Posttreatment after Lenvatinib in Patients with Advanced Hepatocellular Carcinoma.

Hepatocellular carcinoma Lenvatinib Posttreatment

Journal

Liver cancer
ISSN: 2235-1795
Titre abrégé: Liver Cancer
Pays: Switzerland
ID NLM: 101597993

Informations de publication

Date de publication:
Sep 2021
Historique:
received: 14 09 2020
accepted: 27 02 2021
entrez: 1 11 2021
pubmed: 2 11 2021
medline: 2 11 2021
Statut: epublish

Résumé

There is no standard posttreatment for patients with advanced hepatocellular carcinoma (HCC) in whom lenvatinib therapy has failed. This study aimed to investigate rates of migration to posttreatment after lenvatinib and to explore candidates for second-line agents in the patients with failed lenvatinib therapy. We retrospectively collected data on patients with advanced HCC who received lenvatinib as the first-line agent in 7 institutions. Overall survival and progression-free survival (PFS) of 178 patients who received lenvatinib as the first-line agent were 13.3 months (95% confidence interval [CI], 11.5-15.2) and 6.7 months (95% CI, 5.6-7.8), respectively. Sixty-nine of 151 patients (45.7%) who discontinued lenvatinib moved on to posttreatment. The migration rates from lenvatinib to the second-line agent and from the second-line agent to the third-line agent were 41.7 and 44.4%, respectively. Based on multivariate analysis, response to lenvatinib (complete or partial response according to modified RECIST) and discontinuation of lenvatinib due to radiological progression, as well as male were associated with a significantly higher probability of migration to posttreatment after lenvatinib. On the other hand, alpha-fetoprotein levels of 400 ng/mL or higher was correlated with a significantly lower probability of migration to posttreatment after lenvatinib. Of 63 patients who received second-line systemic therapy, 53 (84.2%) were administered sorafenib. PFS, objective response rate (ORR), and disease control rate (DCR) for sorafenib treatment were 1.8 months (95% CI, 0.6-3.0), 1.8%, and 20.8%, respectively. According to the Cox regression hazard model, Child-Pugh class B significantly contributed to shorter PFS. PFS, ORR, and DCR of 22 patients who received regorafenib after lenvatinib in any lines were 3.2 months (range, 1.5-4.9 months), 13.6%, and 36.3%, respectively. Similarly, PFS, ORR, and DCR of 17 patients who received regorafenib after lenvatinib in the third-line (after sorafenib) were 3.8 months (range, 1.1-6.5 months), 17.6%, and 41.2%, respectively. Sorafenib may not be a candidate for use as a posttreatment agent after lenvatinib, according to the results of the present study. Regorafenib has the potential to become an appropriate posttreatment agent after lenvatinib.

Sections du résumé

BACKGROUND BACKGROUND
There is no standard posttreatment for patients with advanced hepatocellular carcinoma (HCC) in whom lenvatinib therapy has failed. This study aimed to investigate rates of migration to posttreatment after lenvatinib and to explore candidates for second-line agents in the patients with failed lenvatinib therapy.
METHODS METHODS
We retrospectively collected data on patients with advanced HCC who received lenvatinib as the first-line agent in 7 institutions.
RESULTS RESULTS
Overall survival and progression-free survival (PFS) of 178 patients who received lenvatinib as the first-line agent were 13.3 months (95% confidence interval [CI], 11.5-15.2) and 6.7 months (95% CI, 5.6-7.8), respectively. Sixty-nine of 151 patients (45.7%) who discontinued lenvatinib moved on to posttreatment. The migration rates from lenvatinib to the second-line agent and from the second-line agent to the third-line agent were 41.7 and 44.4%, respectively. Based on multivariate analysis, response to lenvatinib (complete or partial response according to modified RECIST) and discontinuation of lenvatinib due to radiological progression, as well as male were associated with a significantly higher probability of migration to posttreatment after lenvatinib. On the other hand, alpha-fetoprotein levels of 400 ng/mL or higher was correlated with a significantly lower probability of migration to posttreatment after lenvatinib. Of 63 patients who received second-line systemic therapy, 53 (84.2%) were administered sorafenib. PFS, objective response rate (ORR), and disease control rate (DCR) for sorafenib treatment were 1.8 months (95% CI, 0.6-3.0), 1.8%, and 20.8%, respectively. According to the Cox regression hazard model, Child-Pugh class B significantly contributed to shorter PFS. PFS, ORR, and DCR of 22 patients who received regorafenib after lenvatinib in any lines were 3.2 months (range, 1.5-4.9 months), 13.6%, and 36.3%, respectively. Similarly, PFS, ORR, and DCR of 17 patients who received regorafenib after lenvatinib in the third-line (after sorafenib) were 3.8 months (range, 1.1-6.5 months), 17.6%, and 41.2%, respectively.
CONCLUSION CONCLUSIONS
Sorafenib may not be a candidate for use as a posttreatment agent after lenvatinib, according to the results of the present study. Regorafenib has the potential to become an appropriate posttreatment agent after lenvatinib.

