Liver Cancer (Feb 2021)

What Can Be Done to Solve the Unmet Clinical Need of Hepatocellular Carcinoma Patients following Lenvatinib Failure?

  • Atsushi Hiraoka,
  • Takashi Kumada,
  • Toshifumi Tada,
  • Kazuya Kariyama,
  • Joji Tani,
  • Shinya Fukunishi,
  • Masanori Atsukawa,
  • Masashi Hirooka,
  • Kunihiko Tsuji,
  • Toru Ishikawa,
  • Koichi Takaguchi,
  • Ei Itobayashi,
  • Kazuto Tajiri,
  • Noritomo Shimada,
  • Hiroshi Shibata,
  • Hironori Ochi,
  • Kazuhito Kawata,
  • Satoshi Yasuda,
  • Hidenori Toyoda,
  • Hideko Ohama,
  • Kazuhiro Nouso,
  • Akemi Tsutsui,
  • Takuya Nagano,
  • Norio Itokawa,
  • Korenobu Hayama,
  • Taeang Arai,
  • Michitaka Imai,
  • Yohei Koizumi,
  • Shinichiro Nakamura,
  • Kouji Joko,
  • Kojiro Michitaka,
  • Yoichi Hiasa,
  • Masatoshi Kudo

DOI
https://doi.org/10.1159/000513355

Abstract

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Background/Aim: An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD). Methods: From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], n = 26; continued LEN beyond PD [B group], n = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score. Results: Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, p < 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, p = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, p < 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, p = 0.004), appearance of new extrahepatic metastasis (HR 2.396, p = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, p < 0.001), and continuing LEN beyond PD (HR 0.297, p < 0.001). Conclusion: When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.

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