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The combination treatment strategy of lenvatinib for hepatocellular carcinoma: a real-world study

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Abstract

Purpose

Lenvatinib is recommended as a first-line therapy in unresectable hepatocellular carcinoma (HCC). Combination therapy with local therapy (LT) or PD-1/PD-L1 inhibitors (PI) might improve the antitumor effect of lenvatinib. The objective of this study was to investigate the antitumor effect of lenvatinib-based combination therapies.

Methods

The study retrospectively analyzed 215 HCC patients who received lenvatinib therapy. The outcomes of patients treated with lenvatinib monotherapy as well as combination strategies were compared. Progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 was the primary endpoint, while PFS by mRECIST, overall survival (OS), objective response rate (ORR) and safety were the secondary endpoints. Propensity score matching (PSM) analysis was performed to overcome the bias of baseline characteristics.

Results

Compared with lenvatinib monotherapy, combination therapy prolonged PFS (by RECIST v1.1, 7.77 vs. 4.43 months, P = 0.045; by mRECIST, 6.97 vs. 5.27 months, P = 0.067). A higher ORR was also recorded in the combined-therapy group, according to both RECIST v1.1 (37 vs. 5%, P < 0.001) and mRECIST (53 vs. 11%, P < 0.001). Similar outcomes were obtained after PSM. Moreover, triple therapy (combined with both PI and LT) was significantly superior to dual therapy (combined with either PI or LT) in terms of better PFS according to RECIST v1.1 (8.90 vs. 6.43 months, P = 0.023). However, adverse events occurred in more patients receiving combined therapy and triple therapy. No difference was observed in OS between groups.

Conclusion

Combination therapies based on lenvatinib were associated with significantly better PFS and tumor response rates than lenvatinib monotherapy in HCC patients.

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Data availability

The data that support the findings of this study are openly available in Research Data Deposit at https://www.researchdata.org.cn/default.aspx, after publication.

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Funding

This work was funded by the National Key R&D Program of China (2020YFE0202200) and the National Natural Science Foundation of China (81772589).

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Author notes

  1. Jinbin Chen, Peiyao Xiong and Man Nie have contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China

    Jinbin Chen, Peiyao Xiong, Man Nie, Yangxun Pan, Juncheng Wang, Dandan Hu, Zhongguo Zhou, Yaojun Zhang, Minshan Chen & Li Xu

  2. Department of Liver Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, 510060, Guangdong, China

    Jinbin Chen, Peiyao Xiong, Yangxun Pan, Juncheng Wang, Dandan Hu, Zhongguo Zhou, Yaojun Zhang, Minshan Chen & Li Xu

  3. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China

    Man Nie

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  1. Jinbin Chen
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Contributions

JC, PX and MN equally contributed to this work. Conception and design: MC and LX; Acquisition of data: JC, PX, YP and JW; Data analysis and interpretation: JC, MN, YZ and ZZ; Manuscript writing: JC, PX and MN; Manuscript review and editing: DH, MC and LX; Final approval of manuscript: all authors.

Corresponding author

Correspondence to Li Xu.

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Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval

This study was conducted ethically in accordance with the World Medical Association Declaration of Helsinki and approved by the Institutional Review Board of Sun Yat-sen University Cancer Center (Approval number: B2017-088-01).

Consent to participate

This study was conducted ethically in accordance with the World Medical Association Declaration of Helsinki, and all included subjects signed informed consent forms.

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Informed consent was obtained from all individual participants included in this study. No identifiable personal data from recruited patients were included in this article.

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Chen, J., Xiong, P., Nie, M. et al. The combination treatment strategy of lenvatinib for hepatocellular carcinoma: a real-world study. J Cancer Res Clin Oncol 149, 2491–2500 (2023). https://doi.org/10.1007/s00432-022-04082-2

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  • DOI: https://doi.org/10.1007/s00432-022-04082-2

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