Liver Cancer (Apr 2021)

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
https://doi.org/10.1159/000515552

Abstract

Read online

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