Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma

Maesaka, Kazuki; Hikita, Hayato; Tahata, Yuki; Nishioka, Chinatsu; Kai, Machiko; Shirai, Kumiko; Murai, Kazuhiro; Makino, Yuki; Saito, Yoshinobu; Kodama, Takahiro; Ohkawa, Kazuyoshi; Miyazaki, Masanori; Nozaki, Yasutoshi; Yakushijin, Takayuki; Sakamori, Ryotaro; Tatsumi, Nobuyuki; Matsumoto, Kengo; Ishida, Hisashi; Iio, Sadaharu; Nawa, Takatoshi; Kakita, Naruyasu; Nakahara, Masanori; Hosui, Atsushi; Yoshida, Yuichi; Usui, Takeo; Imanaka, Kazuho; Doi, Yoshinori; Sakakibara, Mitsuru; Takehara, Tetsuo

doi:https://doi.org/10.1007/s00535-025-02308-x

Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma

Maesaka, Kazuki; Hikita, Hayato; Tahata, Yuki et al.

Journal of Gastroenterology, 2025

Number of Access:14（2025-12-05 11:18 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/103018

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Title	Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma
Creator	NRID 1000080974857 1000080974857 ORCID 0009-0007-5642-9470 0009-0007-5642-9470 researchmap permalink maesaka maesaka Scopus Author ID 57205239322 57205239322 CreatorName Maesaka, Kazuki
	NRID 1000020623044 1000020623044 ORCID 0000-0003-2488-7315 0000-0003-2488-7315 researchmap permalink hikitahayato hikitahayato Scopus Author ID 23667454900 23667454900 CreatorName Hikita, Hayato
	NRID 1000000838047 1000000838047 ORCID 0000-0002-9116-7054 0000-0002-9116-7054 researchmap permalink yuki.tahata yuki.tahata Scopus Author ID 56755390400 56755390400 CreatorName Tahata, Yuki
	CreatorName Nishioka, Chinatsu
	CreatorName Kai, Machiko
	NRID 1000020992267 1000020992267 researchmap permalink u987841f u987841f CreatorName Shirai, Kumiko
	NRID 1000050867314 1000050867314 ORCID 0000-0001-8634-2922 0000-0001-8634-2922 researchmap permalink murai_kazuhiro murai_kazuhiro Scopus Author ID 57202460806 57202460806 CreatorName Murai, Kazuhiro
	NRID 1000060771334 1000060771334 researchmap permalink yuki-makino yuki-makino Scopus Author ID 41561612200 41561612200 CreatorName Makino, Yuki
	NRID 1000060814598 1000060814598 ORCID 0000-0002-0624-0449 0000-0002-0624-0449 researchmap permalink saito_yoshinobu saito_yoshinobu Scopus Author ID 55912459300 55912459300 CreatorName Saito, Yoshinobu
	NRID 1000010623275 1000010623275 ORCID 0000-0002-6250-1324 0000-0002-6250-1324 researchmap permalink takahirokodama takahirokodama Scopus Author ID 35193885800 35193885800 CreatorName Kodama, Takahiro
	NRID 1000080432540 1000080432540 CreatorName Ohkawa, Kazuyoshi
	CreatorName Miyazaki, Masanori
	CreatorName Nozaki, Yasutoshi
	CreatorName Yakushijin, Takayuki
	NRID 1000010644685 1000010644685 CreatorName Sakamori, Ryotaro
	CreatorName Tatsumi, Nobuyuki
	CreatorName Matsumoto, Kengo
	NRID 1000000506230 1000000506230 CreatorName Ishida, Hisashi
	CreatorName Iio, Sadaharu
	CreatorName Nawa, Takatoshi
	CreatorName Kakita, Naruyasu
	CreatorName Nakahara, Masanori
	NRID 1000010536882 1000010536882 CreatorName Hosui, Atsushi
	CreatorName Yoshida, Yuichi
	CreatorName Usui, Takeo
	CreatorName Imanaka, Kazuho
	CreatorName Doi, Yoshinori
	CreatorName Sakakibara, Mitsuru
	NRID 1000070335355 1000070335355 CreatorName Takehara, Tetsuo
Subject	Atezolizumab plus bevacizumab
	Lenvatinib
	Propensity score matching
Description	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00535-025-02308-x
Abstract	Background: Lenvatinib is widely used in hepatocellular carcinoma (HCC), but its efficacy following atezolizumab plus bevacizumab remains unclear. This study compared the therapeutic impact of lenvatinib administered after immunotherapy, following its use as a first-line systemic therapy. Methods: This retrospective study analyzed patients with unresectable HCC who received lenvatinib either after atezolizumab plus bevacizumab as second-line therapy or as first-line therapy. Propensity score matching (PSM) was applied to balance baseline characteristics. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared. Results: Following PSM, 63 matched pairs were analyzed. The “After Atezo + Beva” group had larger and more advanced intrahepatic tumors, but PSM balanced the groups’ baseline characteristics. Based on mRECIST, the objective response rate and disease control rate were 41.1% and 80.4% in the “After Atezo + Beva” group, and 49.2% and 76.3% in the first-line group. Based on RECIST version 1.1, these were 25.0% and 80.4% vs. 28.8% and 76.3%, respectively. Median PFS was 4.5 vs. 5.2 months (p = 0.233) and median OS was 14.3 vs. 16.0 months (p = 0.769). Grades ≥ 3 AEs occurred more frequently in the “After Atezo + Beva” group (74.9% vs. 50.8%, p = 0.006), with grades ≥ 3 proteinuria in 31.7% vs. 14.3% (p = 0.020) and grades ≥ 3 fatigue in 12.7% vs. 1.6% (p = 0.033). Conclusions: Lenvatinib demonstrated comparable efficacy whether used following atezolizumab plus bevacizumab or as first-line therapy in unresectable HCC. These findings support its clinical utility in the post-immune checkpoint inhibitor setting, with attention to AE management.
