Keisuke Koroki1, Naoya Kanogawa1, Susumu Maruta2,1, Sadahisa Ogasawara1,3, Yotaro Iino4, Masamichi Obu4, Tomomi Okubo5, Norio Itokawa6,5, Takahiro Maeda3, Masanori Inoue3, Yuki Haga7, Atsuyoshi Seki8, Shinichiro Okabe9, Yoshihiro Koma4, Ryosaku Azemoto4, Masanori Atsukawa6,5, Ei Itobayashi2, Kenji Ito7, Nobuyuki Sugiura7, Hideaki Mizumoto8, Hidemi Unozawa1, T. Iwanaga1, Takafumi Sakuma1, Naoto Fujita1, Hiroaki Kanzaki1, Kazufumi Kobayashi2,1, Soichiro Kiyono1, Masato Nakamura1, Tetsuhiro Chiba1, Takayuki Kondo1, Eiichiro Suzuki1, Yoshihiko Ooka1, Shingo Nakamoto1, Akinobu Tawada1,10, Makoto Arai1,10, Tatsuo Kanda1,11, Hitoshi Maruyama1,12, Jun Kato1, Naoya Kato1
1Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
2Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
3Translational Research and Development Center, Chiba University Hospital, Chiba, Japan
4Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu, Japan
5Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
6Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
7Department of Gastroenterology, National Hospital Organization Chiba Medical Center, Chiba, Japan
8Department of Gastroenterology, Funabashi Municipal Medical Center, Funabashi, Japan
9Department of Gastroenterology, Matsudo City General Hospital, Matsudo, Japan
10Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
11Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
12Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
Tóm tắt
<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> We retrospectively collected data on patients with advanced HCC who received lenvatinib as the first-line agent in 7 institutions. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.
