Lenvatinib radiofrequency ablation sequential therapy offers survival benefits for patients with unresectable hepatocellular carcinoma at intermediate stage and the liver reserve of Child-Pugh A category: A multicenter study

Ying Zhang; Kazushi Numata; Kento Imajo; Haruki Uojima; Akihiro Funaoka; Satoshi Komiyama; Katsuaki Ogushi; Makoto Chuma; Kuniyasu Irie; Shigehiro Kokubu; Masato Yoneda; Takashi Kobayashi; Hisashi Hidaka; Taito Fukushima; Satoshi Kobayashi; Manabu Morimoto; Tatehiro Kagawa; Nobuhiro Hattori; Tsunamasa Watanabe; Shigeru Iwase; Shin Maeda

doi:10.1111/hepr.14089

Lenvatinib radiofrequency ablation sequential therapy offers survival benefits for patients with unresectable hepatocellular carcinoma at intermediate stage and the liver reserve of Child-Pugh A category: A multicenter study

Hepatol Res. 2024 Jul 2. doi: 10.1111/hepr.14089. Online ahead of print.

Authors

Ying Zhang^{1

2

3}, Kazushi Numata¹, Kento Imajo^{4

5}, Haruki Uojima⁶, Akihiro Funaoka¹, Satoshi Komiyama¹, Katsuaki Ogushi¹, Makoto Chuma¹, Kuniyasu Irie², Shigehiro Kokubu⁴, Masato Yoneda⁷, Takashi Kobayashi⁷, Hisashi Hidaka⁶, Taito Fukushima⁸, Satoshi Kobayashi⁸, Manabu Morimoto⁸, Tatehiro Kagawa⁹, Nobuhiro Hattori¹⁰, Tsunamasa Watanabe¹⁰, Shigeru Iwase¹¹, Shin Maeda²

Affiliations

¹ Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.
² Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
³ Department of Medical Ultrasound, Ningbo Medical Center Lihuili Hospital, Ningbo, China.
⁴ Department of Gastroenterology, Shin-Yurigaoka General Hospital, Kawasaki, Japan.
⁵ Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan.
⁶ Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
⁷ Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
⁸ Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan.
⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
¹⁰ Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
¹¹ Department of Gastroenterology, Fujisawa City Hospital, Fujisawa, Japan.

PMID: 38953838
DOI: 10.1111/hepr.14089

Abstract

Aim: This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients.

Methods: One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy.

Results: After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin-bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186-0.782), 2.220 (95% CI, 1.410-3.493), and 0.982 (95% CI, 0.966-0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176-0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215-0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed.

Conclusion: Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy.

Keywords: hepatocellular carcinoma; lenvatinib RFA sequential therapy; overall survival; progression‐free survival; propensity score matching; radiofrequency ablation.