Publisher	Springer
Source Title	Journal of Gastroenterology
Date of Issued	2025-10-25
Language	English
Handle URL	https://hdl.handle.net/11094/103018
PISSN	09441174
eISSN	14355922
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1007/s00535-025-02308-x
Access Rights	embargoed access
CopyRight	Maesaka K., Hikita H., Tahata Y., et al. Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma. Journal of Gastroenterology (2025); https://doi.org/10.1007/s00535-025-02308-x.
CopyRight	The full-text file will be made open to the public on 25 October 2026 in accordance with the publisher's policy.
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Gastroenterology. 2025
DC.title	Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma
DC.creator	Maesaka, Kazuki
	Hikita, Hayato
	Tahata, Yuki
	Nishioka, Chinatsu
	Kai, Machiko
	Shirai, Kumiko
	Murai, Kazuhiro
	Makino, Yuki
	Saito, Yoshinobu
	Kodama, Takahiro
	Ohkawa, Kazuyoshi
	Miyazaki, Masanori
	Nozaki, Yasutoshi
	Yakushijin, Takayuki
	Sakamori, Ryotaro
	Tatsumi, Nobuyuki
	Matsumoto, Kengo
	Ishida, Hisashi
	Iio, Sadaharu
	Nawa, Takatoshi
	Kakita, Naruyasu
	Nakahara, Masanori
	Hosui, Atsushi
	Yoshida, Yuichi
	Usui, Takeo
	Imanaka, Kazuho
	Doi, Yoshinori
	Sakakibara, Mitsuru
	Takehara, Tetsuo
DC.publisher	Springer
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-10-25
DC.identifier	https://doi.org/10.1007/s00535-025-02308-x
DC.subject	Atezolizumab plus bevacizumab
	Lenvatinib
	Propensity score matching
DC.description	This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00535-025-02308-x
DCTERMS.abstract	Background: Lenvatinib is widely used in hepatocellular carcinoma (HCC), but its efficacy following atezolizumab plus bevacizumab remains unclear. This study compared the therapeutic impact of lenvatinib administered after immunotherapy, following its use as a first-line systemic therapy. Methods: This retrospective study analyzed patients with unresectable HCC who received lenvatinib either after atezolizumab plus bevacizumab as second-line therapy or as first-line therapy. Propensity score matching (PSM) was applied to balance baseline characteristics. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared. Results: Following PSM, 63 matched pairs were analyzed. The “After Atezo + Beva” group had larger and more advanced intrahepatic tumors, but PSM balanced the groups’ baseline characteristics. Based on mRECIST, the objective response rate and disease control rate were 41.1% and 80.4% in the “After Atezo + Beva” group, and 49.2% and 76.3% in the first-line group. Based on RECIST version 1.1, these were 25.0% and 80.4% vs. 28.8% and 76.3%, respectively. Median PFS was 4.5 vs. 5.2 months (p = 0.233) and median OS was 14.3 vs. 16.0 months (p = 0.769). Grades ≥ 3 AEs occurred more frequently in the “After Atezo + Beva” group (74.9% vs. 50.8%, p = 0.006), with grades ≥ 3 proteinuria in 31.7% vs. 14.3% (p = 0.020) and grades ≥ 3 fatigue in 12.7% vs. 1.6% (p = 0.033). Conclusions: Lenvatinib demonstrated comparable efficacy whether used following atezolizumab plus bevacizumab or as first-line therapy in unresectable HCC. These findings support its clinical utility in the post-immune checkpoint inhibitor setting, with attention to AE management.
DC.rights	Maesaka K., Hikita H., Tahata Y., et al. Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma. Journal of Gastroenterology (2025); https://doi.org/10.1007/s00535-025-02308-x.
DC.rights	The full-text file will be made open to the public on 25 October 2026 in accordance with the publisher's policy.
DC.format	103018
citation_title	Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma
citation_author	Maesaka, Kazuki
	Hikita, Hayato
	Tahata, Yuki
	Nishioka, Chinatsu
	Kai, Machiko
	Shirai, Kumiko
	Murai, Kazuhiro
	Makino, Yuki
	Saito, Yoshinobu
	Kodama, Takahiro
	Ohkawa, Kazuyoshi
	Miyazaki, Masanori
	Nozaki, Yasutoshi
	Yakushijin, Takayuki
	Sakamori, Ryotaro
	Tatsumi, Nobuyuki
	Matsumoto, Kengo
	Ishida, Hisashi
	Iio, Sadaharu
	Nawa, Takatoshi
	Kakita, Naruyasu
	Nakahara, Masanori
	Hosui, Atsushi
	Yoshida, Yuichi
	Usui, Takeo
	Imanaka, Kazuho
	Doi, Yoshinori
	Sakakibara, Mitsuru
	Takehara, Tetsuo
citation_publisher	Springer
citation_language	English
citation_date	2025-10-25
citation_journal_title	Journal of Gastroenterology
citation_doi	https://doi.org/10.1007/s00535-025-02308-x
citation_public_url	https://hdl.handle.net/11094/103018

Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma

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