUND: Lenvatinib (LEN) has been approved for patients with unresectable hepatocellular carcinoma (u-HCC) since March 2018 in Japan. We performed a retrospective nationwide multicenter study to clarify the clinical characteristics of LEN in real-world practice. METHODS: A total of 343 u-HCC patients who received LEN from March 2018 to May 2020 at 23 sites in Japan were registered. RESULTS: During the median observation period of 10.5 months, 143 patients died. In Child-Pugh A (n = 276) and Child-Pugh B (n = 67) patients, the median overall survival (OS) was 21.0 and 9.0 months. The median progression-free survival (PFS) was 8.8 months in Child-Pugh A patients. The objective response rate (ORR) and disease control rate (DCR) according to modified response evaluation criteria in solid tumors (RECIST criteria) were 42.1% and 82.1%. The independent pretreatment factors associated with mortality in all patients were AFP ≥ 400 ng/mL (hazard ratio (HR) 2.00, 95% confidential interval (95% CI) 1.08-2.09, p < 0.0001), modified albumin-bilirubin (ALBI) grade 2b or 3 (HR 1.56, 95% CI 1.09-2.17, p = 0.012), major vascular invasion (HR 1.91, 95% CI 1.26-2.89, p = 0.0022), PS > 0 (HR 1.50, 95% CI 1.09-2.08, p = 0.014), and MTT (molecular targeted therapy) experience (HR 2.22, 95% CI 1.56-3.13, p = 0.00038). In the MTT naïve patients with ALBI grade 1 or modified ALBI 2a and BCLC stage B (n = 68), median OS and PFS were 25.3 and 12.3 months. Liver-related adverse events during LEN were the only significant adverse event associated with OS (HR 2.74, 95% CI 1.93-3.88, p < 0.0001). Among the Child-Pugh A patients with extrahepatic metastasis and no major vascular invasion, median PFS in the patients with bone metastasis was significantly shorter than those with lung or adrenal grand metastasis (6.3 vs. 12.5 months, p = 0.0025). CONCLUSION: LEN showed a high response rate in real-world practice. Pretreatment factors, including ALBI score, AFP, and major vascular invasion are important in making a treatment strategy for patients with u-HCC. The patients with bone metastasis would be candidates for new therapeutic approaches.
BACKGROUND:Lenvatinib (LEN) has been approved for patients with unresectable hepatocellular carcinoma (u-HCC) since March 2018 in Japan. We performed a retrospective nationwide multicenter study to clarify the clinical characteristics of LEN in real-world practice. METHODS: A total of 343 u-HCC patients who received LEN from March 2018 to May 2020 at 23 sites in Japan were registered. RESULTS: During the median observation period of 10.5 months, 143 patientsdied. In Child-Pugh A (n = 276) and Child-Pugh B (n = 67) patients, the median overall survival (OS) was 21.0 and 9.0 months. The median progression-free survival (PFS) was 8.8 months in Child-Pugh A patients. The objective response rate (ORR) and disease control rate (DCR) according to modified response evaluation criteria in solid tumors (RECIST criteria) were 42.1% and 82.1%. The independent pretreatment factors associated with mortality in all patients were AFP ≥ 400 ng/mL (hazard ratio (HR) 2.00, 95% confidential interval (95% CI) 1.08-2.09, p < 0.0001), modified albumin-bilirubin (ALBI) grade 2b or 3 (HR 1.56, 95% CI 1.09-2.17, p = 0.012), major vascular invasion (HR 1.91, 95% CI 1.26-2.89, p = 0.0022), PS > 0 (HR 1.50, 95% CI 1.09-2.08, p = 0.014), and MTT (molecular targeted therapy) experience (HR 2.22, 95% CI 1.56-3.13, p = 0.00038). In the MTT naïve patients with ALBI grade 1 or modified ALBI 2a and BCLC stage B (n = 68), median OS and PFS were 25.3 and 12.3 months. Liver-related adverse events during LEN were the only significant adverse event associated with OS (HR 2.74, 95% CI 1.93-3.88, p < 0.0001). Among the Child-Pugh A patients with extrahepatic metastasis and no major vascular invasion, median PFS in the patients with bone metastasis was significantly shorter than those with lung or adrenal grand metastasis (6.3 vs. 12.5 months, p = 0.0025). CONCLUSION:LEN showed a high response rate in real-world practice. Pretreatment factors, including ALBI score, AFP, and major vascular invasion are important in making a treatment strategy for patients with u-HCC. The patients with bone metastasis would be candidates for new therapeutic approaches.
Entities:
Keywords:
AFP; ALBI grade; bone metastasis; hepatocellular carcinoma; lenvatinib
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