Important Clinical Factors in Sequential Therapy Including Lenvatinib against Unresectable Hepatocellular Carcinoma.

Aged Bilirubin / blood Carcinoma, Hepatocellular / drug therapy Female Humans Liver Neoplasms / drug therapy Male Phenylurea Compounds / therapeutic use Prognosis Protein Kinase Inhibitors / therapeutic use Quinolines / therapeutic use Serum Albumin / analysis
Albumin-bilirubin grade, modified Hepatocellular carcinoma Lenvatinib Regorafenib Sequential therapy Sorafenib

Journal

Oncology
ISSN: 1423-0232
Titre abrégé: Oncology
Pays: Switzerland
ID NLM: 0135054

Informations de publication

Date de publication:
2019
Historique:
received: 14 05 2019
accepted: 29 05 2019
pubmed: 16 7 2019
medline: 15 11 2019
entrez: 16 7 2019
Statut: ppublish

Résumé

We evaluated clinical factors related to improved prognosis of unresectable hepatocellular carcinoma patients (u-HCC), who were treated with tyrosine kinase inhibitor (TKI) sequential therapy, including lenvatinib (LEN). We enrolled 84 u-HCC cases treated with TKIs including LEN from March 2018 to January 2019 (median age 71 years, 63 males, Child-Pugh score (CPS) 5/6/7 = 62/21/1, tumor-node-metastasis stage of Liver Cancer Study Group of Japan 6th (TNM-LCSGJ) II/III/IVa/IVb = 12/30/5/37, Barcelona Clinic Liver Cancer stage B/C = 33:51). Clinical findings at introduction of the initial TKI were retrospectively evaluated. The median albumin-bilirubin (ALBI) score at introduction of the initial TKI (sorafenib [SOR]/LEN = 80/4) was -2.56, and the past number of transarterial catheter chemoembolization was 3 (IQR: 2-5) (second-line: regorafenib [REG]/LEN/SOR = 31/49/4, third-line: LEN/REG = 31:1). The total period of administration with TKIs showed a good relationship with overall survival (OS) (r = 0.946, 95% confidence interval [CI]: 0.918-0.965, p < 0.001). The prognosis of the entire cohort was good (estimated median survival time: 46.4 months, 1-/2-/3-year OS rate [OSR] = 87.7/63.0/57.2%). A modified-ALBI grade (mALBI) of 2b (ALBI score >-2.27) was the only significant factor at the start of the initial TKI for poor prognosis (hazard ratio 2.319, 95% CI: 1.064-5.052, p = 0.034), while CPS (≥6) was not. Although there was no significant difference in TNM-LCSGJ (p = 0.213), the prognosis of patients with mALBI 1/2a (n = 66) showed better prognosis as compared to those with mALBI 2b (n = 18) (1-year/2-year/3-year OSR = 89.1/69.8/66% vs. 82.4/47.1/23.5%, p = 0.029). Good hepatic function (mALBI 1/2a) at introduction of the initial TKI is a requirement for improved prognosis of u-HCC undergoing TKI sequential therapy.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
We evaluated clinical factors related to improved prognosis of unresectable hepatocellular carcinoma patients (u-HCC), who were treated with tyrosine kinase inhibitor (TKI) sequential therapy, including lenvatinib (LEN).
MATERIALS/METHODS METHODS
We enrolled 84 u-HCC cases treated with TKIs including LEN from March 2018 to January 2019 (median age 71 years, 63 males, Child-Pugh score (CPS) 5/6/7 = 62/21/1, tumor-node-metastasis stage of Liver Cancer Study Group of Japan 6th (TNM-LCSGJ) II/III/IVa/IVb = 12/30/5/37, Barcelona Clinic Liver Cancer stage B/C = 33:51). Clinical findings at introduction of the initial TKI were retrospectively evaluated.
RESULTS RESULTS
The median albumin-bilirubin (ALBI) score at introduction of the initial TKI (sorafenib [SOR]/LEN = 80/4) was -2.56, and the past number of transarterial catheter chemoembolization was 3 (IQR: 2-5) (second-line: regorafenib [REG]/LEN/SOR = 31/49/4, third-line: LEN/REG = 31:1). The total period of administration with TKIs showed a good relationship with overall survival (OS) (r = 0.946, 95% confidence interval [CI]: 0.918-0.965, p < 0.001). The prognosis of the entire cohort was good (estimated median survival time: 46.4 months, 1-/2-/3-year OS rate [OSR] = 87.7/63.0/57.2%). A modified-ALBI grade (mALBI) of 2b (ALBI score >-2.27) was the only significant factor at the start of the initial TKI for poor prognosis (hazard ratio 2.319, 95% CI: 1.064-5.052, p = 0.034), while CPS (≥6) was not. Although there was no significant difference in TNM-LCSGJ (p = 0.213), the prognosis of patients with mALBI 1/2a (n = 66) showed better prognosis as compared to those with mALBI 2b (n = 18) (1-year/2-year/3-year OSR = 89.1/69.8/66% vs. 82.4/47.1/23.5%, p = 0.029).
CONCLUSION CONCLUSIONS
Good hepatic function (mALBI 1/2a) at introduction of the initial TKI is a requirement for improved prognosis of u-HCC undergoing TKI sequential therapy.

Identifiants

DOI: 10.1159/000501281 PMID: 31307035
pubmed: 31307035
pii: 000501281
doi: 10.1159/000501281
doi:

Substances chimiques

Phenylurea Compounds 0
Protein Kinase Inhibitors 0
Quinolines 0
Serum Albumin 0
lenvatinib EE083865G2
Bilirubin RFM9X3LJ49

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

277-285

Informations de copyright

© 2019 S. Karger AG, Basel.

Auteurs

Atsushi Hiraoka (A)

Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan, hirage@m.ehime-u.ac.jp.

Takashi Kumada (T)

Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan.

Masanori Atsukawa (M)

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

Masashi Hirooka (M)

Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan.

Kunihiko Tsuji (K)

Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.

Toru Ishikawa (T)

Department of Gastroenterology, Saiseikai Niigata Daini Hospital, Niigata, Japan.

Koichi Takaguchi (K)

Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.

Kazuya Kariyama (K)

Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.

Ei Itobayashi (E)

Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.

Kazuto Tajiri (K)

Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.

Noritomo Shimada (N)

Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan.

Hiroshi Shibata (H)

Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan.

Hironori Ochi (H)

Hepatobiliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan.

Toshifumi Tada (T)

Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan.

Hidenori Toyoda (H)

Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan.

Kazuhiro Nouso (K)

Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.

Akemi Tsutsui (A)

Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.

Takuya Nagano (T)

Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.

Norio Itokawa (N)

Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.

Korenobu Hayama (K)

Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.

Michitaka Imai (M)

Department of Gastroenterology, Saiseikai Niigata Daini Hospital, Niigata, Japan.

Kouji Joko (K)

Hepatobiliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan.

Hironori Tanaka (H)

Department of Gastroenterology, Takarazuka City Hospital, Takarazuka, Japan.

Tsutomu Tamai (T)

Department of Gastroenterology, Kagoshima City Hospital, Kagoshima, Japan.

Yohei Koizumi (Y)

Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan.

Yoichi Hiasa (Y)

Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan.

Kojiro Michitaka (K)

Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.

Masatoshi Kudo (M)

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.

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Classifications MeSH

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