The Real-World Data in Japanese Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib from a Nationwide Multicenter Study

Kaoru Tsuchiya; Masayuki Kurosaki; Azusa Sakamoto; Hiroyuki Marusawa; Yuji Kojima; Chitomi Hasebe; Hirotaka Arai; Kouji Joko; Masahiko Kondo; Keiji Tsuji; Tetsuro Sohda; Hiroyuki Kimura; Chikara Ogawa; Yasushi Uchida; Shuichi Wada; Haruhiko Kobashi; Koichiro Furuta; Masaya Shigeno; Atsunori Kusakabe; Takehiro Akahane; Ryoichi Narita; Hideo Yoshida; Akeri Mitsuda; Yasushi Ide; Tomomichi Matsushita; Namiki Izumi; On Behalf Of Japanese Red Cross Liver Study Group

doi:10.3390/cancers13112608

The Real-World Data in Japanese Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib from a Nationwide Multicenter Study

Cancers (Basel). 2021 May 26;13(11):2608. doi: 10.3390/cancers13112608.

Authors

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, On Behalf Of Japanese Red Cross Liver Study Group

Affiliations

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.

Keywords: AFP; ALBI grade; bone metastasis; hepatocellular carcinoma; lenvatinib.

Grants and funding

JP19fk0210025h0003/Japan Agency for Medical Research and Development