Posttreatment after Lenvatinib in Patients with Advanced Hepatocellular Carcinoma

Keisuke Koroki; Naoya Kanogawa; Susumu Maruta; Sadahisa Ogasawara; Yotaro Iino; Masamichi Obu; Tomomi Okubo; Norio Itokawa; Takahiro Maeda; Masanori Inoue; Yuki Haga; Atsuyoshi Seki; Shinichiro Okabe; Yoshihiro Koma; Ryosaku Azemoto; Masanori Atsukawa; Ei Itobayashi; Kenji Ito; Nobuyuki Sugiura; Hideaki Mizumoto; Hidemi Unozawa; Terunao Iwanaga; Takafumi Sakuma; Naoto Fujita; Hiroaki Kanzaki; Kazufumi Kobayashi; Soichiro Kiyono; Masato Nakamura; Tomoko Saito; Takayuki Kondo; Eiichiro Suzuki; Yoshihiko Ooka; Shingo Nakamoto; Akinobu Tawada; Tetsuhiro Chiba; Makoto Arai; Tatsuo Kanda; Hitoshi Maruyama; Jun Kato; Naoya Kato

doi:10.1159/000515552

Posttreatment after Lenvatinib in Patients with Advanced Hepatocellular Carcinoma

Liver Cancer. 2021 Apr 20;10(5):473-484. doi: 10.1159/000515552. eCollection 2021 Sep.

Authors

Keisuke Koroki¹, Naoya Kanogawa¹, Susumu Maruta^{1

2}, Sadahisa Ogasawara^{1

3}, Yotaro Iino⁴, Masamichi Obu⁴, Tomomi Okubo⁵, Norio Itokawa^{5

6}, Takahiro Maeda³, Masanori Inoue³, Yuki Haga⁷, Atsuyoshi Seki⁸, Shinichiro Okabe⁹, Yoshihiro Koma⁴, Ryosaku Azemoto⁴, Masanori Atsukawa^{5

6}, Ei Itobayashi², Kenji Ito⁷, Nobuyuki Sugiura⁷, Hideaki Mizumoto⁸, Hidemi Unozawa¹, Terunao Iwanaga¹, Takafumi Sakuma¹, Naoto Fujita¹, Hiroaki Kanzaki¹, Kazufumi Kobayashi^{1

2}, Soichiro Kiyono¹, Masato Nakamura¹, Tomoko Saito¹, Takayuki Kondo¹, Eiichiro Suzuki¹, Yoshihiko Ooka¹, Shingo Nakamoto¹, Akinobu Tawada^{1

10}, Tetsuhiro Chiba¹, Makoto Arai^{1

10}, Tatsuo Kanda^{1

11}, Hitoshi Maruyama^{1

12}, Jun Kato¹, Naoya Kato¹

Affiliations

¹ Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
² Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.
³ Translational Research and Development Center, Chiba University Hospital, Chiba, Japan.
⁴ Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan.
⁵ Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan.
⁶ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
⁷ Department of Gastroenterology, National Hospital Organization Chiba Medical Center, Chiba, Japan.
⁸ Department of Gastroenterology, Funabashi Municipal Medical Center, Funabashi, Japan.
⁹ Department of Gastroenterology, Matsudo City General Hospital, Matsudo, Japan.
¹⁰ Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
¹¹ Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
¹² Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.

Abstract

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: We retrospectively collected data on patients with advanced HCC who received lenvatinib as the first-line agent in 7 institutions.

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: 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.

Keywords: Hepatocellular carcinoma; Lenvatinib; Posttreatment.