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. 2022 Oct 16;14(20):5066.
doi: 10.3390/cancers14205066.

Analysis of Lenvatinib's Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma

Kei Amioka  1 , Tomokazu Kawaoka  1 , Takahiro Kinami  1 , Shintaro Yamasaki  1 , Masanari Kosaka  1 , Yusuke Johira  1 , Shigeki Yano  1 , Kensuke Naruto  1 , Yuwa Ando  1 , Yasutoshi Fujii  1 , Shinsuke Uchikawa  1 , Atsushi Ono  1 , Masami Yamauchi  1 , Michio Imamura  1 , Yumi Kosaka  2 , Kazuki Ohya  2 , Nami Mori  2 , Shintaro Takaki  2 , Keiji Tsuji  2 , Keiichi Masaki  3 , Yoji Honda  3 , Hirotaka Kouno  4 , Hioshi Kohno  4 , Kei Morio  5 , Takashi Moriya  5 , Noriaki Naeshiro  6 , Michihiro Nonaka  7 , Yasuyuki Aisaka  7 , Takahiro Azakami  8 , Akira Hiramatsu  8 , Hiroshi Aikata  1 , Shiro Oka  1
Affiliations

Analysis of Lenvatinib's Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma

Kei Amioka et al. Cancers (Basel). .

Abstract

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin-bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.

Keywords: LEN-TACE sequential therapy; hepatocellular carcinoma; intermediate stage; lenvatinib; modified Response Evaluation Criteria in Solid Tumors (mRECIST); overall survival; radiological response.

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Conflict of interest statement

Michio Imamura has received research funding from Bristol-Myers Squibb and AbbVie. Hiroshi Aikata has received honoraria from Eisai and Bayer. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Overall survival (OS) and progression-free survival (PFS) from the initiation of lenvatinib in the 140 patients included in this study. (a) OS from the initiation of lenvatinib (median survival time, 24.4 months). (b) PFS from the initiation of lenvatinib (median survival time, 9.0 months).
Figure 2
Figure 2
Comparison of overall survival (OS) and progression-free survival (PFS) by the response at the first, second, and best responses as evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST). (a) OS at the first response (objective response (OR) 34.4 months, non-OR 19.6 months, p = 0.007). (b) OS at the second response (OR not-reached, non-OR 21.1 months, p < 0.001). (c) OS at the best response (OR 34.4 months, non-OR 15.0 months, p < 0.001). (d) PFS at the first response (OR 11.0 months, non-OR 5.8 months, p = 0.001). (e) PFS at the second response (OR 14.0 months, non-OR 5.8 months, p < 0.001). (f) PFS at the best response (OR 11.6 months, non-OR 3.8 months, p < 0.001).
Figure 3
Figure 3
Comparison of overall survival (OS) and progression-free survival (PFS) by four factors, focusing on transarterial chemoembolization (TACE) in combination. (a) OS by the response at the first evaluation and TACE combination (objective response (OR)/with TACE not-reached, OR/without TACE 23.1 months, non-OR/with TACE 27.3 months, non-OR/without TACE 14.0 months, p < 0.001). (b) OS by up to seven criteria and TACE combination (up to seven criteria in/with TACE not-reached, up to seven criteria in/without TACE 25.5 months, up to seven criteria out/with TACE 45.0 months, up to seven criteria out/without TACE 17.6 months, p < 0.001). (c) OS by tumor morphology and TACE combination (simple nodular [SN]/with TACE not-reached, SN/without TACE 34.4 months, non-SN/with TACE 45.0 months, non-SN/without TACE 17.6 months, p < 0.001). (d) OS by modified albumin–bilirubin (mALBI) grade and TACE combination (mALBI 1–2a/with TACE not-reached, mALBI 1–2a/without TACE 24.4 months, mALBI 2b/with TACE 45.0 months, mALBI 2b/without TACE 17.4 months, p < 0.001). (e) PFS by the response at the first evaluation and TACE combination (OR/with TACE 14.0 months, OR/without TACE 10.7 months, non-OR/with TACE 10.8 months, non-OR/without TACE 3.5 months, p < 0.001). (f) PFS by up to seven criteria and TACE combination (up to seven criteria in/with TACE 24.3 months, up to seven criteria in/without TACE 11.0 months, up to seven criteria out/with TACE 10.8 months, up to seven criteria out/without TACE 5.4 months, p < 0.001). (g) PFS by mALBI grade and TACE combination (mALBI 1–2a/with TACE 12.6 months, mALBI 1–2a/without TACE 8.3 months, mALBI 2b/with TACE 10.5 months, mALBI 2b/without TACE 4.9 months, p < 0.001). (h) PFS by tumor morphology and TACE combination (SN/with TACE 10.8 months, SN/without TACE 9.4 months, non-SN/with TACE 12.6 months, non-SN/without TACE 5.8 months, p < 0.001).
Figure 4
Figure 4
Comparison of overall survival (OS) by conversion therapy.
See this image and copyright information in PMC

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