Identifiants

pubmed: 34721509
doi: 10.1159/000515552
pii: lic-0010-0473
pmc: PMC8527907
doi:

Types de publication

Journal Article

Langues

eng

Pagination

473-484

Informations de copyright

Copyright © 2021 by S. Karger AG, Basel.

Déclaration de conflit d'intérêts

Sadahisa Ogasawara received grant support from Eisai, Bayer, and Eli Lilly, advisory fees from Eisai, Bayer, MSD, AstraZeneca, and Eli Lilly, and honoraria from Eisai, Bayer, MSD, AstraZeneca, and Eli Lilly. Yoshihiko Ooka received honoraria from Eisai. Naoya Kato received grant support from Eisai, Bayer, Takeda, and Eli Lilly, advisory fees from Eisai, Bayer, and Eli Lilly, and honoraria from Eisai, Bayer, and Eli Lilly. The other authors have no conflicts of interest to declare.

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Auteurs

Keisuke Koroki (K)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Naoya Kanogawa (N)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Susumu Maruta (S)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.

Sadahisa Ogasawara (S)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Translational Research and Development Center, Chiba University Hospital, Chiba, Japan.

Yotaro Iino (Y)

Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan.

Masamichi Obu (M)

Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan.

Tomomi Okubo (T)

Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan.

Norio Itokawa (N)

Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

Takahiro Maeda (T)

Translational Research and Development Center, Chiba University Hospital, Chiba, Japan.

Masanori Inoue (M)

Translational Research and Development Center, Chiba University Hospital, Chiba, Japan.

Yuki Haga (Y)

Department of Gastroenterology, National Hospital Organization Chiba Medical Center, Chiba, Japan.

Atsuyoshi Seki (A)

Department of Gastroenterology, Funabashi Municipal Medical Center, Funabashi, Japan.

Shinichiro Okabe (S)

Department of Gastroenterology, Matsudo City General Hospital, Matsudo, Japan.

Yoshihiro Koma (Y)

Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan.

Ryosaku Azemoto (R)

Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan.

Masanori Atsukawa (M)

Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

Ei Itobayashi (E)

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

Kenji Ito (K)

Department of Gastroenterology, National Hospital Organization Chiba Medical Center, Chiba, Japan.

Nobuyuki Sugiura (N)

Department of Gastroenterology, National Hospital Organization Chiba Medical Center, Chiba, Japan.

Hideaki Mizumoto (H)

Department of Gastroenterology, Funabashi Municipal Medical Center, Funabashi, Japan.

Hidemi Unozawa (H)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Terunao Iwanaga (T)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Takafumi Sakuma (T)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Naoto Fujita (N)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Hiroaki Kanzaki (H)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Kazufumi Kobayashi (K)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.

Soichiro Kiyono (S)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Masato Nakamura (M)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Tomoko Saito (T)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Takayuki Kondo (T)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Eiichiro Suzuki (E)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Yoshihiko Ooka (Y)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Shingo Nakamoto (S)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Akinobu Tawada (A)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Tetsuhiro Chiba (T)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Makoto Arai (M)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Tatsuo Kanda (T)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Hitoshi Maruyama (H)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

Jun Kato (J)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Naoya Kato (N)

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Classifications MeSH