Lenvatinib, toripalimab, plus hepatic arterial infusion chemotherapy versus lenvatinib alone for advanced hepatocellular carcinoma

Min-Ke He, Run-Bin Liang, Yang Zhao, Yu-Jie Xu, Huan-Wei Chen, Yuan-Min Zhou, Zhi-Cheng Lai, Li Xu, Wei Wei, Yao-Jun Zhang, Min-Shan Chen, Rong-Ping Guo, Qi-Jiong Li, Ming Shi, Min-Ke He, Run-Bin Liang, Yang Zhao, Yu-Jie Xu, Huan-Wei Chen, Yuan-Min Zhou, Zhi-Cheng Lai, Li Xu, Wei Wei, Yao-Jun Zhang, Min-Shan Chen, Rong-Ping Guo, Qi-Jiong Li, Ming Shi

Abstract

Background: Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma, but prognosis is still unsatisfactory. Recently, hepatic arterial infusion chemotherapy (HAIC), and immune checkpoint inhibitors showed promising results for advanced hepatocellular carcinoma. Considering different anti-malignancy mechanisms, combining these three treatments may improve outcomes. This study aimed to compare the efficacy and safety of lenvatinib, toripalimab, plus HAIC versus lenvatinib for advanced hepatocellular carcinoma.

Methods: This was a retrospective study including patients treated with lenvatinib [8 mg (⩽60 kg) or 12 mg (>60 kg) once daily] or lenvatinib, toripalimab plus HAIC [LeToHAIC group, lenvatinib 0-1 week prior to initial HAIC, 240 mg toripalimab 0-1 day prior to every HAIC cycle, and HAIC with FOLFOX regimen (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 46 h, every 3 weeks)]. Progression-free survival, overall survival, objective response rate, and treatment-related adverse events were compared.

Results: From February 2019 to August 2019, 157 patients were included in this study: 71 in the LeToHAIC group and 86 in the lenvatinib group. The LeToHAIC group showed longer progression-free survival (11.1 versus 5.1 months, p < 0.001), longer overall survival (not reached versus 11 months, p < 0.001), and a higher objective response rate (RECIST: 59.2% versus 9.3%, p < 0.001; modified RECIST: 67.6% versus 16.3%, p < 0.001) than the lenvatinib group. In addition, 14.1% and 21.1% of patients in the LeToHAIC group achieved complete response of all lesions and complete response of the intrahepatic target lesions per modified RECIST criteria, respectively. Grade 3/4 treatment-related adverse events that were more frequent in the LeToHAIC group than in the lenvatinib group included neutropenia (8.5% versus 1.2%), thrombocytopenia (5.6% versus 0), and nausea (5.6% versus 0).

Conclusions: Lenvatinib, toripalimab, plus HAIC had acceptable toxic effects and might improve survival compared with lenvatinib alone in advanced hepatocellular carcinoma.

Keywords: FOLFOX; hepatic arterial infusion chemotherapy; hepatocellular carcinoma; lenvatinib; toripalimab.

Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

© The Author(s), 2021.

Figures

Figure 1.
Figure 1.
Patient selection flow. FOLFOX, oxaliplatin, 5-fluorouracil, and leucovorin; HAIC, hepatic arterial infusion chemotherapy; HCC, hepatocellular carcinoma.
Figure 2.
Figure 2.
Kaplan–Meier curves for progression-free survival (a) and overall survival (b). CI, confidence interval; HR, hazard ratio; LeToHAIC, lenvatinib, toripalimab plus hepatic arterial infusion chemotherapy.
Figure 3.
Figure 3.
Kaplan–Meier curves for progression-free survival (a, b) and overall survival (c, d) after stratification by the absence or presence of extrahepatic metastasis. CI, confidence interval; HR, hazard ratio; LeToHAIC, lenvatinib, toripalimab plus hepatic arterial infusion chemotherapy.
Figure 4.
Figure 4.
Best percentage changes from baseline in size of the intrahepatic target lesions of patients receiving lenvatinib, toripalimab plus hepatic arterial infusion chemotherapy. (a) Assessed with RECIST in patients with image measurements before and after treatment; (b) Assessed with mRECIST in patients with image measurements before and after treatment. mRECIST, modified Response Evaluation Criteria in Solid Tumors; RECIST, Response Evaluation Criteria in Solid Tumors.

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