Subsequent locoregional therapy prolongs survival in progressive hepatocellular carcinoma patients under lenvatinib treatment

Po-Ting Lin; Wei Teng; Wen-Juei Jeng; Chen-Chun Lin; Chun-Yen Lin; Shi-Ming Lin; I-Shyan Sheen

doi:10.1016/j.jfma.2024.01.031

Subsequent locoregional therapy prolongs survival in progressive hepatocellular carcinoma patients under lenvatinib treatment

J Formos Med Assoc. 2024 Feb 2:S0929-6646(24)00084-6. doi: 10.1016/j.jfma.2024.01.031. Online ahead of print.

Authors

Po-Ting Lin¹, Wei Teng², Wen-Juei Jeng³, Chen-Chun Lin⁴, Chun-Yen Lin⁵, Shi-Ming Lin⁶, I-Shyan Sheen⁷

Affiliations

¹ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan. Electronic address: linpoting0101@gmail.com.
² Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan. Electronic address: b101090023@gmail.com.
³ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan. Electronic address: Rachel.jeng@gmail.com.
⁴ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan. Electronic address: lincc53@gmail.com.
⁵ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan. Electronic address: chunyenlin@gmail.com.
⁶ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan. Electronic address: lsmpaicyto@gmail.com.
⁷ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan. Electronic address: happy95kevin@gmail.com.

PMID: 38310071
DOI: 10.1016/j.jfma.2024.01.031

Abstract

Background: Locoregional therapy and multi-kinase inhibitor agent have been the backbone of treatment for hepatocellular carcinoma (HCC) patients. However, the effect of combination or sequential use of locoregional therapy on HCC patients receiving multi-kinase inhibitor remain uncertain. Therefore, we aim to explore whether the subsequent locoregional therapy provides better survival in HCC patients under lenvatinib treatment.

Methods: From March 2018 to April 2020, a total of 78 unresectable HCC patients receiving lenvatinib were recruited. Image response was evaluated by dynamic image using the modified RECIST criteria. Among patients with tumor progression under lenvatinib treatment, whether receiving subsequent locoregional therapy or not were documented. Overall survival between two groups and the predictors for tumor progression were also analyzed.

Results: Among the 78 patients receiving lenvatinib, the median age was 67.8 years old, and 69.2 % were male. Forty-four patients (56.4 %) experienced tumor progression with time to progression 5.1 months (95 % confidence interval (CI): 4.7-6.8) months. In multivariable Cox regression analysis, albumin-bilirubin (ALBI) grade II (adjusted HR: 2.883, P = 0.0104), and treatment duration less than three months (adjusted HR: 3.801, P = 0.0014) were the independent predictive factors for tumor progression, while patients achieving objective response under lenvatinib treatment within 12 weeks was the independent protective factor for tumor progression (adjusted HR: 0.144, P = 0.0020). Among the 44 patients with tumor progression, twenty-six (59.1 %) patients received subsequent locoregional therapy after tumor progression. Comparing to those with tumor progression without locoregional treatment, patients who received subsequent locoregional therapy had significantly better survival (1st year cumulative survival rate 70 % vs 27 %, log-rank P = 0.003).

Conclusion: ALBI grade, treatment duration of lenvatinib, and achieving objective image response within twelve weeks were the independent predictive factors for tumor progression. Furthermore, longer overall survival was observed in tumor progression patients with subsequent locoregional therapy and with better liver preserved function.

Keywords: Lenvatinib; Radiofrequency ablation; Survival; Systemic therapy; Transarterial chemoembolization.