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

アクセス数:14件（2025-12-05 06:37 集計）

固定URL: https://hdl.handle.net/11094/103018

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JGastroenterol	pdf	なし	215 KB	2026.10.25
JGastroenterol_Figs	pdf	なし	754 KB	2026.10.25	Figures
JGastroenterol_Sup_Figs	pdf	なし	913 KB	2026.10.25	Supplementary Figures
JGastroenterol_Sup_Tabs	pdf	なし	116 KB	2026.10.25	Supplementary Tables

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タイトル	Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma
著者	NRID 1000080974857 1000080974857 ORCID 0009-0007-5642-9470 0009-0007-5642-9470 researchmap permalink maesaka maesaka Scopus Author ID 57205239322 57205239322 著者名 Maesaka, Kazuki
	NRID 1000020623044 1000020623044 ORCID 0000-0003-2488-7315 0000-0003-2488-7315 researchmap permalink hikitahayato hikitahayato Scopus Author ID 23667454900 23667454900 著者名 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 著者名 Tahata, Yuki
	著者名 Nishioka, Chinatsu
	著者名 Kai, Machiko
	NRID 1000020992267 1000020992267 researchmap permalink u987841f u987841f 著者名 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 著者名 Murai, Kazuhiro
	NRID 1000060771334 1000060771334 researchmap permalink yuki-makino yuki-makino Scopus Author ID 41561612200 41561612200 著者名 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 著者名 Saito, Yoshinobu
	NRID 1000010623275 1000010623275 ORCID 0000-0002-6250-1324 0000-0002-6250-1324 researchmap permalink takahirokodama takahirokodama Scopus Author ID 35193885800 35193885800 著者名 Kodama, Takahiro
	NRID 1000080432540 1000080432540 著者名 Ohkawa, Kazuyoshi
	著者名 Miyazaki, Masanori
	著者名 Nozaki, Yasutoshi
	著者名 Yakushijin, Takayuki
	NRID 1000010644685 1000010644685 著者名 Sakamori, Ryotaro
	著者名 Tatsumi, Nobuyuki
	著者名 Matsumoto, Kengo
	NRID 1000000506230 1000000506230 著者名 Ishida, Hisashi
	著者名 Iio, Sadaharu
	著者名 Nawa, Takatoshi
	著者名 Kakita, Naruyasu
	著者名 Nakahara, Masanori
	NRID 1000010536882 1000010536882 著者名 Hosui, Atsushi
	著者名 Yoshida, Yuichi
	著者名 Usui, Takeo
	著者名 Imanaka, Kazuho
	著者名 Doi, Yoshinori
	著者名 Sakakibara, Mitsuru
	NRID 1000070335355 1000070335355 著者名 Takehara, Tetsuo
キーワード等	Atezolizumab plus bevacizumab
	Lenvatinib
	Propensity score matching
内容	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
抄録	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.
出版者	Springer
収録物名	Journal of Gastroenterology
刊行年月	2025-10-25
言語	英語
ハンドルURL	https://hdl.handle.net/11094/103018
PISSN	09441174
eISSN	14355922
関連情報 (isVersionOf)	DOI (出版社版) https://doi.org/10.1007/s00535-025-02308-x
アクセス権	embargoed access
権利情報	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.
権利情報	The full-text file will be made open to the public on 25 October 2026 in accordance with the publisher's policy.
出版タイプ	Accepted Manuscript
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	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	英語
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	英語
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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